julilili42/papers huggingface dataset:
A Terminal Yttrium Phosphinidene
2023-08-02

Terminal, nondirectional ionic "multiple" bond interactions between group 15 elements and rare-earth metals (Ln) have remained a challenging target until present. Although reports on terminal imide species have accumulated in the meantime, examples of terminal congeners with the higher homologue phosphorus are yet elusive. Herein, we present the synthesis of the first terminal yttrium organophosphinidene complex, Tp<sup><i>t</i>Bu,Me</sup>Y(═PC<sub>6</sub>H<sub>3</sub><i>i</i>Pr<sub>2</sub>-2,6)(DMAP)<sub>2</sub>, according to a double-deprotonation sequence previously established for organoimides of the smaller rare-earth metals. Subsequent deprotonation of the primary phosphane H<sub>2</sub>PC<sub>6</sub>H<sub>3</sub><i>i</i>Pr<sub>2</sub>-2,6 (H<sub>2</sub>PAr<sup><i>i</i>Pr</sup>) with discrete dimethyl compound Tp<sup><i>t</i>Bu,Me</sup>YMe<sub>2</sub> in the presence of DMAP under simultaneous methane elimination generated a terminal multiply bonded phosphorus. The primary phosphide intermediates Tp<sup><i>t</i>Bu,Me</sup>YMe(HPAr<sup><i>i</i>Pr</sup>) and Tp<sup><i>t</i>Bu,Me</sup>YMe(HNPAr<sup><i>i</i>Pr</sup>)(DMAP) are isolable species and were also obtained and fully characterized for holmium and dysprosium. The Lewis acid-stabilized yttrium phosphinidene Tp<sup><i>t</i>Bu,Me</sup>Y[(μ<sub>2</sub>-PAr<sup><i>i</i>Pr</sup>)(μ<sub>2</sub>-Me)AlMe<sub>2</sub>] was obtained by treatment of H<sub>2</sub>PAr<sup><i>i</i>Pr</sup> with Tp<sup><i>t</i>Bu,Me</sup>YMe(AlMe<sub>4</sub>) but could not be converted into a terminal phosphinidene via cleavage of trimethylaluminum. The corresponding reaction of H<sub>2</sub>PAr<sup><i>i</i>Pr</sup> with Tp<sup><i>t</i>Bu,Me</sup>YMe(GaMe<sub>4</sub>) led to adduct [GaMe<sub>3</sub>(PH<sub>2</sub>Ar<sup><i>i</i>Pr</sup>)] rather than to the formation of a yttrium phosphinidene. The yttrium-phosphorus interaction in the obtained organophosphide and phosphinidene complexes was scrutinized by <sup>31</sup>P/<sup>89</sup>Y NMR spectroscopy and DFT calculations, unambiguously supporting the existence of multiple bonding.
Hemizygous variants in protein phosphatase 1 regulatory subunit 3F (PPP1R3F) are associated with a neurodevelopmental disorder characterized by developmental delay, intellectual disability and autistic features
2023-08-02

Abstract Protein phosphatase 1 regulatory subunit 3F (PPP1R3F) is a member of the glycogen targeting subunits (GTSs), which belong to the large group of regulatory subunits of protein phosphatase 1 (PP1), a major eukaryotic serine/threonine protein phosphatase that regulates diverse cellular processes. Here, we describe the identification of hemizygous variants in PPP1R3F associated with a novel X-linked recessive neurodevelopmental disorder in 13 unrelated individuals. This disorder is characterized by developmental delay, mild intellectual disability, neurobehavioral issues such as autism spectrum disorder, seizures and other neurological findings including tone, gait and cerebellar abnormalities. PPP1R3F variants segregated with disease in affected hemizygous males that inherited the variants from their heterozygous carrier mothers. We show that PPP1R3F is predominantly expressed in brain astrocytes and localizes to the endoplasmic reticulum in cells. Glycogen content in PPP1R3F knockout astrocytoma cells appears to be more sensitive to fluxes in extracellular glucose levels than in wild-type cells, suggesting that PPP1R3F functions in maintaining steady brain glycogen levels under changing glucose conditions. We performed functional studies on nine of the identified variants and observed defects in PP1 binding, protein stability, subcellular localization and regulation of glycogen metabolism in most of them. Collectively, the genetic and molecular data indicate that deleterious variants in PPP1R3F are associated with a new X-linked disorder of glycogen metabolism, highlighting the critical role of GTSs in neurological development. This research expands our understanding of neurodevelopmental disorders and the role of PP1 in brain development and proper function.
kcnj13regulates pigment cell shapes in zebrafish and has diverged by cis-regulatory evolution betweenDaniospecies
2023-08-02

ABSTRACT Teleost fish of the genus Danio are excellent models to study the genetic and cellular bases of pigment pattern variation in vertebrates. The two sister species Danio rerio and Danio aesculapii show divergent patterns of horizontal stripes and vertical bars that are partly caused by the divergence of the potassium channel gene kcnj13. Here, we show that kcnj13 is required only in melanophores for interactions with xanthophores and iridophores, which cause location-specific pigment cell shapes and thereby influence colour pattern and contrast in D. rerio. Cis-regulatory rather than protein coding changes underlie kcnj13 divergence between the two Danio species. Our results suggest that homotypic and heterotypic interactions between the pigment cells and their shapes diverged between species by quantitative changes in kcnj13 expression during pigment pattern diversification.
Dickkopf1 induces enteric neurogenesis and gliogenesis in vitro if apoptosis is evaded
2023-08-02

Abstract Neurogenesis in the postnatal enteric nervous system (ENS) is controversially discussed. Yet, deciphering the regenerative potential of the ENS is essential for our understanding and therapy of human enteric neuropathies. Dickkopf1 (DKK1) is a Wnt-antagonist and involved in the homeostasis of various tissues. We hypothesize that DKK1 could function as a negative regulator on the proliferation of ENS-progenitors in the postnatal gut of mice and human infants. Here, we provide evidence that DKK1 is expressed in the murine and human ENS. If applied to ENS-progenitors in vitro, DKK1 leads to an increased proliferation, however, followed by extensive apoptosis. Yet, once we block apoptosis, DKK1-stimulation markedly increases enteric neurogenesis in murine and human ENS-progenitors. Thus, DKK1 is a strong, ambivalent regulator of the ENS-progenitor cell pool in mice and humans. These results are fundamental steps to reshaping our understanding of the homeostasis of the ENS in health and disease.
Influence of colored face masks on judgments of facial attractiveness and gaze patterns
2023-08-02

The study findings indicate that there is an interplay between the gender and age of the participant and the facial stimuli. The color red did have an effect on the perception attractiveness, however not in female faces. The results suggest that masks, especially red ones, might be more beneficial for male faces, which were perceived as less attractive without a mask. However, wearing a mask did not significantly impact already attractive faces. The eye-tracking results revealed that the periorbital region attracted more attention and was fixated on more quickly while wearing a mask, indicating the importance of eyes in social interaction and aesthetic perception.
Autotrophic growth of E. coli is achieved by a small number of genetic changes
2023-08-02

Abstract Synthetic autotrophy is a promising avenue to sustainable bioproduction from CO2. Here, we use iterative laboratory evolution to generate genetically diverse autotrophic strains. We identify that just three mutations are sufficient for E. coli to grow autotrophically, when introduced alongside non-native energy (formate dehydrogenase) and carbon-fixing (Rubisco, phosphoribulokinase, carbonic anhydrase) modules. The mutated genes are involved in glycolysis (pgi), central-carbon regulation (crp), and RNA transcription (rpoB). The pgi mutation reduces the enzyme activity, thereby stabilising the carbon-fixing cycle by capping a major branching flux. The other two mutations increase the ratio of NADH/NAD+ - the cycle’s electron-donor. This study demonstrates the malleability of metabolism and evolution’s capacity to switch trophic modes on laboratory time-scales and could facilitate transforming other heterotrophic organisms into autotrophs.
Oral language comprehension of young adults with low-level reading comprehension
2023-08-02

Significant difficulties in reading comprehension, despite attendance of compulsory schooling, are a worldwide phenomenon. While previous research on adults with low literacy skills focused primarily on their reading ability, less is known about their oral language skills. In this Brief Research Report , we present an investigation of the listening comprehension skills of a selected group of German-speaking young adults, whose reading comprehension is at a primary school level ( n = 32, ages 16 to 19 years). In addition, the relationship between listening comprehension and reading comprehension, beyond word reading skills, was tested. Standardized tests of reading and listening comprehension in the German language were administered. The average performance of the group in the listening comprehension tasks was below the level expected by age and educational level. In addition, when entered into a stepwise regression equation, listening comprehension, but not word reading, explained a significant amount of variance in reading comprehension. This pattern of relationship differs from previous findings in studies of adults struggling to read the opaque English orthography. Whether orthographic transparency explains this discrepancy should be further tested in cross-orthography studies with larger samples of adults with low literacy skills.
Spatial subsetting enables integrative modeling of oral squamous cell carcinoma multiplex imaging data
2023-08-02

The following folders/files are part of this repository: Zip-Archive "OSCC-IMC-Einhaus2023" contains all the data and code necessary reproduce all analysis steps: Folder "UOPCohort": Contains all data and code regarding the OSCC cohort collected at UOP. Folder "Dataframes": All output dataframes produced in the script "Analysis_UOP.Rmd". Folder "Metadata": Existing clinical metadata and output files of the folder "Tumormasks". Folder "Steinbock": Raw data and single-cell segmentation output after Steinbock segmentation. Folder "Tumormasks": All scripts necessary to generate tumormasks, measure celldistances from the tumorborder, and calculate zonal areas. Output files are stored in the folder "Metadata". Script "Analysis_UOP.Rmd": Code for cell phenotyping and feature matrix generation. Folder "STACohort": Contains all data and code regarding the OSCC cohort collected at STA. Folder "Dataframes": All output dataframes produced in the script "Analysis_STA.Rmd". Folder "Metadata": Existing clinical metadata and output files of the folder "Tumormasks". Folder "Steinbock": Raw data and single-cell segmentation output after Steinbock segmentation. Folder "Tumormasks": All scripts necessary to generate tumormasks, measure celldistances from the tumorborder, and calculate zonal areas. Output files are stored in the folder "Metadata". Script "Analysis_STA.Rmd": Code for cell phenotyping and feature matrix generation. Folder "AnalysisMultivariate": Code required to reproduce the multivariate model generated. Input data is pulled from the folder "UOPCohort". Folder "Model": Output data produced by the Jupiter notebook "Model.pynb". Folder "stabl": Contains a modified Python package (STABL). Folder "AnalysisUnivariate": Code required to reproduce the univariate analysis of all features. Input files are pulled from the folders "STACohort" and "UOPCohort". Folder "Visualization": Code required to reproduce figure 1-6 and supplemental figures 1-11. Input files for visualization are pulled from the folders "STACohort" and "UOPCohort". PDF "OSCC-IMC-SupplementalMaterial" contains supplemental tables and figures.
Reactivation strength during cued recall is modulated by graph distance within cognitive maps
2023-08-02

Declarative memory retrieval is thought to involve reinstatement of neuronal activity patterns elicited and encoded during a prior learning episode. Furthermore, it is suggested that two mechanisms operate during reinstatement, dependent on task demands: individual memory items can be reactivated simultaneously as a clustered occurrence or, alternatively, replayed sequentially as temporally separate instances. In the current study, participants learned associations between images that were embedded in a directed graph network and retained this information over a brief 8-minute consolidation period. During a subsequent cued recall session, participants retrieved the learned information while undergoing magnetoencephalographic (MEG) recording. Using a trained stimulus decoder, we found evidence for clustered reactivation of learned material. Reactivation strength of individual items during clustered reactivation decreased as a function of increasing graph distance, an ordering present solely for successful retrieval but not for retrieval failure. In line with previous research, we found evidence that sequential replay was dependent on retrieval performance and was most evident in low performers. The results provide evidence for distinct performance-dependent retrieval mechanisms with graded clustered reactivation emerging as a plausible mechanism to search within abstract cognitive maps.
Dynamics of abdominal symptoms during the start of a new therapy with Elexacaftor/Tezacaftor/Ivacaftor using the novel CFAbd-day2day questionnaire
2023-08-02

Abstract Background Elexacaftor-tezacaftor-ivacaftor (ETI) is a novel highly effective CFTR modulator combination proven to improve lung function and body weight in people with Cystic Fibrosis (pwCF) carrying a F508del mutation. Recently, we revealed significant reductions of abdominal symptoms (AS) in German, British and Irish pwCF after 24-26 weeks of ETI using the CFAbd-Score, the first PROM specifically developed and validated for pwCF following FDA guidelines. Notably, many pwCF reported marked changes in their AS during the first days of the new treatment. To capture these immediate effects, we developed the CFAbd-day2day, a CF-specific GI-diary, following FDA and COSMIN guidelines. Aims To prospectively capture immediate dynamics of AS using the CFAbd-day2day 14 days before and 14-28 days after ETI initiation. In addition, we aim here to provide validation steps of the novel PROM concerning sensitivity to changes. Methods To develop the CFAbd-day2day, focus groups (community voice=pwCF and their proxies and CF specialists from different fields) were repeatedly consulted. Before and under the new ETI therapy pwCF prospectively scored AS on a daily basis with the CFAbd-day2day. Results Altogether, n=45 pwCF attended in 5 CF centers prospectively completed the CFAbd-day2day before (mean±sd: −14±7 days) and after (mean±sd: 28±23 days) ETI initiation. Whereas cumulative scores significantly decreased during the 3-4-week time frame after ETI initiation, compared to the two weeks prior to therapy, many patients who revealed a relatively stable level of AS before ETI reported changes during the first days of treatment with the highly effective CFTR modulators. Items like pain and flatulence increased in up to 21% of patients during the first 14 days of therapy but they improved during days 15-27. Conclusion The CFAbd-day2day, specifically developed and in process of validation to prospectively capture GI symptoms in pwCF, provides new substantial insights into the dynamics of AS in pwCF receiving a new treatment with ETI. The novel tool is also helpful to prospectively monitor patients with specific GI problems. International implementation and further validation steps of the diary are ongoing.
Reads-per-UMI tables across single-cell RNA sequencing protocols
2023-08-02

Data analyzed in Lause, Ziegenhain et al. (2023). Code to obtain these tables from public data sources is available on github. Each row in the table is a UMI-tag detected in a certain cell (column RG) attached to a molecule from a specific gene (column GE) with a certain barcode (column UB). Column N gives the number of times the UMI was detected for that gene and cell. Data sources and protocols are given with the respective file names below. <strong>Johnsson2022_Smartseq3_PE.hd1.txt.gz</strong>: Mouse fibroblasts profiled with <strong>Smart-seq3</strong> paired-end; accession E-MTAB-10148, sample plate2,<br> Paper<br> <br> <strong>Hagemann-Jensen2020_Smartseq3_SE.hd1.txt.gz: </strong>Mouse fibroblasts profiled with <strong>Smart-seq3</strong> single-end; accession E-MTAB-8735, sample Smartseq3.Fibroblasts.smFISH<br> Paper<br> <br> <strong>Hagemann-Jensen2022_Smartseq3xpress.hd1.txt.gz: </strong>HEK293 cells profiled with <strong>Smart-seq3Xpress</strong>; accession E-MTAB-11467.<br> Paper<br> <br> <strong>Ziegenhain2017.hd1.txt.gz: </strong>Mouse embryonic stem cells profiled by <strong>CEL-seq2, Drop-seq, MARS-seq, </strong>and<strong> SCRB-seq</strong>; GEO accession GSE75790<br> Paper
Novel Insight into Microbially Mediated Nitrate-Reducing Fe(II) Oxidation by Acidovorax sp. Strain BoFeN1 Using Dual N–O Isotope Fractionation
2023-08-03

Microbially mediated nitrate reduction coupled with Fe(II) oxidation (NRFO) plays an important role in the Fe/N interactions in pH-neutral anoxic environments. However, the relative contributions of the chemical and microbial processes to NRFO are still unclear. In this study, N-O isotope fractionation during NRFO was investigated. The ratios of O and N isotope enrichment factors (<sup>18</sup>ε:<sup>15</sup>ε)-NO<sub>3</sub><sup>-</sup> indicated that the main nitrate reductase functioning in <i>Acidovorax</i> sp. strain BoFeN1 was membrane-bound dissimilatory nitrate reductase (Nar). N-O isotope fractionation during chemodenitrification [Fe(II) + NO<sub>2</sub><sup>-</sup>], microbial nitrite reduction (cells + NO<sub>2</sub><sup>-</sup>), and the coupled process [cells + NO<sub>2</sub><sup>-</sup> + Fe(II)] was explored. The ratios of (<sup>18</sup>ε:<sup>15</sup>ε)-NO<sub>2</sub><sup>-</sup> were 0.58 ± 0.05 during chemodenitrification and -0.41 ± 0.11 during microbial nitrite reduction, indicating that N-O isotopes can be used to distinguish chemical from biological reactions. The (<sup>18</sup>ε:<sup>15</sup>ε)-NO<sub>2</sub><sup>-</sup> of 0.70 ± 0.05 during the coupled process was close to that obtained for chemodenitrification, indicating that chemodenitrification played a more important role than biological reactions during the coupled process. The results of kinetic modeling showed that the relative contribution of chemodenitrification was 99.3% during the coupled process, which was consistent with that of isotope fractionation. This study provides a better understanding of chemical and biological mechanisms of NRFO using N-O isotopes and kinetic modeling.
Hepatokine‐based identification of fibrotic NASH and improved risk stratification in a multicentre cohort of NAFLD patients
2023-08-03

Abstract Background and Aims The presence of significant liver fibrosis associated with non‐alcoholic steatohepatitis (NASH) is regarded as the major prognostic factor in non‐alcoholic fatty liver disease (NAFLD). Identification of patients at risk for NASH with significant fibrosis is therefore important. Although the established fibrosis score FIB‐4 is suitable to exclude advanced fibrosis, it does not allow the prediction of significant fibrosis in NAFLD patients. We therefore evaluated whether the hepatokine fibroblast growth factor 21 (FGF21), a regulator of glucose and lipid metabolism, might identify ‘at‐risk NASH’ in NAFLD. Methods FGF21 levels were assessed by enzyme‐linked immunosorbent assay in sera from an exploration ( n = 137) and a validation ( n = 88) cohort of biopsy‐proven NAFLD patients with different disease activity and fibrosis stages. In addition, we evaluated whether the use of FGF21 could improve risk stratification in NAFLD patients with low (&lt;1.3) or intermediate (1.3–2.67) FIB‐4. Results FGF21 levels could significantly discriminate between NASH and non‐alcoholic fatty liver (NAFL) patients, even in the absence of diabetes. Moreover, patients with NASH and fibrosis ≥F2 showed significantly higher FGF21 levels compared to NAFLD patients without significant fibrosis. Significantly elevated FGF21 levels could even be detected in NAFLD patients with NASH and significant fibrosis despite low or intermediate FIB‐4. Conclusion Serological FGF21 detection might allow the identification of NAFLD patients at risk and improves patient stratification in combination with FIB‐4.
Protocol for establishing a coculture with fibroblasts and colorectal cancer organoids
2023-08-03

The tumor microenvironment is essential for mediating drug resistance and tumor progression. Here, we present a coculture system, which enables drug testing of colorectal cancer organoids and fibroblasts without additional matrix components such as Matrigel or basement membrane extracts. First, we describe steps to use a readout for high-throughput drug testing using a luminescence-based viability assay. Second, we detail a readout that uses flow cytometry to distinguish toxic effects on either colorectal cancer organoids or fibroblasts.
The rise of bronze in Central Asia: new evidence for the origin of Bronze Age tin and copper from multi-analytical research
2023-08-03

The Bronze Age in Central Asia was dominated by the Andronovo Culture and the Bactria-Margiana Archaeological Complex (BMAC). Both cultural entities produced bronze, however, the extent of bronze production and use varied considerably in space and time across their territories. The introduction and spread of bronze metallurgy in the region is commonly associated with the Andronovo Culture, but comparatively little is known about the copper and tin sources that were exploited to make the bronze. To shed light on this aspect, this paper examines 91 bronze artefacts from the Middle Bronze Age (MBA) and the Late Bronze Age (LBA) recovered from twenty sites of Andronovo and the BMAC through a combined evaluation of chemical and isotopic analyses. Trace element patterns and isotopic compositions of lead, tin, and copper are determined for the objects complemented by tin isotope analysis of Central Asian tin ores. The data shows a clear separation of two source areas in the MBA and LBA I: the BMAC obtained copper from polymetallic (tin-bearing) deposits in Iran (Deh Hosein, Nakhlak/Bagh Gorogh) and possibly Afghanistan, while the Andronovo Culture mainly used copper from the Tian Shan Mountains. With the transition to the LBA II, a change in the material basis can be recognised, in which the BMAC increasingly relied on metal deposits from the Andronovo territory. The most important result in this context is the analytical proof of the coextraction of copper and tin from the copper-tin mine at Mushiston, Tajikistan, and the first direct link of tin in bronze objects with a tin deposit. Mushiston apparently supplied both cultural macro regions with a “natural” bronze, which accounted for about one third of all objects analysed, but there is no indication yet that metal or ores from Mushiston were traded or used at a distance of more than 500 km. Moreover, the artefact data indicates a decline in the exploitation of the mine in the course of the developed LBA, while other copper and tin sources in the Tian Shan and probably the Hindukush were exploited. This testifies to the intensive use of the rich mineral resources of Central Asia and beyond, as well as the intensification of cultural and trade contacts between Andronovo and the BMAC.