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The decays 𝜒𝑐𝐽→Σ0¯𝑝𝐾++c.c. (𝐽=0,1,2) are studied via the radiative transition 𝜓(3686)→𝛾𝜒𝑐𝐽 based on a data sample of (448.1±2.9)×106 𝜓(3686) events collected with the BESIII detector. The branching fractions of 𝜒𝑐𝐽→Σ0¯𝑝𝐾++c.c. (𝐽=0,1,2) are measured to be (3.03±0.12±0.15)×10−4, (1.46±0.07±0.07)×10−4, and (0.91±0.06±0.05)×10−4, respectively, where the first uncertainties are statistical and the second are systematic. In addition, no evident structure is found for excited baryon resonances on the two-body subsystems with the limited statistics.
The Born cross sections and effective form factors of the process e+e−→ΛΣ¯0+c.c. are measured at 14 center-of-mass energy points from 2.3094 to 3.0800 GeV, based on data corresponding to an integrated luminosity of (478.5±4.8) pb−1 collected with the BESIII detector. A non-zero Born cross section is observed at the center-of-mass energy of 2.3094 GeV with a statistical significance of more than five standard deviations, and the cross sections at other energies are obtained with improved precision compared to earlier measurements from the BaBar Collaboration. The Born cross-section lineshape is described better by a shape with a plateau near the threshold than by a pQCD motivated functional form.
Using a dataset of 6.32 fb−1 of 𝑒+𝑒− annihilation data collected with the BESIII detector at center-of-mass energies between 4178 and 4226 MeV, we have measured the absolute branching fraction of the leptonic decay 𝐷+𝑠→𝜏+𝜈𝜏 via 𝜏+→𝑒+𝜈𝑒¯𝜈𝜏, and find ℬ𝐷+𝑠→𝜏+𝜈𝜏=(5.27±0.10±0.12)×10−2, where the first uncertainty is statistical and the second is systematic. The precision is improved by a factor of 2 compared to the previous best measurement. Combining with 𝑓𝐷+𝑠 from lattice quantum chromodynamics calculations or the |𝑉𝑐𝑠| from the CKMfitter group, we extract |𝑉𝑐𝑠|=0.978±0.009±0.012 and 𝑓𝐷+𝑠=(251.1±2.4±3.0) MeV, respectively. Combining our result with the world averages of ℬ𝐷+𝑠→𝜏+𝜈𝜏 and ℬ𝐷+𝑠→𝜇+𝜈𝜇, we obtain the ratio of the branching fractions ℬ𝐷+𝑠→𝜏+𝜈𝜏/ℬ𝐷+𝑠→𝜇+𝜈𝜇=9.72±0.37, which is consistent with the standard model prediction of lepton flavor universality.
The first observation of the decays J/ψ→p¯Σ+K0S and J/ψ→pΣ¯−K0S is reported using (10087±44)×106 J/ψ events recorded by the BESIII detector at the BEPCII storage ring. The branching fractions of each channel are determined to be B(J/ψ→p¯Σ+K0S)=(1.361±0.006±0.025)×10−4 and B(J/ψ→pΣ¯−K0S)=(1.352±0.006±0.025)×10−4. The combined result is B(J/ψ→p¯Σ+K0S+c.c.)=(2.725±0.009±0.050)×10−4, where the first uncertainty is statistical and the second systematic. The results presented are in good agreement with the branching fractions of the isospin partner decay J/ψ→pK−Σ¯0+c.c..
Using a sample of (27.12±0.14)×108 ψ(3686) events collected with the BESIII detector, the decay ψ(3686)→ΛΛ¯η′ with η′ subsequently decaying into γπ+π− and ηπ+π− is observed for the first time. The branching fraction of ψ(3686)→ΛΛ¯η′ is measured to be (7.34±0.94(stat.)±0.43(sys.))×10−6. No resonant structures are evident in the Λη′, Λ¯η′ and ΛΛ¯ mass spectra.
he absolute branching fraction of Λ→pμ−ν¯μ is reported for the first time based on an e+e− annihilation sample of ten billion J/ψ events collected with the BESIII detector at s√=3.097 GeV. The branching fraction is determined to be B(Λ→pμ−ν¯μ)=[1.48±0.21(stat)±0.08(syst)]×10−4, which is a significant improvement in precision over the previous indirect measurements. Combining this result with the world average of B(Λ→pe−ν¯e), we obtain the ratio, Γ(Λ→pμ−ν¯μ)Γ(Λ→pe−ν¯e), to be 0.178±0.028, which agrees with the standard model prediction assuming lepton flavor universality. The asymmetry of the branching fractions of Λ→pμ−ν¯μ and Λ¯→p¯μ+νμ is also determined, and no evidence for CP violation is found.
Using an electron-positron collision data sample corresponding to an integrated luminosity of 2.93~fb−1 collected with the BESIII detector at a center-of-mass energy of 3.773 GeV, we search for the baryon and lepton number violating decays D0→p¯e+ and D0→pe−. No obvious signals are found with the current statistics. The upper limits on the branching fractions for D0→p¯e+ and D0→pe− are set to be 1.2×10−6 and 2.2×10−6 at 90\% confidence level, respectively.
Measurement of the absolute branching fraction of the singly Cabibbo suppressed decay Λc⁺ → pη′
(2022)
The singly Cabibbo suppressed decay Λ+c→pη′ is measured using 4.5 fb−1 of e+e− collision data collected at center-of-mass energies between 4.600 and 4.699 GeV with the BESIII detector at BEPCII. Evidence for Λ+c→pη′ with a statistical significance of 3.6σ is reported with a double-tag approach. The Λ+c→pη′ absolute branching fraction is determined to be (5.62+2.46−2.04±0.26)×10−4, where the first and second uncertainties are statistical and systematic, respectively. Our result is consistent with the branching fraction obtained by the Belle collaboration within the uncertainty of 1σ.
Measurement of e⁺e⁻ → ΛΛ¯η from 3.5106 to 4.6988 GeV and study of ΛΛ¯ mass threshold enhancement
(2023)
Using data samples with a total integrated luminosity of approximately 18 fb−1 collected by the BESIII detector operating at the BEPCII, the process e+e−→ΛΛ¯η is studied at center-of-mass energies between 3.5106 and 4.6988 GeV. The Born cross section for the process e+e−→ΛΛ¯η is measured. No significant structure is observed in the Born cross section line shape. An enhancement near the ΛΛ¯ mass threshold is observed for the first time in the process. The structure can be described by an S-wave Breit-Wigner function. Neglecting contribution of excited Λ states and potential interferences, the mass and width are determined to be (2356±7±17) MeV/c2 and (304±28±54) MeV, respectively, where the first uncertainties are statistical and the second are systematic.
Based on e+e− collision data corresponding to an integrated luminosity of 4.5 fb−1 collected at the center-of-mass energies between 4.600 and 4.699 GeV with the BESIII detector at BEPCII, the absolute branching fraction of the inclusive decay Λ+c→n+X, where X refers to any possible final state particles, is measured. The absolute branching fraction is determined to be B(Λ+c→n+X)=(32.4±0.7±1.5)%, where the first uncertainty is statistical and the second systematic. Assuming CP symmetry, the measurement indicates that about one-fourth of Λ+c (Λ¯−c) decay modes with a neutron (an anti-neutron) in the final state have not been observed.
We report on a comparison of two possible Λ+c spin hypotheses, J=12 and 32, via the process e+e−→Λ+cΛ¯−c, using the angular distributions of Λ+c decays into pK0S, Λπ+, Σ0π+, and Σ+π0. The data were recorded at s√=4.6 GeV with the BESIII detector and correspond to an integrated luminosity of 587 pb−1. The Λ+c spin is determined to be J=12, with this value favored over the 32 hypothesis with a significance corresponding to more than 6 Gaussian standard deviations.
A search has been performed for the semileptonic decays D0→K0SK−e+νe, D+→K0SK0Se+νe and D+→K+K−e+νe, using 7.9 fb−1 of e+e− annihilation data collected at the center-of-mass energy s√=3.773 GeV by the BESIII detector operating at the BEPCII collider. No significant signals are observed, and upper limits are set at the 90\% confidence level of 2.13×10−5, 1.54×10−5 and 2.10×10−5 for the branching fractions of D0→K0SK−e+νe, D+→K0SK0Se+νe and D+→K+K−e+νe, respectively.
The cross sections of the process e+e−→K0SK0L are measured at fifteen center-of-mass energies s√ from 2.00 to 3.08 GeV with the BESIII detector at the Beijing Electron Positron Collider (BEPCII). The results are found to be consistent with those obtained by BaBar. A resonant structure around 2.2 GeV is observed, with a mass and width of 2273.7±5.7±19.3 MeV/c2 and 86±44±51 MeV, respectively, where the first uncertainties are statistical and the second ones are systematic. The product of its radiative width (Γe+e−) with its branching fraction to K0SK0L (BrK0SK0L) is 0.9±0.6±0.7 eV.
Based on 14.7 fb−1 of e+e− annihilation data collected with the BESIII detector at the BEPCII collider at 17 different center-of-mass energies between 3.7730 GeV and 4.5995 GeV, Born cross sections of the two processes e+e−→pp¯η and e+e−→pp¯ω are measured for the first time. No indication of resonant production through a vector state V is observed, and upper limits on the Born cross sections of e+e−→V→pp¯η and e+e−→V→pp¯ω at the 90% confidence level are calculated for a large parameter space in resonance masses and widths. For the current world average parameters of the ψ(4230) of m=4.2187 GeV/c2 and Γ=44 MeV, we find upper limits on resonant production of the pp¯η and pp¯ω final states of 7.5 pb and 10.4 pb at the 90% CL, respectively.
Based on a sample of (448.1±2.9)×106 ψ(3686) events collected with the BESIII detector at BEPCII, the decays of ψ(3686)→K−ΛΞ¯¯¯¯++c.c. with Ξ¯¯¯¯+→Λ¯¯¯¯π+, Λ¯¯¯¯→p¯¯¯π+ are this http URL excited hyperons, Ξ(1690)− and Ξ(1820)−, are observed with large significance (≫10σ) in the K−Λ invariant mass distributions. A partial wave analysis is performed, and the spin-parities of Ξ(1690)− and Ξ(1820)− are determined to be 12− and 32−, respectively. The masses, widths, and product branching fractions of Ξ(1690)− and Ξ(1820)− are also measured.
Based on a sample of (448.1±2.9)×106 ψ(3686) events collected with the BESIII detector at BEPCII, the decays of ψ(3686)→K−ΛΞ¯¯¯¯++c.c. with Ξ¯¯¯¯+→Λ¯¯¯¯π+, Λ¯¯¯¯→p¯¯¯π+ are this http URL excited hyperons, Ξ(1690)− and Ξ(1820)−, are observed with large significance (≫10σ) in the K−Λ invariant mass distributions. A partial wave analysis is performed, and the spin-parities of Ξ(1690)− and Ξ(1820)− are determined to be 12− and 32−, respectively. The masses, widths, and product branching fractions of Ξ(1690)− and Ξ(1820)− are also measured.
The process e+e−→D∗+sD∗−s is studied with a semi-inclusive method using data samples at center-of-mass energies from threshold to 4.95 GeV collected with the BESIII detector operating at the Beijing Electron Positron Collider. The Born cross sections of the process are measured for the first time with high precision in this energy region. Two resonance structures are observed in the energy-dependent cross sections around 4.2 and 4.4 GeV. By fitting the cross sections with a coherent sum of three Breit-Wigner amplitudes and one phase-space amplitude, the two significant structures are assigned masses of (4186.5±9.0±30) MeV/c2 and (4414.5±3.2±6.0) MeV/c2, widths of (55±17±53) MeV and (122.6±7.0±8.2) MeV, where the first errors are statistical and the second ones are systematic. The inclusion of a third Breit-Wigner amplitude is necessary to describe a structure around 4.79 GeV.
Using e+e− collision data corresponding to a total integrated luminosity of 12.9 fb−1 collected with the BESIII detector at the BEPCII collider, the exclusive Born cross sections and the effective form factors of the reaction e+e−→Ξ−Ξ¯+ are measured via the single baryon-tag method at 23 center-of-mass energies between 3.510 and 4.843 GeV. Evidence for the decay ψ(3770)→Ξ−Ξ¯+ is observed with a significance of 4.5σ by analyzing the measured cross sections together with earlier BESIII results. For the other charmonium(-like) states ψ(4040), ψ(4160), Y(4230), Y(4360), ψ(4415), and Y(4660), no significant signal of their decay to Ξ−Ξ¯+ is found. For these states, upper limits of the products of the branching fraction and the electronic partial width at the 90% confidence level are provided.
The process e+e−→D∗+sD∗−s is studied with a semi-inclusive method using data samples at center-of-mass energies from threshold to 4.95 GeV collected with the BESIII detector operating at the Beijing Electron Positron Collider. The Born cross sections of the process are measured for the first time with high precision in this energy region. Two resonance structures are observed in the energy-dependent cross sections around 4.2 and 4.4 GeV. By fitting the cross sections with a coherent sum of three Breit-Wigner amplitudes and one phase-space amplitude, the two significant structures are assigned masses of (4186.5±9.0±30) MeV/c2 and (4414.5±3.2±6.0) MeV/c2, widths of (55±17±53) MeV and (122.6±7.0±8.2) MeV, where the first errors are statistical and the second ones are systematic. The inclusion of a third Breit-Wigner amplitude is necessary to describe a structure around 4.79 GeV.
Using (447.9 ± 2.3) million ψ(3686) events collected with the BESIII detector, the decays of χcJ→ϕϕ (J=0, 1, 2) have been studied via the decay ψ(3686)→γχcJ. The branching fractions of the decays χcJ→ϕϕ (J=0, 1, 2) are determined to be (8.48±0.26±0.27)×10−4, (4.36±0.13±0.18)×10−4, and (13.36±0.29±0.49)×10−4, respectively, which are the most precise measurements to date. From a helicity amplitude analysis of the process ψ(3686)→γχcJ,χcJ→ϕϕ,ϕ→K+K−, the polarization parameters of the χcJ→ϕϕ decays are determined for the first time.
Background: The faunal and floral relationship of northward-drifting India with its neighboring continents is of general biogeographic interest as an important driver of regional biodiversity. However, direct biogeographic connectivity of India and Southeast Asia during the Cenozoic remains largely unexplored. We investigate timing, direction and mechanisms of faunal exchange between India and Southeast Asia, based on a molecular phylogeny, molecular clock-derived time estimates and biogeographic reconstructions of the Asian freshwater crab family Gecarcinucidae. Results: Although the Gecarcinucidae are not an element of an ancient Gondwana fauna, their subfamily Gecarcinucinae, and probably also the Liotelphusinae, evolved on the Indian Subcontinent and subsequently dispersed to Southeast Asia. Estimated by a model testing approach, this dispersal event took place during the Middle Eocene, and thus before the final collision of India and the Tibet-part of Eurasia. Conclusions: We postulate that the India and Southeast Asia were close enough for exchange of freshwater organisms during the Middle Eocene, before the final Indian--Eurasian collision. Our data support geological models that assume the Indian plate having tracked along Southeast Asia during its move northwards.
Currently, the genus Polypedates comprises 26 species distributed in South, Southeast, and East Asia. Because of their relatively low dispersal capability and intolerance to seawater, this genus is ideal for the study of terrestrial range evolution that extends into the island archipelagos of southeastern Asia. In this study, based on data compiled for Polypedates from previous studies and partial mitochondrial and nuclear genes collected in this study, we performed systematic biogeographical analysis. We confirmed a Sundaland origin for the extant genus and showed northward dispersal into mainland Southeast Asia and Asia, which coincided with the timing of paleoclimatic change from the Oligocene to Middle Miocene. Climate fluctuations had a profound impact on species diversification within the genus Polypedates. Furthermore, the Red River did not mediate species exchange between Southeast Asia and mainland Asia until the end of the Miocene, with the sudden onset of northward dispersal in several clades independently at that time. Alternatively, the lineage of widespread insular P. leucomystax strongly supports the hypothesis of terrestrial connection between island archipelagos of Southeast Asia during the Mid-Pleistocene paleoclimate fluctuations. Our biogeographical analysis also supports the recent introduction of P. leucomystax to the Philippines and Ryukyus, as previously suggested.
The data provided is related to the article "Phylogenetic analyses of gazelles reveal repeated transitions of key ecological traits and provide novel insights into the origin of the genus Gazella". The data is based on 48 tissue samples of all nine extant species of the genus Gazella, namely Gazella gazella, Gazella arabica, Gazella bennettii, Gazella cuvieri, Gazella dorcas, Gazella leptoceros, Gazella marica, Gazella spekei, and Gazella subgutturosa and four related taxa (Saiga tatarica, Antidorcas marsupialis, Antilope cervicapra and Eudorcas rufifrons). It comprises alignments of sequences of a cytochrome b data set and of six nuclear intron markers. For the latter new primers were designed based on cattle and sheep genomes. Based on these alignments phylogenetic trees were inferred using Bayesian Inference and Maximum Likelihood methods. Furthermore, ancestral character states (inferred with BayesTraits 1.0) and ancestral ranges based on a Dispersal-Extinction-Cladogenesis model were estimated and results׳ files were stored within this article.
Osteosarcomas are aggressive bone tumours with a high degree of genetic heterogeneity, which has historically complicated driver gene discovery. Here we sequence exomes of 31 tumours and decipher their evolutionary landscape by inferring clonality of the individual mutation events. Exome findings are interpreted in the context of mutation and SNP array data from a replication set of 92 tumours. We identify 14 genes as the main drivers, of which some were formerly unknown in the context of osteosarcoma. None of the drivers is clearly responsible for the majority of tumours and even TP53 mutations are frequently mapped into subclones. However, >80% of osteosarcomas exhibit a specific combination of single-base substitutions, LOH, or large-scale genome instability signatures characteristic of BRCA1/2-deficient tumours. Our findings imply that multiple oncogenic pathways drive chromosomal instability during osteosarcoma evolution and result in the acquisition of BRCA-like traits, which could be therapeutically exploited.
Although immune checkpoint and targeted therapies offer remarkable benefits for lung cancer treatment, some patients do not qualify for these regimens or do not exhibit consistent benefit. Provided that lung cancer appears to be driven by transforming growth factor beta signaling, we investigated the single drug potency of Pirfenidone, an approved drug for the treatment of lung fibrosis. Five human lung cancer cell lines and one murine line were investigated for transforming growth factor beta inhibition via Pirfenidone by using flow cytometry, In-Cell western analysis, proliferation assays as well as comprehensive analyses of the transcriptome with subsequent bioinformatics analysis. Overall, Pirfenidone induced cell cycle arrest, down-regulated SMAD expression and reduced proliferation in lung cancer. Furthermore, cell stress pathways and pro-apoptotic signaling may be mediated by reduced expression of Survivin. A murine subcutaneous model was used to assess the in vivo drug efficacy of Pirfenidone and showed reduced tumor growth and increased infiltration of T cells and NK cells. This data warrant further clinical evaluation of Pirfenidone with advanced non-small cell lung cancer. The observed in vitro and in vivo effects point to a substantial benefit for using Pirfenidone to reactivate the local immune response and possible application in conjunction with current immunotherapies.
Biotic interchange after the connection of previously independently evolving floras and faunas is thought to be one of the key factors that shaped global biodiversity as we see it today. However, it was not known how biotic interchange develops over longer time periods of several million years following the secondary contact of different biotas. Here we present a novel method to investigate the temporal dynamics of biotic interchange based on a phylogeographical meta-analysis by calculating the maximal number of observed dispersal events per million years given the temporal uncertainty of the underlying time-calibrated phylogenies. We show that biotic influx from mainland Asia onto the Indian subcontinent after Eocene continental collision was not a uniform process, but was subject to periods of acceleration, stagnancy and decrease. We discuss potential palaeoenvironmental causes for this fluctuation.
Heat stress transcription factors (HSFs) regulate transcriptional response to a large number of environmental influences, such as temperature fluctuations and chemical compound applications. Plant HSFs represent a large and diverse gene family. The HSF members vary substantially both in gene expression patterns and molecular functions. HEATSTER is a web resource for mining, annotating, and analyzing members of the different classes of HSFs in plants. A web-interface allows the identification and class assignment of HSFs, intuitive searches in the database and visualization of conserved motifs, and domains to classify novel HSFs.
This article presents a multiscale approach for detecting and monitoring soil erosion phenomena (i.e. gully erosion) in the agro-industrial area around the city of Taroudannt, Souss basin, Morocco. The study area is characterized as semi-arid with an annual average precipitation of 200 mm. Water scarcity, high population dynamics and changing land use towards huge areas of irrigation farming present numerous threats to sustainability. The agro-industry produces citrus fruits and vegetables in monocropping, mainly for the European market. Badland areas strongly affected by gully erosion border the agricultural areas as well as residential areas. To counteract the significant loss of land, land-leveling measures are attempted to create space for plantations and greenhouses. In order to develop sustainable approaches to limit gully growth the detection and monitoring of gully systems is fundamental. Specific gully sites are monitored with unmanned aerial vehicle (UAV) taking small-format aerial photographs (SFAP). This enables extremely high-resolution analysis (SFAP resolution: 2-10 cm) of the actual size of the gully channels as well as a detailed continued surveillance of their growth. Transferring the methodology on a larger scale using Quickbird satellite data (resolution: 60 cm) leads to the possibility of a large-scale analysis of the whole area around the city of Taroudannt (Area extent: ca. 350 km²). The results will then reveal possible relationships of gully growth and agro-industrial management and may even illustrate further interdependencies. The main objective is the identification of areas with high gully-erosion risk due to non-sustainable land use and the development of mitigation strategies for the study area.
Previous studies detected an influence of urban characteristics on song traits in passerine birds, that is, song adjustments to ambient noise in urban areas. Several studies already described the effect of weather conditions on the behavior of birds, but not the effect on song traits. We investigate, if song trait variability changes along a continuous urbanity gradient in Frankfurt am Main, Germany. We examined, for the first time on a larger scale, the influence of weather on song parameters. We made song recordings of three common passerine species: the blue and great tit (Cyanistes caeruleus (Linnaeus, 1758) and Parus major Linnaeus, 1758) and the European blackbird (Turdus merula Linnaeus, 1758). We measured different song traits and performed statistical analyses and modeling on a variety of variables—among them urbanity and weather parameters. Remarkably, we found only few cases of a significant influence of urbanity parameters on song traits. The influence of weather parameters (air pressure, atmospheric humidity, air and soil temperatures) on song traits was highly significant. Birds in Frankfurt face high noise pollution and might show different adaptations to high noise levels. The song trait variability of the investigated species is affected more by weather conditions than by urban characteristics in Frankfurt. However, the three species react differently to specific weather parameters. Smaller species seem to be more affected by weather than larger species.
This article presents an environmental remote sensing application using a UAV that is specifically aimed at reducing the data gap between field scale and satellite scale in soil erosion monitoring in Morocco. A fixed-wing aircraft type Sirius I (MAVinci, Germany) equipped with a digital system camera (Panasonic) is employed. UAV surveys are conducted over different study sites with varying extents and flying heights in order to provide both very high resolution site-specific data and lower-resolution overviews, thus fully exploiting the large potential of the chosen UAV for multi-scale mapping purposes. Depending on the scale and area coverage, two different approaches for georeferencing are used, based on high-precision GCPs or the UAV’s log file with exterior orientation values respectively. The photogrammetric image processing enables the creation of Digital Terrain Models (DTMs) and ortho-image mosaics with very high resolution on a sub-decimetre level. The created data products were used for quantifying gully and badland erosion in 2D and 3D as well as for the analysis of the surrounding areas and landscape development for larger extents.
Unique features of a global human ectoparasite identified through sequencing of the bed bug genome
(2016)
The bed bug, Cimex lectularius, has re-established itself as a ubiquitous human ectoparasite throughout much of the world during the past two decades. This global resurgence is likely linked to increased international travel and commerce in addition to widespread insecticide resistance. Analyses of the C. lectularius sequenced genome (650 Mb) and 14,220 predicted protein-coding genes provide a comprehensive representation of genes that are linked to traumatic insemination, a reduced chemosensory repertoire of genes related to obligate hematophagy, host–symbiont interactions, and several mechanisms of insecticide resistance. In addition, we document the presence of multiple putative lateral gene transfer events. Genome sequencing and annotation establish a solid foundation for future research on mechanisms of insecticide resistance, human–bed bug and symbiont–bed bug associations, and unique features of bed bug biology that contribute to the unprecedented success of C. lectularius as a human ectoparasite.
The novel coronavirus SARS-CoV-2 is the causative agent of the acute respiratory disease COVID-19, which has become a global concern due to its rapid spread. Meanwhile, increased demand for testing has led to a shortage of reagents and supplies and compromised the performance of diagnostic laboratories in many countries. Both the World Health Organization (WHO) and the Center for Disease Control and Prevention (CDC) recommend multi-step RT-PCR assays using multiple primer and probe pairs, which might complicate the interpretation of the test results, especially for borderline cases. In this study, we describe an alternative RT-PCR approach for the detection of SARS-CoV-2 RNA that can be used for the probe-based detection of clinical isolates in diagnostics as well as in research labs using a low-cost SYBR green method. For the evaluation, we used samples from patients with confirmed SARS-CoV-2 infections and performed RT-PCR assays along with successive dilutions of RNA standards to determine the limit of detection. We identified an M-gene binding primer and probe pair highly suitable for the quantitative detection of SARS-CoV-2 RNA for diagnostic and research purposes.
Incorporation of doxorubicin in different polymer nanoparticles and their anticancer activity
(2019)
Background: Nanoparticles are under investigation as carrier systems for anticancer drugs. The expression of efflux transporters such as the ATP-binding cassette (ABC) transporter ABCB1 is an important resistance mechanism in therapy-refractory cancer cells. Drug encapsulation into nanoparticles has been shown to bypass efflux-mediated drug resistance, but there are also conflicting results. To investigate whether easy-to-prepare nanoparticles made of well-tolerated polymers may circumvent transporter-mediated drug efflux, we prepared poly(lactic-co-glycolic acid) (PLGA), polylactic acid (PLA), and PEGylated PLGA (PLGA-PEG) nanoparticles loaded with the ABCB1 substrate doxorubicin by solvent displacement and emulsion diffusion approaches and assessed their anticancer efficiency in neuroblastoma cells, including ABCB1-expressing cell lines, in comparison to doxorubicin solution.
Results: The resulting nanoparticles covered a size range between 73 and 246 nm. PLGA-PEG nanoparticle preparation by solvent displacement led to the smallest nanoparticles. In PLGA nanoparticles, the drug load could be optimised using solvent displacement at pH 7 reaching 53 µg doxorubicin/mg nanoparticle. These PLGA nanoparticles displayed sustained doxorubicin release kinetics compared to the more burst-like kinetics of the other preparations. In neuroblastoma cells, doxorubicin-loaded PLGA-PEG nanoparticles (presumably due to their small size) and PLGA nanoparticles prepared by solvent displacement at pH 7 (presumably due to their high drug load and superior drug release kinetics) exerted the strongest anticancer effects. However, nanoparticle-encapsulated doxorubicin did not display increased efficacy in ABCB1-expressing cells relative to doxorubicin solution.
Conclusion: Doxorubicin-loaded nanoparticles made by different methods from different materials displayed substantial discrepancies in their anticancer activity at the cellular level. Optimised preparation methods resulted in PLGA nanoparticles characterised by increased drug load, controlled drug release, and high anticancer efficacy. The design of drug-loaded nanoparticles with optimised anticancer activity at the cellular level is an important step in the development of improved nanoparticle preparations for anticancer therapy. Further research is required to understand under which circumstances nanoparticles can be used to overcome efflux-mediated resistance in cancer cells.
Incorporation of doxorubicin in different polymer nanoparticles and their anti-cancer activity
(2018)
Nanoparticles are under investigation as carrier systems for anti-cancer drugs. They have been shown to accumulate in cancer tissues through the enhanced permeability and retention (EPR) effect, to reduce toxicity to non-target tissues, and to protect drugs from preliminary inactivation. However, nanoparticle preparations are not commonly compared for their anti-cancer effects at the cellular level. Here, we prepared doxorubicin-loaded nanoparticles based on poly(lactic-co-glycolic acid) (PLGA), polylactic acid (PLA), and PEGylated PLGA (PLGA-PEG) by solvent displacement and emulsion diffusion approaches. The resulting nanoparticles covered a size range between 73 and 246 nm. PLGA-PEG nanoparticle preparation by solvent displacement resulted in the smallest nanoparticles. In PLGA nanoparticles, the drug load could be optimised using solvent displacement at pH7 reaching 53 µg doxorubicin/mg nanoparticle. In addition, these PLGA nanoparticles displayed sustained doxorubicin release kinetics compared to the more burst-like kinetics of the other preparations. In neuroblastoma cells, doxorubicin-loaded PLGA-PEG nanoparticles (presumably due to their small size) and PLGA nanoparticles prepared by solvent displacement at pH7 (presumably due to their high drug load and superior drug release kinetics) exerted the strongest anti-cancer effects. In conclusion, doxorubicin-loaded nanoparticles made by different methods from different materials displayed substantial discrepancies in their anti-cancer activity at the cellular level. Optimised preparation methods resulted in PLGA nanoparticles characterised by increased drug load, controlled drug release, and high anti-cancer efficacy. The design of drug-loaded nanoparticles with optimised anti-cancer activity at the cellular level is an important step in the development of improved nanoparticle preparations for anti-cancer therapy.
Mutations of the isocitrate dehydrogenase-1 (IDH1) and IDH2 genes are among the most frequent alterations in acute myeloid leukemia (AML) and can be found in ∼20% of patients at diagnosis. Among 4930 patients (median age, 56 years; interquartile range, 45-66) with newly diagnosed, intensively treated AML, we identified IDH1 mutations in 423 (8.6%) and IDH2 mutations in 575 (11.7%). Overall, there were no differences in response rates or survival for patients with mutations in IDH1 or IDH2 compared with patients without mutated IDH1/2. However, distinct clinical and comutational phenotypes of the most common subtypes of IDH1/2 mutations could be associated with differences in outcome. IDH1-R132C was associated with increased age, lower white blood cell (WBC) count, less frequent comutation of NPM1 and FLT3 internal tandem mutation (ITD) as well as with lower rate of complete remission and a trend toward reduced overall survival (OS) compared with other IDH1 mutation variants and wild-type (WT) IDH1/2. In our analysis, IDH2-R172K was associated with significantly lower WBC count, more karyotype abnormalities, and less frequent comutations of NPM1 and/or FLT3-ITD. Among patients within the European LeukemiaNet 2017 intermediate- and adverse-risk groups, relapse-free survival and OS were significantly better for those with IDH2-R172K compared with WT IDH, providing evidence that AML with IDH2-R172K could be a distinct entity with a specific comutation pattern and favorable outcome. In summary, the presented data from a large cohort of patients with IDH1/2 mutated AML indicate novel and clinically relevant findings for the most common IDH mutation subtypes.
In the current dismal situation of the COVID-19 pandemic, effective management of patients with pneumonia and acute respiratory distress syndrome is of vital importance. Due to the current lack of effective pharmacological concepts, this situation has caused interest in (re)considering historical reports on the treatment of patients with low-dose radiation therapy for pneumonia. Although these historical reports are of low-level evidence per se, hampering recommendations for decision-making in the clinical setting, they indicate effectiveness in the dose range between 0.3 and 1 Gy, similar to more recent dose concepts in the treatment of acute and chronic inflammatory/degenerative benign diseases with, e.g., a single dose per fraction of 0.5 Gy. This concise review aims to critically review the evidence for low-dose radiation treatment of COVID-19 pneumopathy and discuss whether it is worth investigating in the present clinical situation.
Background: The invasive eel parasite Anguillicoloides crassus (syn. Anguillicola crassus) is considered one of the major causes for the decline of the European eel (Anguilla anguilla) panmictic population. It impairs the swim bladder function and reduces swimming performance of its host. The life cycle of this parasite involves different intermediate and paratenic hosts. Despite an efficient immune system of the paratenic fish hosts acting against infections with A. crassus, levels of parasitized eels remain high in European river systems. Recently, the round goby Neogobius melanostomus (Gobiidae) has become dominant in many rivers in Europe and is still spreading at a rapid pace. This highly invasive species might potentially act as an important, so far neglected paratenic fish host for A. crassus.
Methods: Based on own observations and earlier single sightings of A. crassus in N. melanostomus, 60 fresh individuals of N. melanostomus were caught in the Rhine River and examined to assess the infection levels with metazoan parasites, especially A. crassus. Glycerin preparations were used for parasite identification.
Results: The parasite most frequently found in N. melanostomus was the acanthocephalan Pomphorhynchus sp. (subadult stage) which occurred mainly encysted in the mesenteries and liver. Every third gobiid (P = 31.7%) was infected by A. crassus larvae (L3) which exclusively occurred inside the acanthocephalan cysts. No intact or degenerated larvae of A. crassus were detected elsewhere in the goby, neither in the body cavity and mesenteries nor in other organs. Affected cysts contained the acanthocephalan larvae and 1-12 (mI =3) living A. crassus larvae. Additionally, encysted larvae of the nematode Raphidascaris acus were detected in the gobies, but only in the body cavity and not inside the acanthocephalan cysts.
Conclusions: Based on our observations, we suggest that A. crassus might actively bypass the immune response of N. melanostomus by invading the cysts of acanthocephalan parasites of the genus Pomphorhynchus using them as "Trojan horses". Providing that eels prey on the highly abundant round goby and that the latter transfers viable infective larvae of A. crassus, the new paratenic host might have a strong impact on the epidemiology of A. crassus.
We report here on recent collections of freshwater crabs from Antsiranana Province, northern Madagascar. The specimens belong to three species, one of which is new to science and is described here. This raises the number of species of freshwater crabs found in Madagascar to 17. All are endemic to the island and all belong to the Afrotropical family Potamonautidae Bott, 1970. The new species, Foza manonae sp. nov., is compared to the other species in this genus, and an updated key is provided. It is distinguished from the other three congeners by characters of the male first gonopod, sternum, carapace, and cheliped. The conservation status of the Malagasy freshwater crab fauna is summarized and discussed in light of the new material reported on here belonging to two other species, Madagapotamon humberti Bott, 1965 and Foza ambohitra Cumberlidge & Meyer, 2009.
The acidification of the oceans could potentially alter marine plankton communities with consequences for ecosystem functioning. While several studies have investigated effects of ocean acidification on communities using traditional methods, few have used genetic analyses. Here, we use community barcoding to assess the impact of ocean acidification on the composition of a coastal plankton community in a large scale, in situ, long-term mesocosm experiment. High-throughput sequencing resulted in the identification of a wide range of planktonic taxa (Alveolata, Cryptophyta, Haptophyceae, Fungi, Metazoa, Hydrozoa, Rhizaria, Straminipila, Chlorophyta). Analyses based on predicted operational taxonomical units as well as taxonomical compositions revealed no differences between communities in high CO2 mesocosms (~ 760 μatm) and those exposed to present-day CO2 conditions. Observed shifts in the planktonic community composition were mainly related to seasonal changes in temperature and nutrients. Furthermore, based on our investigations, the elevated CO2 did not affect the intraspecific diversity of the most common mesozooplankter, the calanoid copepod Pseudocalanus acuspes. Nevertheless, accompanying studies found temporary effects attributed to a raise in CO2. Differences in taxa composition between the CO2 treatments could, however, only be observed in a specific period of the experiment. Based on our genetic investigations, no compositional long-term shifts of the plankton communities exposed to elevated CO2 conditions were observed. Thus, we conclude that the compositions of planktonic communities, especially those in coastal areas, remain rather unaffected by increased CO2.
This guideline of the German Dermatology Society primarily focuses on the diagnosis and treatment of cutaneous manifestations of Lyme borreliosis. It has received consensus from 22 German medical societies and 2 German patient organisations. It is the first part of an AWMF (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e.V.) interdisciplinary guideline: "Lyme Borreliosis – Diagnosis and Treatment, development stage S3".
The guideline is directed at physicians in private practices and clinics who treat Lyme borreliosis. Objectives of this guideline are recommendations for confirming a clinical diagnosis, recommendations for a stage-related laboratory diagnosis (serological detection of IgM and IgG Borrelia antibodies using the 2-tiered ELISA/immunoblot process, sensible use of molecular diagnostic and culture procedures) and recommendations for the treatment of the localised, early-stage infection (erythema migrans, erythema chronicum migrans, and borrelial lymphocytoma), the disseminated early-stage infection (multiple erythemata migrantia, flu-like symptoms) and treatment of the late-stage infection (acrodermatitis chronica atrophicans with and without neurological manifestations). In addition, an information sheet for patients containing recommendations for the prevention of Lyme borreliosis is attached to the guideline.
Background: In many species males face a higher predation risk than females because males display elaborate traits that evolved under sexual selection, which may attract not only females but also predators. Females are, therefore, predicted to avoid such conspicuous males under predation risk. The present study was designed to investigate predator-induced changes of female mating preferences in Atlantic mollies (Poecilia mexicana). Males of this species show a pronounced polymorphism in body size and coloration, and females prefer large, colorful males in the absence of predators. Results: In dichotomous choice tests predator-naïve (lab-reared) females altered their initial preference for larger males in the presence of the cichlid Cichlasoma salvini, a natural predator of P. mexicana, and preferred small males instead. This effect was considerably weaker when females were confronted visually with the non-piscivorous cichlid Vieja bifasciata or the introduced non-piscivorous Nile tilapia (Oreochromis niloticus). In contrast, predator experienced (wild-caught) females did not respond to the same extent to the presence of a predator, most likely due to a learned ability to evaluate their predators' motivation to prey. Conclusions: Our study highlights that (a) predatory fish can have a profound influence on the expression of mating preferences of their prey (thus potentially affecting the strength of sexual selection), and females may alter their mate choice behavior strategically to reduce their own exposure to predators. (b) Prey species can evolve visual predator recognition mechanisms and alter their mate choice only when a natural predator is present. (c) Finally, experiential effects can play an important role, and prey species may learn to evaluate the motivational state of their predators. Keywords: Sexual selection; female choice; non-independent mate choice; predator recognition; Poecilia mexicana
The Cueva del Azufre in Tabasco, Mexico, is a nutrient-rich cave and its inhabitants need to cope with high levels of dissolved hydrogen sulfide and extreme hypoxia. One of the successful colonizers of this cave is the poeciliid fish Poecilia mexicana, which has received considerable attention as a model organism to examine evolutionary adaptations to extreme environmental conditions. Nonetheless, basic ecological data on the endemic cave molly population are still missing; here we aim to provide data on population densities, size class compositions and use of different microhabitats. We found high overall densities in the cave and highest densities at the middle part of the cave with more than 200 individuals per square meter. These sites have lower H2S concentrations compared to the inner parts where most large sulfide sources are located, but they are annually exposed to a religious harvesting ceremony of local Zoque people called La Pesca. We found a marked shift in size/age compositions towards an overabundance of smaller, juvenile fish at those sites. We discuss these findings in relation to several environmental gradients within the cave (i.e., differences in toxicity and lighting conditions), but we also tentatively argue that the annual fish harvest during a religious ceremony (La Pesca) locally diminishes competition (and possibly, cannibalism by large adults), which is followed by a phase of overcompensation of fish densities.
Psoriasis vulgaris is a common and chronic inflammatory skin disease which has the potential to significantly reduce the quality of life in severely affected patients. The incidence of psoriasis in Western industrialized countries ranges from 1.5 to 2%. Despite the large variety of treatment options available, patient surveys have revealed insufficient satisfaction with the efficacy of available treatments and a high rate of medication non-compliance. To optimize the treatment of psoriasis in Germany, the Deutsche Dermatologische Gesellschaft and the Berufsverband Deutscher Dermatologen (BVDD) have initiated a project to develop evidence-based guidelines for the management of psoriasis. The guidelines focus on induction therapy in cases of mild, moderate, and severe plaque-type psoriasis in adults. The short version of the guidelines reported here consist of a series of therapeutic recommendations that are based on a systematic literature search and subsequent discussion with experts in the field; they have been approved by a team of dermatology experts. In addition to the therapeutic recommendations provided in this short version, the full version of the guidelines includes information on contraindications, adverse events, drug interactions, practicality, and costs as well as detailed information on how best to apply the treatments described (for full version, please see Nast et al., JDDG, Suppl 2:S1–S126, 2006; or http://www.psoriasis-leitlinie.de).
Resilience has been defined as the maintenance or quick recovery of mental health during and after times of adversity. How to operationalize resilience and to determine the factors and processes that lead to good long-term mental health outcomes in stressor-exposed individuals is a matter of ongoing debate and of critical importance for the advancement of the field. One of the biggest challenges for implementing an outcome-based definition of resilience in longitudinal observational study designs lies in the fact that real-life adversity is usually unpredictable and that its substantial qualitative as well as temporal variability between subjects often precludes defining circumscribed time windows of inter-individually comparable stressor exposure relative to which the maintenance or recovery of mental health can be determined. To address this pertinent issue, we propose to frequently and regularly monitor stressor exposure (E) and mental health problems (P) throughout a study's observation period [Frequent Stressor and Mental Health Monitoring (FRESHMO)-paradigm]. On this basis, a subject's deviation at any single monitoring time point from the study sample's normative E–P relationship (the regression residual) can be used to calculate that subject's current mental health reactivity to stressor exposure (“stressor reactivity,” SR). The SR score takes into account the individual extent of experienced adversity and is comparable between and within subjects. Individual SR time courses across monitoring time points reflect intra-individual temporal variability in SR, where periods of under-reactivity (negative SR score) are associated with accumulation of fewer mental health problems than is normal for the sample. If FRESHMO is accompanied by regular measurement of potential resilience factors, temporal changes in resilience factors can be used to predict SR time courses. An increase in a resilience factor measurement explaining a lagged decrease in SR can then be considered to index a process of adaptation to stressor exposure that promotes a resilient outcome (an allostatic resilience process). This design principle allows resilience research to move beyond merely determining baseline predictors of resilience outcomes, which cannot inform about how individuals successfully adjust and adapt when confronted with adversity. Hence, FRESHMO plus regular resilience factor monitoring incorporates a dynamic-systems perspective into resilience research.
Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental disorder. Genetic loci have not yet been identified by genome-wide association studies. Rare copy number variations (CNVs), such as chromosomal deletions or duplications, have been implicated in ADHD and other neurodevelopmental disorders. To identify rare (frequency ≤1%) CNVs that increase the risk of ADHD, we performed a whole-genome CNV analysis based on 489 young ADHD patients and 1285 adult population-based controls and identified one significantly associated CNV region. In tests for a global burden of large (>500 kb) rare CNVs, we observed a nonsignificant (P=0.271) 1.126-fold enriched rate of subjects carrying at least one such CNV in the group of ADHD cases. Locus-specific tests of association were used to assess if there were more rare CNVs in cases compared with controls. Detected CNVs, which were significantly enriched in the ADHD group, were validated by quantitative (q)PCR. Findings were replicated in an independent sample of 386 young patients with ADHD and 781 young population-based healthy controls. We identified rare CNVs within the parkinson protein 2 gene (PARK2) with a significantly higher prevalence in ADHD patients than in controls (P=2.8 × 10(-4) after empirical correction for genome-wide testing). In total, the PARK2 locus (chr 6: 162 659 756-162 767 019) harboured three deletions and nine duplications in the ADHD patients and two deletions and two duplications in the controls. By qPCR analysis, we validated 11 of the 12 CNVs in ADHD patients (P=1.2 × 10(-3) after empirical correction for genome-wide testing). In the replication sample, CNVs at the PARK2 locus were found in four additional ADHD patients and one additional control (P=4.3 × 10(-2)). Our results suggest that copy number variants at the PARK2 locus contribute to the genetic susceptibility of ADHD. Mutations and CNVs in PARK2 are known to be associated with Parkinson disease.
TRIANNI mice carry an entire set of human immunoglobulin V region gene segments and are a powerful tool to rapidly isolate human monoclonal antibodies. After immunizing these mice with DNA encoding the spike protein of SARS-CoV-2 and boosting with spike protein, we identified 29 hybridoma antibodies that reacted with the SARS-CoV-2 spike protein. Nine antibodies neutralize SARS-CoV-2 infection at IC50 values in the subnanomolar range. ELISA-binding studies and DNA sequence analyses revealed one cluster of three clonally related neutralizing antibodies that target the receptor-binding domain and compete with the cellular receptor hACE2. A second cluster of six clonally related neutralizing antibodies bind to the N-terminal domain of the spike protein without competing with the binding of hACE2 or cluster 1 antibodies. SARS-CoV-2 mutants selected for resistance to an antibody from one cluster are still neutralized by an antibody from the other cluster. Antibodies from both clusters markedly reduced viral spread in mice transgenic for human ACE2 and protected the animals from SARS-CoV-2-induced weight loss. The two clusters of potent noncompeting SARS-CoV-2 neutralizing antibodies provide potential candidates for therapy and prophylaxis of COVID-19. The study further supports transgenic animals with a human immunoglobulin gene repertoire as a powerful platform in pandemic preparedness initiatives.
Background: For prostate cancer treatment, treatment options with minimal side effects are desired. External beam radiation therapy (EBRT) is non-invasive, standard of care and delivered in either conventional fractionation over 8 weeks or with moderate hypo-fractionation over about 5 weeks. Recent advances in radiotherapy technology have made extreme hypo-fractionated stereotactic body radiation therapy (SBRT) of prostate cancer feasible, which has not yet been introduced as a standard treatment method in Germany. Initial results from other countries are promising, but long-term results are not yet available. The aim of this study is to investigate feasibility and effectiveness of SBRT for prostate cancer in Germany.
Methods/design: This German bi-center single group trial (HYPOSTAT) is designed to evaluate feasibility and effectiveness, as measured by toxicity and PSA-response, respectively, of an extreme hypo-fractionated SBRT regimen with five fractions of 7 Gy in treatment of localized low and intermediate risk prostate cancer. The target volume includes the prostate with or without the base of seminal vesicles depending on risk stratification and uncertainty margins that are kept at 3–5 mm. SBRT treatment is delivered with the robotic CyberKnife system, which was recently introduced in Germany. Acute and late toxicity after one year will be evaluated according to Common Terminology Criteria for Adverse Events (CTCAE v. 4.0), Radiation Therapy Oncology Group (RTOG) and International Prostate Symptom Score (IPSS) Scores. The quality of life will be assessed before and after treatment with the EORTC QLQ C30 questionnaire. Hypothesizing that the proportion of patients with grade 2 side effects or higher is less or equal than 2.8%, thus markedly lower than the standard EBRT percentage (17.5%), the recruitment target is 85 patients.
Discussion: The HYPOSTAT trial aims at demonstrating short term feasibility of extreme hypo-fractioned SBRT for the treatment of prostate cancer and might be used as the pilot study for a multi-center multi-platform or for randomized-controlled trials comparing conventional radiotherapy with SBRT for localized prostate cancer in the future. The study concept of patient enrollment, follow up and evaluation by multiple public university clinics and actual patient treatment in dedicated private radiosurgery practices with high-tech radiation equipment is unique for clinical trials.
Study status: The study is ongoing and currently recruiting patients.
Trial registration: Registration number: NCT02635256 (clinicaltrials.gov). Registered 8 December 2015
The nucleosynthesis of elements beyond iron is dominated by neutron captures in the s and r processes. However, 32 stable, proton-rich isotopes cannot be formed during those processes, because they are shielded from the s-process flow and r-process β-decay chains. These nuclei are attributed to the p and rp process.
For all those processes, current research in nuclear astrophysics addresses the need for more precise reaction data involving radioactive isotopes. Depending on the particular reaction, direct or inverse kinematics, forward or time-reversed direction are investigated to determine or at least to constrain the desired reaction cross sections.
The Facility for Antiproton and Ion Research (FAIR) will offer unique, unprecedented opportunities to investigate many of the important reactions. The high yield of radioactive isotopes, even far away from the valley of stability, allows the investigation of isotopes involved in processes as exotic as the r or rp processes.
Transverse momentum spectra of π±, K± and p(p¯) up to pT = 20 GeV/c at mid-rapidity in pp and Pb-Pb collisions at sNN−−−√= 2.76 TeV have been measured using the ALICE detector at the Large Hadron Collider. The proton-to-pion and the kaon-to-pion ratios both show a distinct peak at pT≈3GeV/c in central Pb-Pb collisions. Below the peak, pT < 3 GeV/c, both ratios are in good agreement with hydrodynamical calculations, suggesting that the peak itself is dominantly the result of radial flow rather than anomalous hadronization processes. For pT > 10 GeV/c particle ratios in pp and Pb-Pb collisions are in agreement and the nuclear modification factors for π±, K± and p(p¯) indicate that, within the systematic and statistical uncertainties, the suppression is the same. This suggests that the chemical composition of leading particles from jets in the medium is similar to that of vacuum jets.