bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the Common Mutational Landscape in Cutaneous Melanoma and Pancreatic Cancer
Authors: Broseghini Elisabetta , Venturi Federico , Veronesi Giulia , Scotti Biagio , Migliori Marina , Marini Desy , Ricci Claudio , Casadei Riccardo , Ferracin Manuela , Dika Emi 
Published: November 2024

ABSTRACTCutaneous melanoma (CM) and pancreatic cancer are aggressive tumors whose incidences are rapidly increasing in the last years. This review aims to provide a complete and update description about mutational landscape in CM and pancreatic cancer, focusing on similarities of these two apparently so different tumors in terms of site, type of cell involved, and embryonic origin. The familial forms of CM and pancreatic cancers are often characterized by a common mutated gene, namely CDKN2A. In fact, a germline mutation in CDKN2A gene can be responsible for the development of the familial atypical multiple mole and melanoma syndrome (FAMMM), which is characterized by melanomas and pancreatic cancer development. Sporadic melanoma and pancreatic cancer showed different key‐driven genes. The open‐access resource cBioPortal has been explored to deepen and investigate the common mutational landscape of these two tumors. We investigated the common mutated genes found in both melanoma and pancreatic cancer with a frequency of at least 5% of tested patients and copy number alterations with a frequency of at least of 3%. Data showed that 18 mutated genes and 3 copy number alterations are present in both melanoma and pancreatic cancers types. Since we found two patients that developed both melanoma and pancreatic cancer, we compared mutation landscape between the two tumors and identified a pathogenic variant in BRCA2 gene. This review gives valuable insights into the genetic underpinnings of melanoma and pancreatic cancer, urging the continued exploration and research of new genetic biomarkers able to identify patients and families at high risk of developing both cancers and to address to screening and to an effective clinical management of the patient.
Salmon Aquaculture in Chile: Production Growth and Socioeconomic Impacts
Authors: Ceballos‐Concha Adams , Asche Frank , Cárdenas‐Retamal Roberto 
Published: November 2024

ABSTRACTGlobal aquaculture production has been rapidly increasing in recent decades. Associated with this growth, there has been a discussion with respect to the industry's socioeconomic impact. In particular, the industry's ability to make a positive difference in the communities where it is conducted is often questioned. This is a difficult topic to address due to limited data availability. However, it is a critical question concerning the aquaculture industry's long‐term viability. Some recent studies have addressed specific indicators such as poverty reduction in a given country. However, no studies review the impact of an aquaculture industry on a broad set of indicators over time. In this paper, we review the impact of the Chilean salmon industry on three broad socioeconomic indicators: employment, salary level and migration; as well as several narrower indicators. While data beyond production initially are scarce and mostly found in the gray literature, the information they provide connects well with newer data sets as they become available. Not unexpectedly, employment in the Chilean aquaculture industry increases with production. The industry pays relatively well, and it has a societal impact as opportunities created by the industry first reverse outward migration and then lead to inward migration. This is also associated with reduced poverty, a more even income distribution, a higher female labor participation ratio, and higher education levels. While the overall socioeconomic impacts of the industry are positive, they are also disrupted by severe environmental crises and show that the socioeconomic benefits are conditioned on environmental sustainability.
Susceptibility of Mammals to Highly Pathogenic Avian Influenza: A Qualitative Risk Assessment From the Belgian Perspective
Authors: Van Leeuw Virginie , Depoorter Pieter , Mauroy Axel , Beck Olivier , Claeys Herman , De Regge Nick , De Waele Valérie , De Winter Paul , Heymans Jean‐François , Hooyberghs Jozef , Houdart Philippe , Houtsaeger Cyrelle , Linden Annick , Mori Marcella , Nauwynck Hans , Parys Anna , Rebolledo Romero Javiera , Rettigner Chantal , Rouffaer Lieze , Stassijns Jorgen , Steensels Mieke , Van Gucht Steven , Van Reeth Kristien , Vermeersch Katie , Vervaeke Muriel , Saegerman Claude , Dewulf Jeroen 
Published: November 2024

ABSTRACTAimsThe world experienced a huge number of outbreaks of highly pathogenic avian influenza (HPAI) in birds, which could represent one of the largest registered epidemics of infectious disease in food‐producing animals. Therefore, mammals, including humans, are continuously exposed to HPAI viruses leading to sporadic and sometimes unusual mammal infections. The aim of this paper is to assess the risk of crossing the avian/mammalian species barrier by the currently circulating HPAI viruses, focusing on the epidemiological situation of Belgium, a representative country for Western Europe.Methods and ResultsInformation on transmission pathways and species susceptibility, based on the experimental and epidemiological data, was reviewed and weighted to assess the risk of mammal infection with HPAI A(H5N1) viruses of the circulating clade 2.3.4.4b. This risk is defined as the likelihood of mammal infection by birds crossed by the clinical consequences of this infection for this animal. From the Belgian perspective, it is concluded that this risk remains ‘low’ to ‘moderate’ for captive/domestic mammal species. However, this risk was categorised as ‘high’ for certain species, i.e. mammals that have the opportunity to have frequent direct or indirect close contacts with infected (dead) birds, such as wild felids, wild mustelids, foxes and wild marine carnivore mammals. For some mammal species, the uncertainty associated with the assessment remains high due to an ever‐changing situation.ConclusionsThe longer the virus will continue to circulate in wildlife/the environment the stronger the probability of contact between infected birds and mammals will become. This will increase the related risk of viral adaptation for efficient transmission between mammal, posing concerns for public health. Regular reassessments based on the field and experimental data are therefore necessary to implement and adapt risk‐based mitigation measures. This will require continuous monitoring of avian influenza viruses in both birds and mammals as well as sharing of sequence data.
The effect of female breast surface area on cutaneous thermal sensation, wetness perception and epidermal properties
Authors: Blount Hannah , Valenza Alessandro , Ward Jade , Caggiari Silvia , Worsley Peter R. , Filingeri Davide 
Published: November 2024

AbstractFemale development includes significant size changes across the breast. Yet, whether differences in breast surface area (BrSA) modify breast sensitivity to warm, cold and wetness, and the associated epidermal properties (skin thickness and surface roughness) remain unclear. We investigated the relationship between BrSA and thermal and wetness perception, as well as epidermal properties, in 21 females (2810 years) of varying breast sizes (BrSA range: 147–502 cm2), at multiple breast sites (i.e., nipple, above and below the nipple, and bra triangle). Associations between BrSA and the perceptual and epidermal variables were determined via correlation analyses. Differences across test sites were assessed by repeated‐measures ANOVA. Our results did not support the hypothesis that larger breasts present reduced thermal and wetness sensitivity, except for the above nipple site, which presented reduced warm sensitivity with increasing BrSA (r = −0.61, P = 0.003). We also found a heterogeneous distribution of cold, but not warm or wetness, sensitivity across the breast, with the above nipple site presenting lower cold sensitivity than any other site (P < 0.015). Our findings did not indicate any association between BrSA and epidermal properties (thickness and roughness), nor any site‐dependent variation in these anatomical parameters (P > 0.15). We conclude that, while some skin‐site (i.e., above the nipple) and perceptual modality‐dependent (i.e., warm sensitivity) differences were observed, BrSA‐dependent variations in thermal and wetness sensitivity were not a generalised feature of the skin covering the breast. These observations advance our fundamental understanding of breast sensory function, and they could inform the design of user‐centred clothing such as bras.
Rad‐mediated inhibition of CaV1.2 channel activity contributes to uterine artery haemodynamic adaptation to pregnancy
Authors: Hu Xiang‐Qun , Song Rui , Dasgupta Chiranjib , Liu Taiming , Zhang Meijuan , Twum‐Barimah Stephen , Blood Arlin B. , Zhang Lubo 
Published: November 2024

AbstractThe striking increase of uterine blood flow during pregnancy is essential for normal fetal development as well as for cardiovascular well‐being of the mother. Yet, the underlying mechanisms of pregnancy‐mediated vasodilatation of the uterine artery are not fully understood. In this study, we test the hypothesis that Rad, a monomeric G protein, is a novel regulatory mechanism in inhibiting CaV1.2 channel currents in uterine artery haemodynamic adaptation to pregnancy in a sheep model. We found that pregnancy significantly upregulates Rad expression and decreases CaV1.2 channel currents in uterine arterial smooth muscle cells. Rad knockdown ex vivo and in vivo increases CaV1.2 activity and channel window currents by reducing steady‐state inactivation in uterine arteries of pregnant sheep, recapitulating the phenotype of uterine arteries in non‐pregnant animals. Moreover, Rad knockdown in vivo in pregnant sheep enhances myogenic tone and phenylephrine‐induced vasoconstriction of uterine arteries. Whereas knockdown of Rad has no effect on mesenteric arterial CaV1.2 channel activity and mean arterial blood pressure, it significantly increases uterine vascular resistance and decreases uterine artery blood flow. Our study reveals a novel cause‐and‐effect mechanism of Rad in pregnancy‐induced suppression of CaV1.2 channel activity in uterine arteries to facilitate increased uterine blood flow, providing new insights into fundamental mechanisms of uterine haemodynamic adaptation to pregnancy.
imageKey points
Pregnancy suppresses CaV1.2 channel currents in uterine arterial smooth muscle cells.
Rad, a monomeric G protein, is upregulated in uterine arteries of pregnant sheep.
Rad knockdown ex vivo or in vivo increases CaV1.2 channel currents in uterine arteries from pregnant ewes.
In vivo knockdown of Rad elevates uterine vascular resistance and decreases uterine blood flow in pregnant sheep.
The study reveals a novel mechanism of Rad in pregnancy‐induced suppression of CaV1.2 channel activity in uterine arterial haemodynamic adaptation to pregnancy.
Clinical evaluation of advanced MALDI-TOF MS for carbapenemase subtyping in Gram-negative isolates
Authors: Cheon Dong Huey , Jang Heejung , Choi Yoon Kyung , Oh Won Seok , Hwang Seohyun , Park Ju-Ri , Kim Hyojin , Park Yoonha , Lee Saeyoung , Yang Won Suk , Kim Min Jin , Lee Sun Hwa , Baek Je-Hyun 
Published: November 2024

ABSTRACT

The spread of carbapenemase-producing Enterobacterales (CPE) is emerging as a significant clinical concern in tertiary hospitals and, in particular, long-term care facilities with deficiencies in infection control. This study aims to evaluate an advanced matrix-assisted laser desorption/ionization (A-MALDI) mass spectrometry method for the identification of carbapenemases and further discrimination of their subtypes in clinical isolates. The A-MALDI method was employed to detect CPE target proteins. Enhancements were made to improve detectability and mass accuracy through the optimization of MALDI-TOF settings and internal mass calibration. A total of 581 clinical isolates were analyzed, including 469 CPE isolates (388
Klebsiella pneumoniae
carbapenemases [KPC], 51 NDM, 40 OXA, and 2 GES) and 112 carbapenemase-negative isolates. Clinical evaluation of the A-MALDI demonstrated 100% accuracy and precision in identifying all the collected CPE isolates. Additionally, A-MALDI successfully discriminated individual carbapenemase subtypes (KPC-2 or KPC-3/KPC-4, OXA-48 or OXA-181 or OXA-232, GES-5 or GES-24) and also differentiated co-producing carbapenemase strains (KPC and NDM, KPC and OXA, KPC and GES, and NDM and OXA), attributed to its high mass accuracy and simultaneous detection capability. A-MALDI is considered a valuable diagnostic tool for accurately identifying CPE and carbapenemase’s subtypes in clinical isolates. It may also aid in selecting appropriate antibiotics for each carbapenemase subtype. Ultimately, we expect that the A-MALDI method will contribute to preventing the spread of antibiotic resistance and improving human public health.

IMPORTANCE
A-MALDI clearly demonstrated excellent ability to identify CPEs such as KPC, NDM, OXA, and GES when carbapenemase is present in the strain (100% accuracy and precision). The method also successfully discriminated carbapenemase subtypes and simultaneous detection of co-producing multiple carbapenemases in a single strain. This is the first report for simultaneous and multiple detection of intact carbapenemases of KPC, NDM, OXA, and GES using matrix-assisted laser desorption/ionization mass spectrometry in a clinical isolate.
m
6
A demethylase CpALKBH regulates
CpZap1
mRNA stability to modulate the development and virulence of chestnut blight fungus
Authors: Zhao Lijiu , Wei Xiangyu , Chen Fengyue , Chen Baoshan , Li Ru 
Published: November 2024

ABSTRACT

As the most abundant eukaryotic mRNA modification, N
6
-methyladenosine (m
6
A) plays a crucial role in regulating multiple biological processes. This methylation is regulated by methyltransferases and demethylases. However, the regulatory role and mode of action of m
6
A demethylases in fungi remain poorly understood. In this study, we demonstrate that CpALKBH is a demethylase in
Cryphonectria parasitica
that removes m
6
A modification from single-stranded RNA
in vitro
. The deletion of
CpALKBH
resulted in a significant increase in the m
6
A methylation levels, along with decreases in the growth rate, sporulation, and virulence in
C. parasitica
. Additionally, CpZap1—a transcription factor—was identified as a downstream target of CpALKBH demethylase based on RNA sequencing analysis. We confirmed that CpALKBH demethylase regulates
CpZap1
mRNA stability in an m
6
A-dependent manner. Furthermore, through MazF assay, we found that methylation of
CpZap1
at position 1935A is regulated by both CpALKBH demethylase and CpMTA1 methyltransferase.
CpZap1
significantly influences the fungal phenotype and virulence, thereby restoring the abnormal phenotype observed in ∆
CpALKBH
mutants. Collectively, our findings highlight the essential role of CpALKBH as an m
6
A demethylase in the development and virulence of
C. parasitica
, while also elucidating the molecular mechanisms through which m
6
A modification impacts
CpZap1
mRNA stability.

IMPORTANCE

N
6
-methyladenosine (m
6
A) is the most abundant eukaryotic mRNA modification and is involved in various biological processes. Methyltransferases and demethylases regulate the m
6
A modification, but the regulatory role of m
6
A demethylases in fungi remains poorly understood. Here, we demonstrated that CpALKBH functions as a demethylase in
Cryphonectria parasitica
. The deletion of
CpALKBH
leads to a significant increase in m
6
A levels and a reduction in fungal growth, sporulation, and virulence. We identified
CpZap1
as a downstream target of CpALKBH, with CpALKBH regulating
CpZap1
mRNA stability in an m
6
A-dependent manner. Additionally, our findings indicate that methylation at position 1935A of
CpZap1
is regulated by both the CpALKBH demethylase and the CpMTA1 methyltransferase. Given its critical role in fungal development and virulence, overexpression of
CpZap1
can rescue abnormal phenotypes of ∆
CpALKBH
mutant. Overall, these findings contribute to improving our understanding of the role of m
6
A demethylase in fungi.
Naturally occurring influenza reassortment in pigs facilitates the emergence of intrahost virus subpopulations with distinct genotypes and replicative fitness
Authors: Li Chong , Meliopoulos Victoria , Rendahl Aaron , Schultz-Cherry Stacey , Torremorell Montserrat 
Published: November 2024

ABSTRACT

Pigs are recognized as amplifying hosts for influenza A virus (IAV) reassortant viruses. Understanding the extent of IAV reassortment occurring at the individual pig level in naturally infected pigs and how reassortment impacts virus diversity, persistence, and replicative fitness is essential for countering IAV threats to humans and animals. Here, 244 IAV plaques were isolated from 24 commercial pigs, resulting in 26 distinct genome segment constellations. About 33% (8/24) of pigs were infected with two or more different genotypes, with two pigs harboring two or more different subtypes. Our results indicate that few pigs in a population harbor significantly more genotypes than other pigs and generate most of the diversity, including the emergence of reassortants. However, detecting distinct genotypes during surveillance was dynamic, with most of the genotypes subsiding over time. All the IAV genotypes could replicate in various swine and human-sourced respiratory epithelial cells, and we observed that distinct reassortant genotypes recovered from a single pig could exhibit different growth abilities, especially in human cells. Overall, we demonstrated that multiple distinct IAV genotypes with distinct antigenic profiles and varying growth abilities on swine and human respiratory tracts can be shed simultaneously from a single pig, which contributes to the dynamic nature of IAV prevalence. The striking magnitude of IAV reassortment at the single pig level revealed in this study highlights the need to strengthen surveillance efforts and plans to eliminate IAV from swine farms because pigs have a high potential to produce diverse and potentially zoonotic influenza reassortant viruses.

IMPORTANCE
Pigs play a crucial role in driving influenza A virus (IAV) diversification and evolution by reassorting the viruses originating from different hosts. Despite IAV reassortment and diversity being well documented in pig populations at different scales (e.g., farm, region, country), limited field research has explored the extent of reassortment happening at the single pig level and how that contributes to the overall genetic and biological variation observed in populations. We provide initial information on levels of reassortment happening at the single pig level in naturally infected pigs, and that particular pigs can shed a plethora of distinct genotypes, with certain genotypes having distinct replicative fitness on swine and human respiratory tracts, which preserves the potential for IAV long-term evolution and facilitates the emergence of zoonotic/pandemic-capable reassortants.
An exacerbated phosphate starvation response triggers
Mycobacterium tuberculosis
glycerol utilization at acidic pH
Authors: Healy Claire , Ehrt Sabine , Gouzy Alexandre 
Published: November 2024

ABSTRACT

The mechanisms controlling
Mycobacterium tuberculosis
(Mtb) replication and survival inside its human host remain ill-defined. Phagosome acidification and nutrient deprivation are common mechanisms used by macrophages to restrict the replication of intracellular bacteria. Mtb stops replicating at mildly acidic pH (<pH5.8), an adaptive process called “acid growth arrest,” which is thought to play an important role in Mtb virulence. Using a genome-wide mutagenesis screen, we identified 95 genes whose disruption either decreases or increases Mtb fitness during acid growth arrest. We show that the virulence-associated inorganic phosphate (Pi) uptake system (Pst-1) regulates the ability of Mtb to replicate in acidic conditions. Deletion of
pstA1
, a gene coding for a subunit of the Pst-1 system, results in the overexpression of the Pi starvation regulator
regX3,
which is sufficient to restore Mtb growth in acid conditions. Our data further support the role of limited glycerol uptake and ROS-mediated glyceraldehyde-3-phosphate dehydrogenase (GAPDH) inhibition in causing Mtb acid growth arrest. This study reveals an unexpected role of the Pi starvation response in regulating acid growth arrest and highlights the intricacy of the mechanisms regulating redox homeostasis, acid stress response, and nutrient utilization in Mtb.

IMPORTANCE

Despite the availability of antibiotic treatment,
M. tuberculosis
(Mtb), the causative agent of tuberculosis (TB), remains a major infectious disease killer worldwide. A better understanding of the environments that Mtb faces during infection and the mechanisms Mtb employs to respond and adapt may help identify currently unexplored pathways and targets for the development of novel anti-TB drugs. Here, we demonstrate that Mtb growth in acid can be restored by the over-expression of the Pi starvation response regulator
regX3
. This work paves the way toward a better understanding of the mechanisms controlling Mtb growth at acidic pH and highlights the role of inorganic phosphate in this process.
The triterpenoid curcumene mediates the relative hydrophilicity of
Bacillus subtilis
spores
Authors: Castaldi Stefany , Donadio Giuliana , Staiano Ivana , Ricca Ezio , Isticato Rachele 
Published: November 2024

ABSTRACT

Spores of
Bacillus subtilis
are surrounded and protected by the coat and the crust, multi-layered structures mainly made of proteins and polysaccharides. These polysaccharides are covalently linked to some of the coat and crust proteins and influence some spore properties, such as surface adhesion and hydrophilicity. This study reports that a mutant strain lacking the
spsA-L
operon, encoding 11 enzymes involved in the synthesis of spore surface polysaccharides, produced spores exposing on their surface hydrophobic molecules that were responsible for the drastic reduction of hydrophilicity of the mutant spores. Biochemical and genetic data support the identification of the C
35
-terpenoid curcumene, a precursor of the spore-associated lipid sporulene, as the highly hydrophobic molecule present on the surface of mutant spores.

IMPORTANCE
Bacterial spores are the most resistant cell forms on Earth. The metabolically quiescent spores withstand conditions that would be lethal for other cells, maintaining the capacity to sense the environment and respond to the presence of favorable conditions by germinating. Such remarkable resistance is also due to the complex layers that surround the spore cytoplasm and protect it against damaging factors. Altogether, the spore surface layers form a complex cell structure composed of proteins, polysaccharides, and, as highlighted by this study, also of lipids. Understanding the complexity of the spore surface and the specific molecules involved in its structure is an essential step for unraveling the mechanisms underlying the spore’s resistance to environmental assaults.