bluuebunny/crossref_metadata_2025_split huggingface dataset:
The N-terminus of the
Aspergillus fumigatus
group III hybrid histidine kinase TcsC is essential for its physiological activity and targets the protein to the nucleus
Authors: Vincek Anna , Wolf Anja , Thomas Astrid , Ebel Frank , Schruefer Sebastian 
Published: June 2024

ABSTRACT

Group III hybrid histidine kinases are fungal-specific proteins and part of the multistep phosphorelay, representing the initial part of the high osmolarity glycerol (HOG) pathway. TcsC, the corresponding kinase in
Aspergillus fumigatus,
was expected to be a cytosolic protein but is targeted to the nucleus. Activation of TcsC by the antifungal fludioxonil has lethal consequences for the fungus. The agent triggers a fast and TcsC-dependent activation of SakA and later on a redistribution of TcsC to the cytoplasm. High osmolarity also activates TcsC, which then exits the nucleus or concentrates in spot-like, intra-nuclear structures. The sequence corresponding to the N-terminal 208 amino acids of TcsC lacks detectable domains. Its loss renders TcsC cytosolic and non-responsive to hyperosmotic stress, but it has no impact on the antifungal activity of fludioxonil. A point mutation in one of the three putative nuclear localization sequences, which are present in the N-terminus, prevents the nuclear localization of TcsC, but not its ability to respond to hyperosmotic stress. Hence, this striking intracellular localization is no prerequisite for the role of TcsC in the adaptive response to hyperosmotic stress, instead, TcsC proteins that are present in the nuclei seem to modulate the cell wall composition of hyphae, which takes place in the absence of stress. The results of the present study underline that the spatiotemporal dynamics of the individual components of the multistep phosphorelay is a crucial feature of this unique signaling hub.

IMPORTANCE

Signaling pathways enable pathogens, such as
Aspergillus fumigatus
, to respond to a changing environment. The TcsC protein is the major sensor of the high osmolarity glycerol (HOG) pathway of
A. fumigatus
and it is also the target of certain antifungals. Insights in its function are therefore relevant for the pathogenicity and new therapeutic treatment options. TcsC was expected to be cytoplasmic, but we detected it in the nucleus and showed that it translocates to the cytoplasm upon activation. We have identified the motif that guides TcsC to the nucleus. An exchange of a single amino acid in this motif prevents a nuclear localization, but this nuclear targeting is no prerequisite for the TcsC-mediated stress response. Loss of the N-terminal 208 amino acids prevents the nuclear localization and renders TcsC unable to respond to hyperosmotic stress demonstrating that this part of the protein is of crucial importance.
Draft genome assembly of
Lactobacillus johnsonii
UMB3423 from a voided urine sample
Authors: Stegman Natalie , Steiling Maria , Jackson Briana , Sedano Cerena , Putonti Catherine 
Published: June 2024

ABSTRACT

While the urogenital microbiota of asymptomatic females is often dominated by species of
Lactobacillus
,
Lactobacillus johnsonii
is not a common member. It is more frequently found in the gastrointestinal tract. Here, we present the draft genome sequence of
L. johnsonii
UMB3423, which was isolated from a voided urine sample.
Cleaner anaerobic fermentation and greenhouse gas reduction of crop straw
Authors: Du Zhumei , Nakagawa Andressa , Fang Jiachen , Ridwan Roni , Astuti Wulansih D. , Sarwono Ki A. , Sofyan Ahmad , Widyastuti Yantyati , Cai Yimin 
Published: June 2024

ABSTRACT

Rice anaerobic fermentation is a significant source of greenhouse gas (GHG) emissions, and in order to efficiently utilize crop residue resources to reduce GHG emissions, rice straw anaerobic fermentation was regulated using lactic acid bacteria (LAB) inoculants (FG1 and TH14), grass medium (GM) to culture LAB, and
Acremonim cellulolyticus
(AC). Microbial community, GHG emission, dry matter (DM) loss, and anaerobic fermentation were analyzed using PacBio single-molecule real-time and anaerobic fermentation system. The epiphytic microbial diversity of fresh rice straw was extremely rich and contained certain nutrients and minerals. During ensiling, large amounts of GHG such as carbon dioxide are produced due to plant respiration, enzymatic hydrolysis reactions, and proliferation of aerobic bacteria, resulting in energy and DM loss. Addition of FG1, TH14, and AC alone improved anaerobic fermentation by decreasing pH and ammonia nitrogen content (
P
< 0.05) and increased lactic acid content (
P
< 0.05) when compared to the control, and GM showed the same additive effect as LAB inoculants. Microbial additives formed a co-occurrence microbial network system dominated by LAB, enhanced the biosynthesis of secondary metabolites, diversified the microbial metabolic environment and carbohydrate metabolic pathways, weakened the amino acid metabolic pathways, and made the anaerobic fermentation cleaner. This study is of great significance for the effective utilization of crop straw resources, the promotion of sustainable livestock production, and the reduction of GHG emissions.

IMPORTANCE
To effectively utilize crop by-product resources, we applied microbial additives to silage fermentation of fresh rice straw. Fresh rice straw is extremely rich in microbial diversity, which was significantly reduced after silage fermentation, and its nutrients were well preserved. Silage fermentation was improved by microbial additives, where the combination of cellulase and lactic acid bacteria acted as enzyme-bacteria synergists to promote lactic acid fermentation and inhibit the proliferation of harmful bacteria, such as protein degradation and gas production, thereby reducing GHG emissions and DM losses. The microbial additives accelerated the formation of a symbiotic microbial network system dominated by lactic acid bacteria, which regulated silage fermentation and improved microbial metabolic pathways for carbohydrates and amino acids, as well as biosynthesis of secondary metabolites.
Optical Spin Initialization of Nitrogen Vacancy Centers in a 28Si-Enriched 6H-SiC Crystal for Quantum Technologies
Authors: Murzakhanov F. F. , Sadovnikova M. A. , Mamin G. V. , Shurtakova D. V. , Mokhov E. N. , Kazarova O. P. , Gafurov M. R. 
Published: June 2024

High-spin defect centers in crystal matrices are used in quantum computing technologies, highly sensitive sensors, and single-photon sources. In this work, optically active nitrogen-vacancy color centers NV– in a 28Si-enriched (nuclear spin $$I = 0$$) 6H-28SiC crystal have been studied using the photoinduced ($$\lambda $$ = 980 nm) high-frequency (94 GHz, 3.4 T) pulsed electron paramagnetic resonance method at a temperature of $$T = 150{\kern 1pt} $$ K. Three structurally nonequivalent types of NV– centers with axial symmetry have been identified and their spectroscopic parameters have been determined. Long spin–lattice, $${{T}_{1}} = 1.3{\kern 1pt} $$ ms, and spin–spin, $${{T}_{2}} = 59{\kern 1pt} $$ μs, ensemble relaxation times of NV– centers with extremely narrow (450 kHz) absorption lines allow highly selective excitation of resonant transitions between sublevels $$({{m}_{I}})$$ caused by the weak hyperfine interaction $$(A \approx 1{\kern 1pt} $$ MHz) with 14N $$(I = 1)$$ nuclei for the quantum manipulation of the electron spin magnetization.
Exploring non-commutativity as a perturbation in the Schwarzschild black hole: quasinormal modes, scattering, and shadows
Authors: Heidari N. , Hassanabadi H. , Filho A. A. Araújo , Kr̆íz̆ J. 
Published: June 2024

AbstractIn this work, by a novel approach to studying the scattering of a Schwarzschild black hole, the non-commutativity is introduced as perturbation. We begin by reformulating the Klein–Gordon equation for the scalar field in a new form that takes into account the deformed non-commutative spacetime. Using this formulation, an effective potential for the scattering process is derived. To calculate the quasinormal modes, we employ the WKB method and also utilize fitting techniques to investigate the impact of non-commutativity on the scalar quasinormal modes. We thoroughly analyze the results obtained from these different methods. Moreover, the greybody factor and absorption cross section are investigated. Additionally, we explore the behavior of null geodesics in the presence of non-commutativity. Specifically, we examine the photonic, and shadow radius as well as the light trajectories for different non-commutative parameters. Therefore, by addressing these various aspects, we aim to provide a comprehensive understanding of the influence of non-commutativity on the scattering of a Schwarzschild-like black hole and its implications for the behavior of scalar fields and light trajectories.
Figure 1 from Oncogenic Cell Tagging and Single-Cell Transcriptomics Reveal Cell Type–Specific and Time-Resolved Responses to <i>Vhl</i> Inactivation in the Kidney
Authors: Kurlekar Samvid , Lima Joanna D.C.C. , Li Ran , Lombardi Olivia , Masson Norma , Barros Ayslan B. , Pontecorvi Virginia , Mole David R. , Pugh Christopher W. , Adam Julie , Ratcliffe Peter J. 
Published: June 2024

<p>A novel reporter model for <i>Vhl</i> inactivation in the mouse kidney. <b>A,</b> Design and recombination of the cell marking conditional <i>Vhl<sup>pjr</sup></i> allele. Double and single arrows indicate reversible and irreversible processes, respectively. <i>Vhl<sup>pjr.fl</sup>, Vhl<sup>pjr.inrec</sup></i>, and <i>Vhl<sup>pjr.KO</sup></i> refer to “floxed,” “incompletely recombined,” and “knockout” forms of the <i>Vhl<sup>pjr</sup></i> allele. P, <i>Vhl</i> promoter; U, untranslated region; E, <i>Vhl</i> exon; I, <i>Vhl</i> intron; pA, polyadenylation site; P2A, porcine teschovirus 2A peptide; SA, splice acceptor. Dashed lines, spliced and translated regions; lightning symbols, excitation and emission wavelengths for tdTomato fluorescence. Red stop sign indicates no interaction between VHL exon 1 fragment and HIFA-1/2 or Elongin B/C. <b>B,</b> Representative tdTomato IHC counterstained with hematoxylin in kidney sections and tdTomato fluorescence-based flow cytometry on renal cells from <i>Vhl<sup>wt/pjr.fl</sup>; Pax8-CreERT2</i> mice untreated (top) or given 5 × 2 mg tamoxifen (TMX; bottom) and harvested at the early time point. Scale bar, 250 μm. Magnification, ×20. FACS gates are shown. <b>C,</b> Gel electrophoresis of genomic PCR for <i>Vhl<sup>wt</sup>, Vhl<sup>pjr.fl</sup></i>, and <i>Vhl<sup>pjr.KO</sup></i> alleles performed on FAC-sorted tdTomato-positive (left) or tdTomato-negative (right) cells from kidneys of <i>Vhl<sup>wt/pjr.fl</sup>; Pax8-CreERT2</i> mice given tamoxifen and harvested at the early time point. <b>D,</b> Representative immunoblots (IB) for HIF1A, HIF2A, or tdTomato protein in tdTomato-negative (−) or tdTomato-positive (+) cells sorted by flow cytometry from dissociated kidneys of <i>Vhl<sup>jae.KO/pjr.fl</sup></i> or <i>Vhl<sup>wt/pjr.fl</sup> Pax8-CreERT2</i> mice given 5 × 2 mg tamoxifen and harvested at the early time point (<i>n</i> = 3 per genotype).</p>
Diet and Tumor Genetics Conspire to Promote Prostate Cancer Metabolism and Shape the Tumor Microenvironment
Authors: Frigo Daniel E. 
Published: June 2024

AbstractObesity has been linked to prostate cancer in a stage-dependent manner, having no association with cancer initiation but correlating with disease progression in men with prostate cancer. Given the rising obesity rate and its association to aggressive prostate cancer, there is a growing need to understand the mechanisms underlying this relationship to identify patients at increased risk of lethal disease and inform therapeutic approaches. In this issue of Cancer Research, Boufaied and colleagues describe how diets high in saturated fatty acids promote MYC-driven prostate cancer. Leveraging MYC-expressing genetically engineered and allograft mouse models fed either a control low-fat or high-fat diet (HFD) enriched in saturated fatty acids, the authors found using digital pathology that HFD-fed mice exhibited increased tumor invasion. Metabolomics, transcriptomics, immunoblotting, and positron emission tomography of tumors from these mice demonstrated that a HFD promoted a metabolic shift in the tumors towards glycolysis. These preclinical data were supported by findings from two large clinical cohorts revealing that men diagnosed with prostate cancer and who consumed high levels of saturated fatty acids possessed tumors bearing glycolytic signatures. Deconvolution analyses and immunohistochemistry validation showed that these tumors also displayed increased angiogenesis and infiltration of immunosuppressive macrophages and regulatory T cells, the latter of which was also correlated with high saturated fat intake–associated glycolytic signatures in patient tumors. Together, these findings suggest that diets rich in saturated fatty acids, rather than obesity alone, accelerate MYC-driven prostate cancers through shifting tumor metabolism and shaping the tumor microenvironment.See related article by Boufaied et al., p. 1834
Pretargeted Radioimmunotherapy with the Novel Anti-oxMIF/HSG Bispecific Antibody ON105 Results in Significant Tumor Regression in Murine Models of Cancer
Authors: Puchol Tarazona Alejandro A. , Schinagl Alexander , Mirkina Irina , Rossmueller Gregor , Kerschbaumer Randolf J. , Bachmann Friedmund , Thiele Michael 
Published: June 2024

Abstract
Radioimmunotherapy (RIT) uses monoclonal antibodies to deliver radionuclides to cancer cells or the tumor microenvironment and has shown promise in treating localized and diffuse tumors. Although RIT agents have gained FDA/EMA approval for certain hematologic malignancies, effectiveness of RIT in treating solid tumors remains limited. In this study, we present PreTarg-it, a novel approach for pretargeted RIT, providing optimized delivery of payloads in a two-step regimen. The effectiveness of PreTarg-it is demonstrated by a powerful combination of ON105, a novel bispecific antibody against both oxidized macrophage migration inhibitory factor (oxMIF) and the histamine-succinyl-glycyl (HSG) hapten, as the first component and the radioactively labeled DOTA-di-HSG peptide as the second component in murine models of cancer. Mice bearing either subcutaneous mouse colorectal CT26 or human pancreatic CFPAC-1 tumors received an i.v. injection of ON105. After ON105 had accumulated in the tumor and cleared from circulation to approximately 1% to 3% of its peak concentration, 177Lu-DOTA-di-HSG peptide was administered. A single PreTarg-it treatment cycle resulted in tumor regression when mice bearing CT26 tumors were given the highest treatment dose with a pretargeting delay of 3 days. Administered with a 5-day interval, the highest dose arrested tumor growth in both CT26 syngrafts and CFPAC-1 xenografts. In all cases, the highest treatment dose resulted in 100% survival at the study endpoint, whereas the control cohorts showed 0% and 60% survival in the CT26 and CFPAC-1 models, respectively. Therefore, PreTarg-it holds potential as a novel and potent therapy for patients with hard-to-treat solid tumors, such as pancreatic cancer, as well as those with late-stage malignancies.
Integrative taxonomy of the groundwater amphipod Niphargus bihorensis Schellenberg, 1940 reveals a species-rich clade
Authors: Stoch Fabio , Knüsel Mara , Zakšek Valerija , Alther Roman , Salussolia Alice , Altermatt Florian , Fišer Cene , Flot Jean-François 
Published: June 2024

Abstract
The genus Niphargus is the most diverse subterranean amphipod genus in the western Palearctic region but, owing to the presence of cryptic species and homoplasy, its taxonomy and biogeographic scenarios are complex, making molecular methods essential to understand its evolution. We conducted a study combining dna-based taxonomy with traditional morphotaxonomy to investigate Niphargus bihorensis Schellenberg, 1940, known from the Western Alps and Carpathians. We redescribed the type material of N. bihorensis from Bihor County, Romania, and revealed the presence of a cryptic species, N. absconditus n. sp., in the same karstic area (Pădurea Craiului Mountains). Additionally, the Alpine populations previously attributed to N. bihorensis turned out to belong to a new, not so closely related species, N. tizianoi n. sp. Phylogenetic analyses based on a concatenated dataset of one mitochondrial and two nuclear markers suggest that the N. bihorensis species complex belongs to a strongly supported clade, together with several species distributed from Switzerland to Iran.
Continent-derived metasediments (Cimes Blanches and Frilihorn) within the ophiolites around Zermatt: relations with the Mischabel backfold and Mont Fort nappe (Pennine Alps)
Authors: Pantet Adrien , Epard Jean-Luc , Masson Henri 
Published: June 2024

AbstractThe region surrounding Zermatt (SW Switzerland and NW Italy) displays some classic examples of imbrications between continental and oceanic units. In particular, the studied units, called Cimes Blanches and Frilihorn or Faisceau Vermiculaire, consist of a set of thin bands of continent-derived metasediments intercalated at different levels within the ocean-derived units. These bands are locally reduced to only one meter thick but can be traced for several tens to more than one hundred kilometers across the Pennine Alps. The mechanisms leading to such imbrications are a long-standing and still-debated question. Based on detailed mapping and structural analysis of key areas, we present new data on the structure and stratigraphy of the Faisceau Vermiculaire in the area surrounding Zermatt, with particular focus on the Täschalpen sector, where the Faisceau Vermiculaire is locally in contact with basement units. Our observations allow: (i) to confirm the presence of widespread breccias of probable Jurassic age in the Faisceau Vermiculaire; (ii) to interpret the contacts between the Faisceau Vermiculaire and the overlying non-ophiolitic Schistes Lustrés (Série Rousse) as stratigraphic; (iii) to show that the stratigraphy of the Faisceau Vermiculaire and associated Série Rousse contrasts strongly with the cover of the Siviez-Mischabel nappe and that these sequences originate from different paleogeographic domains (Prepiemont basin and Briançonnais platform respectively); (iv) to interpret as stratigraphic the contact of the Faisceau Vermiculaire and the Série Rousse with the basement forming the Alphubel anticline; the local unconformity is interpreted as the result of the activity of synsedimentary Jurassic normal paleofaults; (v) to highlight the trace of a major Jurassic normal fault, that should have marked an abrupt thinning of the paleomargin; it corresponds now to the contact between the Faisceau Vermiculaire (and associated Série Rousse) and the Siviez-Mischabel basement in the hinge of the Mischabel backfold. We propose a new tectonic scheme for the structure of the Faisceau Vermiculaire and adjacent units involving an early northward folding of the Faisceau Vermiculaire with the Série Rousse and the ophiolitic Schistes Lustrés of the Tsaté nappe, followed by major backfolding responsible for the southward emplacement of these units above the HP Zermatt-Saas and Monte Rosa nappes. Our study at regional scale shows that the group formed by the Alphubel basement, the Faisceau Vermiculaire and the Série Rousse share a tectonic position and stratigraphic sequences identical to those of the Mont Fort nappe, which outcrops on the other side of the Dent Blanche klippe. It leads to the proposition that this group constitutes the eastern extension of the Mont Fort nappe.
Rab3B enhances the stabilization of DDX6 to promote lung adenocarcinoma aggressiveness
Authors: Yao Guodong , Yu Shan , Hou Feng , Xiao Zunyu , Li Guangqi , Ji Xiaobin , Wang Jigang 
Published: June 2024

Abstract
Background
Liver kinase B1 (LKB1) is frequently mutated in lung adenocarcinoma, and its loss contributes to tumor progression.

Methods
To identify LKB1 downstream genes that promote lung adenocarcinoma aggressiveness, we performed bioinformatical analysis using publicly available datasets.

Results
Rab3B was upregulated in LKB1-depleted lung adenocarcinoma cells and suppressed by LKB1 overexpression. CREB protein was enriched at the promoter of Rab3B in lung cancer cells. Silencing of CREB abrogated the upregulation of Rab3B upon LKB1 loss. Immunohistochemistry revealed the elevated expression of Rab3B in lung adenocarcinomas relative to adjacent normal tissues. Upregulation of Rab3B was significantly associated with lymph node metastasis, advanced tumor stage, and reduced overall survival in lung adenocarcinoma patients. Knockdown of Rab3B suppressed and overexpression of Rab3B promoted the proliferation, colony formation, and migration of lung adenocarcinoma cells in vitro. In a mouse xenograft model, Rab3B depletion restrained and Rab3B overexpression augmented the growth of lung adenocarcinoma tumors. Mechanistically, Rab3B interacted with DDX6 and enhanced its protein stability. Ectopic expression of DDX6 significantly promoted the proliferation, colony formation, and migration of lung adenocarcinoma cells. DDX6 knockdown phenocopied the effects of Rab3B depletion on lung adenocarcinoma cells. Additionally, DDX6 overexpression partially rescued the aggressive phenotype of Rab3B-depleted lung adenocarcinoma cells.

Conclusion
LKB1 deficiency promotes Rab3B upregulation via a CREB-dependent manner. Rab3B interacts with and stabilizes DDX6 protein to accelerate lung adenocarcinoma progression. The Rab3B-DDX6 axis may be potential therapeutic target for lung adenocarcinoma.
The effectiveness of the 0.19 mg fluocinolone acetonide implant in treating non-infectious posterior uveitis: a real-world experience
Authors: Kozak Igor , Gurbaxani Avinash , Pandova Maya 
Published: June 2024

Abstract
Background
The 0.19 mg fluocinolone acetonide (FAc) implant (ILUVIEN) has been approved for prevention of relapse in recurrent non-infectious uveitis affecting the posterior segment of the eye (NIU-PS). There is little data assessing the long-term efficacy and safety of the FAc implant in this indication. Therefore, we conducted a retrospective interventional case review of 18 eyes from 13 patients with NIU-PS treated with the FAc implant at three ophthalmology departments in the Middle East between 2018 and 2021.

Main text
Baseline patient characteristics, including best-corrected visual acuity (BCVA), central retinal thickness (CRT) and intraocular pressure (IOP), were collected at the time of FAc implant administration and at 1–3 months, 6 months and every six months thereafter. The mean time of follow-up was 29.7 ± 14.6 (mean ± SD) months. Over the follow-up, the BCVA significantly increased from month 1 (P = 0.002) until month 36 (P = 0.024) and remained improving throughout the follow-up period (P = 0.004). The CRT significantly decreased from month 1 (P = 0.008) until month 12 (P = 0.003) and was persistently lower during the follow-up period (P = 0.022). Significant improvements in anterior chamber cells (P = 0.004) and vitritis scores (P = 0.001) were observed by Month 6. Similarly, at Month 12, significant improvements were noted in both parameters as well (anterior chamber cells: P = 0.012; vitritis scores: P = 0.004). Mean IOP remained relatively stable throughout (P = 0.205) the follow-up.

Conclusions
Our results suggest improvements and long-term maintenance in functional and anatomical outcomes with FAc implant with a manageable safety profile in a real-world clinical setting in patients with NIU-PS.