bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of mineral and non-mineral sources of iron and sulfur on the metalloproteome of
Methanosarcina barkeri
Authors: Larson James , Tokmina-Lukaszewska Monika , Payne Devon , Spietz Rachel L. , Fausset Hunter , Alam Md Gahangir , Brekke Brooklyn K. , Pauley Jordan , Hasenoehrl Ethan J. , Shepard Eric M. , Boyd Eric S. , Bothner Brian 
Published: July 2024

ABSTRACT

Methanogens often inhabit sulfidic environments that favor the precipitation of transition metals such as iron (Fe) as metal sulfides, including mackinawite (FeS) and pyrite (FeS
2
). These metal sulfides have historically been considered biologically unavailable. Nonetheless, methanogens are commonly cultivated with sulfide (HS
-
) as a sulfur source, a condition that would be expected to favor metal precipitation and thus limit metal availability. Recent studies have shown that methanogens can access Fe and sulfur (S) from FeS and FeS
2
to sustain growth. As such, medium supplied with FeS
2
should lead to higher availability of transition metals when compared to medium supplied with HS
-
. Here, we examined how transition metal availability under sulfidic (i.e., cells provided with HS
-
as sole S source) versus non-sulfidic (cells provided with FeS
2
as sole S source) conditions impact the metalloproteome of
Methanosarcina barkeri
Fusaro. To achieve this, we employed size exclusion chromatography coupled with inductively coupled plasma mass spectrometry and shotgun proteomics. Significant changes were observed in the composition and abundance of iron, cobalt, nickel, zinc, and molybdenum proteins. Among the differences were alterations in the stoichiometry and abundance of multisubunit protein complexes involved in methanogenesis and electron transport chains. Our data suggest that
M. barkeri
utilizes the minimal iron-sulfur cluster complex and canonical cysteine biosynthesis proteins when grown on FeS
2
but uses the canonical Suf pathway in conjunction with the tRNA-Sep cysteine pathway for iron-sulfur cluster and cysteine biosynthesis under sulfidic growth conditions.

IMPORTANCE

Proteins that catalyze biochemical reactions often require transition metals that can have a high affinity for sulfur, another required element for life. Thus, the availability of metals and sulfur are intertwined and can have large impacts on an organismismal biochemistry. Methanogens often occupy anoxic, sulfide-rich (euxinic) environments that favor the precipitation of transition metals as metal sulfides, thereby creating presumed metal limitation. Recently, several methanogens have been shown to acquire iron and sulfur from pyrite, an abundant iron-sulfide mineral that was traditionally considered to be unavailable to biology. The work presented here provides new insights into the distribution of metalloproteins, and metal uptake of
Methanosarcina barkeri
Fusaro grown under euxinic or pyritic growth conditions. Thorough characterizations of this methanogen under different metal and sulfur conditions increase our understanding of the influence of metal availability on methanogens, and presumably other anaerobes, that inhabit euxinic environments.
Nondestructive and three-dimensional visualization by identifying elements using synchrotron radiation microscale X-ray CT reveals microbial and cavity distributions in anaerobic granular sludge
Authors: Urasaki Kampachiro , Morono Yuki , Uramoto Go-Ichiro , Uesugi Kentaro , Yasutake Masahiro , Akishiba Manato , Guo Guangze , Li Yu-You , Kubota Kengo 
Published: July 2024

ABSTRACT

We developed a nondestructive three-dimensional microbial visualization method utilizing synchrotron radiation X-ray microscale computed tomography to better understand the relationship between microorganisms and their surrounding habitats. The method was tested and optimized using a mixture of axenic
Escherichia coli
and
Comamonas testosteroni
. The osmium-thiocarbohydrazide-osmium method was used to stain all the microbial cells, and gold
in situ
hybridization was used to detect specific phylogenetic microbial groups. The stained samples were embedded in epoxy resin for microtomographic analysis. Differences in X-ray absorbances were calculated by subtracting the pre-L
3
-edge images from the post-L
3
-edge images to visualize the osmium and gold signals. Although we successfully detected cells stained with osmium, those labeled with gold were not detected, probably because of the insufficient density of gold atoms in the microbial cells. We then applied the developed technique to anaerobic granules and visualized the distribution of microbial cells and extracellular polymeric substances. Empty spaces were highlighted to determine the cavity distribution in granules. Numerous independent cavities of different sizes were identified in the granules. The developed method can be applied to various environmental samples for deeper insights into microbial life in their habitats.

IMPORTANCE

Microorganisms inhabit diverse environments and often form biofilms. One factor that affects their community structure is the surrounding physical environment. The arrangement of residential space within the formed biofilm plays a crucial role in the supply and transportation of substances, as well as the discharge of metabolites. Conventional approaches, such as scanning electron microscopy and confocal laser scanning microscopy combined with fluorescence in
situ
hybridization, have limitations as they provide information primarily from the biofilm surface and cross-sections. In this study, we developed a method for detecting microorganisms in biofilms using synchrotron radiation X-ray microscale computer tomography. The developed method allows nondestructive three-dimensional observation of biofilms at a single-cell resolution (voxel size of approximately 200 nm), facilitating an understanding of the relationship between microorganisms and their physical habitats.
Virus-like particles displaying the mature C-terminal domain of filamentous hemagglutinin are immunogenic and protective against
Bordetella pertussis
respiratory infection in mice
Authors: Pyles Gage M. , Huckaby Annalisa B. , Gutierrez Maria de la Paz , Witt William T. , Mateu-Borrás Margalida , Dublin Spencer R. , Rocuskie-Marker Carleena , Sesti Bethany N. , Peasak Kerrington , Bitzer Graham J. , Rader Nathaniel , Weaver Kelly L. , Boehm Dylan T. , Fitzgerald Nicholas , Chapman Joshua , Ulicny Samuel , Damron F. Heath , Barbier Mariette 
Published: July 2024

ABSTRACT

Bordetella pertussis,
the bacterium responsible for whooping cough, remains a significant public health challenge despite the existing licensed pertussis vaccines. Current acellular pertussis vaccines, though having favorable reactogenicity and efficacy profiles, involve complex and costly production processes. In addition, acellular vaccines have functional challenges such as short-lasting duration of immunity and limited antigen coverage. Filamentous hemagglutinin (FHA) is an adhesin of
B. pertussis
that is included in all multivalent pertussis vaccine formulations. Antibodies to FHA have been shown to prevent bacterial attachment to respiratory epithelial cells, and T cell responses to FHA facilitate cell-mediated immunity. In this study, FHA’s mature C-terminal domain (MCD) was evaluated as a novel vaccine antigen. MCD was conjugated to virus-like particles via SpyTag-SpyCatcher technology. Prime-boost vaccine studies were performed in mice to characterize immunogenicity and protection against the intranasal
B. pertussis
challenge. MCD-SpyVLP was more immunogenic than SpyTag-MCD antigen alone, and in Tohama I strain challenge studies, improved protection against challenge was observed in the lungs at day 3 and in the trachea and nasal wash at day 7 post-challenge. Furthermore, a
B. pertussis
strain encoding genetically inactivated pertussis toxin was used to evaluate MCD-SpyVLP vaccine immunity. Mice vaccinated with MCD-SpyVLP had significantly lower respiratory bacterial burden at both days 3 and 7 post-challenge compared to mock-vaccinated animals. Overall, these data support the use of SpyTag-SpyCatcher VLPs as a platform for use in vaccine development against
B. pertussis
and other pathogens.
Draft genome sequencing of
Pediococcus acidilactici
strains isolated from cow’s milk: unlocking insights into functional traits and applications
Authors: Siddique Naim , Rahman Md. Morshedur , Akter Salma , Hasan Mehedi Mahmudul , Das Ziban Chandra , Hoque M. Nazmul 
Published: July 2024

ABSTRACT

Pediococcus acidilactici
is a potential probiotic bacteria isolated from diverse sources. However, strains isolated from milk, especially from raw milk of healthy cows, have not been thoroughly studied. Here, we report the draft genome sequence of
P. acidilactici
strains MBBL5 and MBBL7, isolated from milk samples of healthy cows.
Integrative
in vivo
analysis of the ethanolamine utilization bacterial microcompartment in
Escherichia coli
Authors: Jallet Denis , Soldan Vanessa , Shayan Ramteen , Stella Alexandre , Ismail Nour , Zenati Rania , Cahoreau Edern , Burlet-Schiltz Odile , Balor Stéphanie , Millard Pierre , Heux Stéphanie 
Published: July 2024

ABSTRACT

Bacterial microcompartments (BMCs) are self-assembling protein megacomplexes that encapsulate metabolic pathways. Although approximately 20% of sequenced bacterial genomes contain operons encoding putative BMCs, few have been thoroughly characterized, nor any in the most studied
Escherichia coli
strains. We used an interdisciplinary approach to gain deep molecular and functional insights into the ethanolamine utilization (Eut) BMC system encoded by the
eut
operon in
E. coli
K-12. The
eut
genotype was linked with the ethanolamine utilization phenotype using deletion and overexpression mutants. The subcellular dynamics and morphology of the
E. coli
Eut BMCs were characterized
in cellula
by fluorescence microscopy and electron (cryo)microscopy. The minimal proteome reorganization required for ethanolamine utilization and the
in vivo
stoichiometric composition of the Eut BMC were determined by quantitative proteomics. Finally, the first flux map connecting the Eut BMC with central metabolism
in cellula
was obtained by genome-scale modeling and
13
C-fluxomics. Our results reveal that contrary to previous suggestions, ethanolamine serves both as a nitrogen and a carbon source in
E. coli
K-12, while also contributing to significant metabolic overflow. Overall, this study provides a quantitative molecular and functional understanding of the BMCs involved in ethanolamine assimilation by
E. coli
.

IMPORTANCE

The properties of bacterial microcompartments make them an ideal tool for building orthogonal network structures with minimal interactions with native metabolic and regulatory networks. However, this requires an understanding of how BMCs work natively. In this study, we combined genetic manipulation, multi-omics, modeling, and microscopy to address this issue for Eut BMCs. We show that the Eut BMC in
Escherichia coli
turns ethanolamine into usable carbon and nitrogen substrates to sustain growth. These results improve our understanding of compartmentalization in a widely used bacterial chassis.
Covid-19 infection and vaccination during first trimester and risk of congenital anomalies: Nordic registry based study
Authors: Magnus Maria C , Söderling Jonas , Örtqvist Anne K , Andersen Anne-Marie Nybo , Stephansson Olof , Håberg Siri E , Urhoj Stine Kjaer 
Published: July 2024

Abstract

Objectives
To evaluate the risk of major congenital anomalies according to infection with or vaccination against covid-19 during the first trimester of pregnancy.

Design
Prospective Nordic registry based study.

Setting
Sweden, Denmark, and Norway.

Participants
343 066 liveborn singleton infants in Sweden, Denmark, and Norway, with an estimated start of pregnancy between 1 March 2020 and 14 February 2022, identified using national health registries.

Main outcome measure
Major congenital anomalies were categorised using EUROCAT (European Surveillance of Congenital Anomalies) definitions. The risk after covid-19 infection or vaccination during the first trimester was assessed by logistic regression, adjusting for maternal age, parity, education, income, country of origin, smoking, body mass index, chronic conditions, and estimated date of start of pregnancy.

Results
17 704 (5.2%) infants had a major congenital anomaly. When evaluating risk associated with covid-19 infection during the first trimester, the adjusted odds ratio ranged from 0.84 (95% confidence interval 0.51 to 1.40) for eye anomalies to 1.12 (0.68 to 1.84) for oro-facial clefts. Similarly, the risk associated with covid-19 vaccination during the first trimester ranged from 0.84 (0.31 to 2.31) for nervous system anomalies to 1.69 (0.76 to 3.78) for abdominal wall defects. Estimates for 10 of 11 subgroups of anomalies were less than 1.04, indicating no notable increased risk.

Conclusions
Covid-19 infection and vaccination during the first trimester of pregnancy were not associated with risk of congenital anomalies.
Effect of Ho3+ Doping on Structural and Magnetic Properties of Multiferroic YbMnO3
Authors: Kishore Yadav Nand , K. Damodar Reddy , D. Swathi , R. Nagaraju , P. Sowjanya , K. N. Prasanna Kumari , N. Kumar Swamy , T. Ramesh , N. Pavan Kumar 
Published: July 2024

Using the traditional solid-state reaction approach, multiferroic ceramics with the compositional formula Yb1−xHoxMnO3, where x = 0 to 0.4 with 0.1 variation were synthesized. The structural and magnetic properties of the prepared poly-crystalline samples Yb1−xHoxMnO3 were investigated to show the effect of higher magnetic moment Ho3+ ion over the Yb ion. X-ray diffraction was used to analyze the compound’s crystal structure and confirm that they have a hexagonal single-phase structure with a P6
3
cm space group. The presence of functional groups and their shifting to lower frequency regions were revealed by Fourier-transform infrared spectroscopy. UV–vis absorbance spectra were used to calculate the energy gap values, and the resultant data shows a decrease in band gap values with an increase in Ho3+ doping. Crystal deformation with the doping of Ho3+ was observed using Raman spectra. Room-temperature magnetic studies were used to reveal the paramagnetic nature of the samples and the increase in magnetic parameters due to the doping of the higher magnetic moment Ho3+ ion.
Influence of Zinc Manganite Nano Fillers on the Optical and Dielectric Features of Poly-Methyl Methacrylate/Multi-Walled Carbon Nanotubes Nanocomposites
Authors: El-Naggar A. M. , Heiba Zein K. , Kamal A. M. , Ibrahim R. M. , Mohamed Mohamed Bakr 
Published: July 2024

Poly (methyl methacrylate, PMMA)/ multi-walled carbon nanotubes (MWCNTs)/ x wt %zinc manganite (ZnMn2O4) polymers were fabricated using co-precipitation and casting techniques. The structure of the filler and all polymers was determined with X-ray diffraction. The morphology of the polymer surfaces was explored by employing scanning electron microscopy. The direct and indirect band gap energies (E
g) of PMMA polymer (5.02, 4.44) eV decreased attaining minimum values (4.97, 3.41) eV upon the addition of MWCNTs and 2 wt% ZnMn2O4. The refractive index at 600 nm was increased from 1.33 (PMMA) to 1.55 (x = 2 wt% ZnMn2O4). The optical dielectric constant and optical conductivity displayed their highest values when the ZnMn2O4 doping level reached 2 wt%. The PMMA/MWCNTs/x wt% ZnMn2O4 polymers exhibited blue-violet colors on the CIE 1931 chromaticity diagram under excitation wavelength of 317 nm. The electrical dielectric constant and the AC conductivity attained their peak at the concentration of 2 wt% and 1 wt% ZnMn2O4, respectively. PMMA/MWCNTs/x wt% ZnMn2O4 polymers possess controllable optical and electrical characteristics, thus making them potentially valuable optical materials for future optoelectronic or photocatalytic application development.
Targeting Cholesterol Biosynthesis with Statins Synergizes with AKT Inhibitors in Triple-Negative Breast Cancer
Authors: Hillis Alissandra L. , Martin Timothy D. , Manchester Haley E. , Högström Jenny , Zhang Na , Lecky Emmalyn , Kozlova Nina , Lee Jonah , Persky Nicole S. , Root David E. , Brown Myles , Cichowski Karen , Elledge Stephen J. , Muranen Taru , Fruman David A. , Barry Simon T. , Clohessy John G. , Madsen Ralitsa R. , Toker Alex 
Published: July 2024

Abstract
Triple-negative breast cancer (TNBC) is responsible for a disproportionate number of breast cancer patient deaths due to extensive molecular heterogeneity, high recurrence rates, and lack of targeted therapies. Dysregulation of the phosphoinositide 3-kinase (PI3K)/AKT pathway occurs in approximately 50% of TNBC patients. Here, we performed a genome-wide CRISPR/Cas9 screen with PI3Kα and AKT inhibitors to find targetable synthetic lethalities in TNBC. Cholesterol homeostasis was identified as a collateral vulnerability with AKT inhibition. Disruption of cholesterol homeostasis with pitavastatin synergized with AKT inhibition to induce TNBC cytotoxicity in vitro in mouse TNBC xenografts and in patient-derived estrogen receptor (ER)–negative breast cancer organoids. Neither ER-positive breast cancer cell lines nor ER-positive organoids were sensitive to combined AKT inhibitor and pitavastatin. Mechanistically, TNBC cells showed impaired sterol regulatory element-binding protein 2 (SREBP-2) activation in response to single-agent or combination treatment with AKT inhibitor and pitavastatin, which was rescued by inhibition of the cholesterol-trafficking protein Niemann-Pick C1 (NPC1). NPC1 loss caused lysosomal cholesterol accumulation, decreased endoplasmic reticulum cholesterol levels, and promoted SREBP-2 activation. Taken together, these data identify a TNBC-specific vulnerability to the combination of AKT inhibitors and pitavastatin mediated by dysregulated cholesterol trafficking. These findings support combining AKT inhibitors with pitavastatin as a therapeutic modality in TNBC.
Significance: Two FDA-approved compounds, AKT inhibitors and pitavastatin, synergize to induce cell death in triple-negative breast cancer, motivating evaluation of the efficacy of this combination in clinical trials.
The Innate Immune Landscape of dMMR/MSI Cancers Predicts the Outcome of Nivolumab Treatment: Results from the Drug Rediscovery Protocol
Authors: Zeverijn Laurien J. , Geurts Birgit S. , Battaglia Thomas W. , van Berge Henegouwen Jade M. , de Wit Gijs F. , Hoes Louisa R. , van der Wijngaart Hanneke , van der Noort Vincent , Roepman Paul , de Leng Wendy W.J. , Jansen Anne M.L. , Chalabi Myriam , van Herpen Carla M.L. , Devriese Lot A. , Erdkamp Frans L.G. , Labots Mariette , de Jonge Maja J.A. , Kerver Emile D. , Bins Adriaan D. , Leek Lindsay V.M. , Notohardjo Jessica C.L. , van den Eertwegh Alfonsus J.M. , Wessels Lodewyk F.A. , Verheul Henk M.W. , Gelderblom Hans , van de Haar Joris , Voest Emile E. 
Published: July 2024

Abstract

Purpose:
The treatment efficacy of nivolumab was evaluated in patients with advanced, treatment-refractory solid mismatch repair deficiency/microsatellite-instable (dMMR/MSI) tumors, and in-depth biomarker analyses were performed to inform precision immunotherapy approaches.

Patients and Methods:
Patients with dMMR/MSI tumors who exhausted standard-of-care treatment options were enrolled in the Drug Rediscovery Protocol, a pan-cancer clinical trial that treats patients with cancer based on their tumor molecular profile with off-label anticancer drugs (NCT02925234). Patients received nivolumab (four cycles of 240 mg every 2 weeks, thereafter 480 mg every 4 weeks). The primary endpoint was clinical benefit (CB: objective response or stable disease ≥16 weeks). Whole-genome sequencing and RNA sequencing were performed on pretreatment tumor biopsies.

Results:
A total of 130 evaluable patients were enrolled with 16 different cancer types. CB was observed in 62% [95% confidence interval (CI), 53–70], with an objective response in 45% (95% CI, 36–54). After a median follow-up of 14.5 months (95% CI, 13–19), the median progression-free survival was 18 months (95% CI, 9–not reached), and the median overall survival was not reached. Whereas CB was not, or only weakly, associated with markers of adaptive immune cell infiltration, CB was strongly associated with expression of a broad set of innate immune receptors/ligands. This clearly contrasted findings in melanoma, in which markers of adaptive immunity dominated the biomarker landscape.

Conclusions:
Nivolumab proved highly effective in advanced dMMR/MSI tumors. Expression of key innate immune receptors/ligands was the main predictor of a good treatment outcome, contrasting findings in melanoma and strengthening the rationale for tumor type–specific biomarkers for guiding immunotherapy.
Spatial Contextual Information Modulates Affordance Processing and Early Electrophysiological Markers of Scene Perception
Authors: Naveilhan Clément , Saulay-Carret Maud , Zory Raphaël , Ramanoël Stephen 
Published: July 2024

Abstract
Scene perception allows humans to extract information from their environment and plan navigation efficiently. The automatic extraction of potential paths in a scene, also referred to as navigational affordance, is supported by scene-selective regions (SSRs) that enable efficient human navigation. Recent evidence suggests that the activity of these SSRs can be influenced by information from adjacent spatial memory areas. However, it remains unexplored how this contextual information could influence the extraction of bottom–up information, such as navigational affordances, from a scene and the underlying neural dynamics. Therefore, we analyzed ERPs in 26 young adults performing scene and spatial memory tasks in artificially generated rooms with varying numbers and locations of available doorways. We found that increasing the number of navigational affordances only impaired performance in the spatial memory task. ERP results showed a similar pattern of activity for both tasks, but with increased P2 amplitude in the spatial memory task compared with the scene memory. Finally, we reported no modulation of the P2 component by the number of affordances in either task. This modulation of early markers of visual processing suggests that the dynamics of SSR activity are influenced by a priori knowledge, with increased amplitude when participants have more contextual information about the perceived scene. Overall, our results suggest that prior spatial knowledge about the scene, such as the location of a goal, modulates early cortical activity associated with SSRs, and that this information may interact with bottom–up processing of scene content, such as navigational affordances.
Assessing the Impact of Transcranial Magnetic Stimulation on Speech Perception in Noise
Authors: Brisson Valérie , Tremblay Pascale 
Published: July 2024

Abstract
Healthy aging is associated with reduced speech perception in noise (SPiN) abilities. The etiology of these difficulties remains elusive, which prevents the development of new strategies to optimize the speech processing network and reduce these difficulties. The objective of this study was to determine if sublexical SPiN performance can be enhanced by applying TMS to three regions involved in processing speech: the left posterior temporal sulcus, the left superior temporal gyrus, and the left ventral premotor cortex. The second objective was to assess the impact of several factors (age, baseline performance, target, brain structure, and activity) on post-TMS SPiN improvement. The results revealed that participants with lower baseline performance were more likely to improve. Moreover, in older adults, cortical thickness within the target areas was negatively associated with performance improvement, whereas this association was null in younger individuals. No differences between the targets were found. This study suggests that TMS can modulate sublexical SPiN performance, but that the strength and direction of the effects depend on a complex combination of contextual and individual factors.