bluuebunny/crossref_metadata_2025_split huggingface dataset:
A conserved extracellular Ribo1 with broad‐spectrum cytotoxic activity enables smut fungi to compete with host‐associated bacteria
Authors: Ökmen Bilal , Katzy Philipp , Huang Luyao , Wemhöner Raphael , Doehlemann Gunther 
Published: September 2023

Summary

Ribotoxins are secreted ribonucleases that specifically target and cleave the universally conserved sarcin–ricin loop sequence of rRNA, which leads to inhibition of protein biosynthesis and subsequently to cell death. We have identified and characterized a secreted Ribo1 protein of plant pathogenic smut fungi.

Heterologous expression in different model systems showed that smut Ribo1 has cytotoxic activity against bacteria, yeast, host and nonhost plants.

Recombinant expression of Ribo1 in Nicotiana benthamiana induced plant cell death; however, an active site mutant induced cell death only when expressed as a secreted protein. In the maize smut Ustilago maydis, transcription of Ribo1 is specifically induced in early infection stages. While a knockout mutant revealed that Ribo1 is dispensable for U. maydis virulence, the overexpression of Ribo1 in planta had a strong dominant negative effect on virulence and induced host defense responses including cell death.

Our findings suggest a function of Ribo1 during the epiphytic development rather than for invasive colonization of the host. Accordingly, in the presence of the biocontrol bacteria Pantoea sp., which were isolated from maize leaves, the ribo1 knockout mutant was significantly impaired in virulence. Together, we conclude that Ribo1 enables smut fungi to compete with host‐associated bacteria during epiphytic development.
Limits of thermal and hydrological tolerance in a foundation tree species (Populus fremontii) in the desert southwestern United States
Authors: Moran Madeline E. , Aparecido Luiza M. T. , Koepke Dan F. , Cooper Hillary F. , Doughty Christopher E. , Gehring Catherine A. , Throop Heather L. , Whitham Thomas G. , Allan Gerard J. , Hultine Kevin R. 
Published: September 2023

Summary
Populus fremontii is among the most dominant, and ecologically important riparian tree species in the western United States and can thrive in hyper‐arid riparian corridors. Yet, P. fremontii forests have rapidly declined over the last decade, particularly in places where temperatures sometimes exceed 50°C.
We evaluated high temperature tolerance of leaf metabolism, leaf thermoregulation, and leaf hydraulic function in eight P. fremontii populations spanning a 5.3°C mean annual temperature gradient in a well‐watered common garden, and at source locations throughout the lower Colorado River Basin.
Two major results emerged. First, despite having an exceptionally high Tcrit (the temperature at which Photosystem II is disrupted) relative to other tree taxa, recent heat waves exceeded Tcrit, requiring evaporative leaf cooling to maintain leaf‐to‐air thermal safety margins. Second, in midsummer, genotypes from the warmest locations maintained lower midday leaf temperatures, a higher midday stomatal conductance, and maintained turgor pressure at lower water potentials than genotypes from more temperate locations.
Taken together, results suggest that under well‐watered conditions, P. fremontii can regulate leaf temperature below Tcrit along the warm edge of its distribution. Nevertheless, reduced Colorado River flows threaten to lower water tables below levels needed for evaporative cooling during episodic heat waves.
The role of indices in predicting disease severity and outcomes of multisystem inflammatory syndrome in children
Authors: Coşkun Serkan , Güngörer Vildan , Öner Nimet , Sezer Müge , Karagöl Cüneyt , Tekin Zahide Ekici , Tekgöz Pakize Nilüfer , Kaplan Melike Mehveş , Polat Merve Cansu , Çelikel Elif , Acar Banu Çelikel 
Published: September 2023

AbstractBackgroundThe aim of this study was to evaluate the role of the systemic immune inflammation index (SII), C‐reactive protein/albumin ratio (CAR), the monocyte/lymphocyte ratio (MLR), and the neutrophil/lymphocyte ratio (NLR) in predicting disease severity, treatment, and prognosis in multisystem inflammatory syndrome in children (MIS‐C).MethodsThis medical record review retrospectively evaluated the clinical and laboratory findings of 191 MIS‐C patients followed in the Department of Pediatric Rheumatology at Ankara City Hospital, Turkey. The patients were grouped by disease severity: mild, moderate, and severe. SII, CAR, MLR, and NLR were calculated for each group.ResultsAll patients had fever at the time of admission; 153 (80.1%) had gastrointestinal tract involvement, 74 (38.7%) had rash, 63 (33%) had conjunctivitis, 107 (56%) had cardiac involvement, 32 (15.6%) had renal involvement, and 143 (74.9%) had hematological involvement. According to logistic regression analysis, SII, NLR, MLR, and CAR were found to be predictive indexes for disease severity, need for intensive care, need for inotropes, and anakinra treatment in MIS‐C.The cut‐off values of ≥1605.3 for SII, ≥9.1 for NLR, and ≥3.9 for CAR increased the risk of severe disease by 3.4, 7.1, and 5.7 times, respectively.ConclusionNLR, SII, MLR, and CAR are effective and useful for predicting the severity of MIS‐C, the need for intensive care, and the need for anakinra treatment.
Robust condition‐based production and maintenance planning for degradation management
Authors: Sun Qiuzhuang , Chen Piao , Wang Xin , Ye Zhi‐Sheng 
Published: September 2023

We study the robust production and maintenance control for a production system subject to degradation. A periodic maintenance scheme is considered, and the system production rate can be dynamically adjusted before maintenance, serving as a proactive way of degradation management. Optimal control of the degradation rate aims to strike a balance between the risk of failure and the production profit. We first consider the scenario in which the degradation rate increases linearly with the production rate. Different from the existing literature that posits a parametric stochastic degradation process, we suppose that the degradation increment during a period lies in an uncertainty set, and our objective is to minimize the maintenance cost in the worst case. The resulting model is a robust mixed‐integer linear program. We derive its robust counterpart and establish structural properties of the optimal production plan. These properties are then used for real‐time condition‐based control of the production rate through reoptimization. The model is further generalized to the nonlinear production–degradation relation. Based on a real production–degradation dataset from an extruder system, we conduct comprehensive numerical experiments to illustrate the application of the model. Numerical results show that our model significantly outperforms existing methods in terms of the mean and variance of cost rate when degradation model misspecification is presented.
Twenty‐five years of recombinant human growth factors rhPDGF‐BB and rhBMP‐2 in oral hard and soft tissue regeneration
Authors: Galarraga‐Vinueza Maria Elisa , Barootchi Shayan , Nevins Marc L. , Nevins Myron , Miron Richard J. , Tavelli Lorenzo 
Published: September 2023

AbstractContemporary oral tissue engineering strategies involve recombinant human growth factor approaches to stimulate diverse cellular processes including cell differentiation, migration, recruitment, and proliferation at grafted areas. Recombinant human growth factor applications in oral hard and soft tissue regeneration have been progressively researched over the last 25 years. Growth factor‐mediated surgical approaches aim to accelerate healing, tissue reconstruction, and patient recovery. Thus, regenerative approaches involving growth factors such as recombinant human platelet‐derived growth factor‐BB (rhPDGF‐BB) and recombinant human bone morphogenetic proteins (rhBMPs) have shown certain advantages over invasive traditional surgical approaches in severe hard and soft tissue defects. Several clinical studies assessed the outcomes of rhBMP‐2 in diverse clinical applications for implant site development and bone augmentation. Current evidence regarding the clinical benefits of rhBMP‐2 compared to conventional therapies is inconclusive. Nevertheless, it seems that rhBMP‐2 can promote faster wound healing processes and enhance de novo bone formation, which may be particularly favorable in patients with compromised bone healing capacity or limited donor sites. rhPDGF‐BB has been extensively applied for periodontal regenerative procedures and for the treatment of gingival recessions, showing consistent and positive outcomes. Nevertheless, current evidence regarding its benefits at implant and edentulous sites is limited. The present review explores and depicts the current applications, outcomes, and evidence‐based clinical recommendations of rhPDGF‐BB and rhBMPs for oral tissue regeneration.
Long‐term effects of extreme smoke exposure on COVID‐19: A cohort study
Authors: Lane Tyler J. , Carroll Matthew , Borg Brigitte M. , McCaffrey Tracy A. , Smith Catherine L. , Gao Caroline X. , Brown David , Poland David , Allgood Shantelle , Ikin Jillian , Abramson Michael J. 
Published: September 2023

AbstractBackgroundIn 2014, the Hazelwood coalmine fire shrouded the regional Australian town of Morwell in smoke and ash for 6 weeks. One of the fire's by‐products, PM2.5, is associated with an increased risk of COVID‐19 and severe disease. However, it is unclear whether the effect persisted for years after exposure. In this study, we surveyed a cohort established prior to the pandemic to determine whether PM2.5 from the coalmine fire increased long‐term vulnerability to COVID‐19 and severe disease.MethodsFrom August to December 2022, 612 members of the Hazelwood Health Study's adult cohort, established in 2016/17, participated in a follow‐up survey that included standardized items to capture COVID‐19 cases, as well as questions about hospitalization and vaccinations. Associations were evaluated in crude and adjusted logistic regression models.ResultsA total of 268 (44%) participants self‐reported or met symptom criteria for having had COVID‐19 at least once. All models found a positive association, with odds of COVID‐19 increasing by between 4% and 30% for a 10 μg/m3 increase in coalmine fire‐related PM2.5 exposure. However, the association was significant in only 2 of the 18 models. There were insufficient hospitalizations to examine severity (n = 7; 1%).ConclusionThe findings are inconclusive on the effect of coalmine fire‐related PM2.5 exposure on long‐term vulnerability to COVID‐19. Given the positive association that was robust to modelling variations as well as evidence for a causal mechanism, it would be prudent to treat PM2.5 from fire events as a long‐term risk factor until more evidence accumulates.
Anti‐caries Streptococcus spp.: A potential preventive tool for special needs patients
Authors: Mato Eliane García , Montaño‐Barrientos Bitalio J. , Rivas‐Mundiña Berta , Aneiros Iván Varela , López Lucía Sande , Posse Jacobo Limeres , Lamas Lucía Martínez 
Published: September 2023

AbstractIntroductionProbiotics are living microorganisms that act on the host‐microbiome interface to restore the microbiota's physiological homeostasis. Numerous probiotics have been marketed with inhibitory activity against Streptococcus mutans and consequently with a potential anti‐caries effect, mainly of the genera Lactobacillus and Bifidobacterium, whose main disadvantage is their limited ability to settle in the oral cavity.MethodsThis narrative review describes the main Streptococcus spp. with probiotic anti‐Streptococcus mutans activity, whose substantivity is greater than that of Lactobacillus spp. and consequently with anti‐caries potentiality. We performed a literature review in the PubMed, Science Direct and Google Scholar databases of articles published in English (without time restriction) related to caries and probiotics.ResultsThe potential identified anti‐caries probiotics included Streptococcus spp. A12, Streptococcus oralis (AJ3), Streptococcus oligofermentans, Streptococcus salivarius (K12, M18, JH, LAB813, 24SMB), Streptococcus spp. with arginolytic activity (S. sanguinis, S. gordonii, S. ratti, S. parasanguinis, S. intermedius, S. australis, and S. cristatus), Streptococcus rattus (JH145), Streptococcus dentisani and Streptococcus downii.ConclusionsThe possibility of using these Streptococcus spp. as probiotics that inhibit the growth of dental plaque and the development of carious lesions represents a potential tool of particular interest for individuals with physical or intellectual disabilities that impede the routine and effective application of mechanical dental plaque removal techniques.
Mycobacterium tuberculosis
carrying the rifampicin drug-resistance-conferring
rpoB
mutation H445Y is associated with suppressed immunity through type I interferons
Authors: Bobba Suhas , Howard Nicole C. , Das Shibali , Ahmed Mushtaq , Tang Linrui , Thirunavukkarasu Shyamala , Larsen Michelle H. , Mathema Barun , Divangahi Maziar , Khader Shabaana A. 
Published: September 2023

ABSTRACT

Tuberculosis (TB) is one of the leading causes of death due to an infectious disease. The rise of multi-drug resistance (MDR) in
Mycobacterium tuberculosis
(
Mtb
), the causative agent of TB, presents a significant obstacle to TB control. While human studies report dysregulated immune responses during MDR TB, a clear understanding of the host-pathogen interactions of MDR
Mtb
is lacking. Here, we studied the immune responses induced by
Mtb
strains carrying two of the most common rifampicin drug-resistance (RDR)-conferring single-nucleotide polymorphisms (SNPs) in the RNA polymerase gene of
Mtb
, which accounts for nearly 90% of drug-resistance mutations found clinically in
Mtb
. During
Mtb
infection of primary human macrophages, we found that pro-inflammatory cytokine production was reduced upon infection with
Mtb
carrying the H445Y SNP but not the S450L SNP. Using a mouse model, we also characterized the host immune response
in vivo
following infection. Despite similar establishment of
Mtb
infection in the lung and dissemination to the peripheral organs, we show that infection with the RDR
Mtb rpoB
-H445Y strain, but not with the
rpoB
-S450L strain, resulted in a suppressed lung myeloid and lymphoid immune responses through type I IFN-dependent pathways, relative to
wt Mtb
. This suppressed host immunity had functional consequences in limiting control of RDR
Mtb
strains harboring
rpoB
-H445Y and led to worse pathology during chronic TB disease. Collectively, our results suggest that disease pathogenesis may be associated with specific RDR mutations in
Mtb
, which may differentially regulate immune responses.

IMPORTANCE

This study highlights the impact of specific rifampicin-resistance-conferring mutations on the host immune response to
Mycobacterium tuberculosis
(
Mtb
), the causative agent of tuberculosis (TB). Clinical reports have previously suggested that multi-drug-resistant) TB patients exhibit altered peripheral immune responses as compared with their drug-sensitive TB counterparts. The murine model of infection with
Mtb
strains carrying drug-resistance-conferring mutations recapitulated these findings and allowed us to mechanistically interrogate the pathways responsible for driving the divergent immune responses. Our findings underscore the need for greater investigation into bacterial heterogeneity to better appreciate the diversity in host-pathogen interactions during TB disease.
Circulation of enterotoxigenic
Escherichia coli
(ETEC) isolates expressing CS23 from the environment to clinical settings
Authors: Calderon Toledo Carla , von Mentzer Astrid , Agramont Jorge , Thorell Kaisa , Zhou Yingshun , Szabó Miklós , Colque Patricia , Kuhn Inger , Gutiérrez-Cortez Sergio , Joffré Enrique 
Published: September 2023

ABSTRACT

Enterotoxigenic
Escherichia coli
(ETEC) is one of the leading causes of infant diarrhea in low- and middle-income countries (LMICs). Diarrheal pathogens are transmitted through environmental reservoirs; however, the bacterial clones that spread across the human-environment interface remain unexplored. We aimed to determine the relationship and clonal dissemination of ETEC between children with diarrhea and polluted water samples from a local river in La Paz, Bolivia. By using WGS and the PhenePlates phenotypic system to analyze ETEC strains, we showed that ST218 and ST410 LT+STh ETEC expressing the colonization factor (CF) CS23 were found with high frequency in both samples. The CS23 ETEC isolates were found within several STs,
E. coli
phylogroups, and across ETEC lineages. Comparative genomic evaluation and PhenePlate screening of globally distributed clinical ETEC strains suggest that the CS23 gene is likely carried on plasmids acquired independently of the bacterial chromosomal background. Clinical strains were more often multidrug-resistant (MDR) than environmental isolates and harbored the class 1 integron-integrase gene
intI1
next to the MDR cassettes. Retrospective analysis of antibiotic resistance in ETEC revealed a high frequency of MDR in clinical isolates. The LT+STh CS23 environmental ETEC isolates, showed an increased biofilm ability at environmental temperature, equal cytotoxicity, and significantly lower adherence to human epithelial cells compared to ETEC expressing other CFs. Together, we suggest that CS23 is more prevalent in ETEC than previously estimated, and the Choqueyapu River is a reservoir for LT+STh CS23 ETEC containing strains capable of causing diarrheal cases in children.

IMPORTANCE

The importance of clean water cannot be overstated. It is a vital resource for maintaining health and well-being. Unfortunately, water sources contaminated with fecal discharges from animal and human origin due to a lack of wastewater management pose a significant risk to communities, as they can become a means of transmission of pathogenic bacteria like enterotoxigenic
E. coli
(ETEC). ETEC is frequently found in polluted water in countries with a high prevalence of diarrheal diseases, such as Bolivia. This study provides novel insights into the circulation of ETEC between diarrheal cases and polluted water sources in areas with high rates of diarrheal disease. These findings highlight the Choqueyapu River as a potential reservoir for emerging pathogens carrying antibiotic-resistance genes, making it a crucial area for monitoring and intervention. Furthermore, the results demonstrate the feasibility of a low-cost, high-throughput method for tracking bacterial pathogens in low- and middle-income countries, making it a valuable tool for One Health monitoring efforts.
Functional characterization of genes encoding cadmium pumping P
1B
-type ATPases in
Aspergillus fumigatus
and
Aspergillus nidulans
Authors: Vig Ildikó , Benkő Zsigmond , Gila Barnabás Cs. , Palczert Zoltán , Jakab Ágnes , Nagy Fruzsina , Miskei Márton , Lee Mi-Kyung , Yu Jae-Hyuk , Pócsi István , Emri Tamás 
Published: September 2023

ABSTRACT

Several P
1B
-type ATPases are important Cd
2+
/Cu
2+
pumps in
Aspergillus
species, and they are tightly associated with the heavy metal stress tolerance of these ascomycetous fungi. To better understand the roles of the two P
1B
-type ATPases,
Aspergillus nidulans
CrpA Cd
2+
/Cu
2+
pump (orthologue of the
Candida albicans Crp1
Cd
2+
/Cu
2+
pump) and
Aspergillus fumigatus
PcaA Cd
2+
pump (orthologue of the
Saccharomyces cerevisiae
Pca1 Cd
2+
pump), we have generated individual mutants and characterized their heavy metal susceptibilities. The deletion of CrpA in
A. nidulans
has led to the increased sensitivity of the fungus to stresses induced by Zn
2+
, Fe
2+
, or the combination of oxidative-stress-inducing menadione sodium bisulfite and Fe
3+
. Heterologous expression of
A. fumigatus
PcaA in the
S. cerevisiae pca1
deletion mutant has resulted in enhanced tolerance of the yeast to stresses elicited by Cd
2+
or Zn
2+
but not by Fe
2+
/Fe
3+
or Cu
2+
. Mammalian host immune defense can attack microbes by secreting Zn
2+
or Cu
2+
, and the oxidative stress induced by host immune systems can also disturb metal (Cu
2+
, Fe
2+
, and Zn
2+
) homeostasis in microbes. In summary, PcaA and CrpA can protect fungal cells from these complex stresses that contribute to the virulence of the pathogenic
Aspergillus
species. Moreover, due to their presence on the fungal cell surface, these P
1B
-type ATPases may serve as a novel drug target in the future.

IMPORTANCE

Mammalian host immune defense disrupts heavy metal homeostasis of fungal pathogens. P1B-type ATPase of
Aspergillus fumigatus
and
Aspergillus nidulans
may help to cope with this stress and serve as virulence traits. In our experiments, both
A. nidulans
Cd2+/Cu2+ pump CrpA and
A. fumigatus
Cd2+ pump PcaA protected fungal cells from toxic Zn2+, and CrpA also decreased Fe2+ susceptibility most likely indirectly. In addition, CrpA protected cells against the combined stress induced by the oxidative stressor menadione and Fe3+. Since P1B-type ATPases are present on the fungal cell surface, these proteins may serve as a novel drug target in the future.
DegQ is an important policing link between quorum sensing and regulated adaptative traits in
Bacillus subtilis
Authors: Danevčič Tjaša , Spacapan Mihael , Dragoš Anna , Kovács Ákos T. , Mandic-Mulec Ines 
Published: September 2023

ABSTRACT

Quorum sensing (QS) is a widespread bacterial communication system that controls important adaptive traits in a cell density-dependent manner. However, mechanisms by which QS-regulated traits are linked within the cell and mechanisms by which these links affect adaptation are not well understood. In this study,
Bacillus subtilis
was used as a model bacterium to investigate the link between the ComQXPA QS system, DegQ, surfactin and protease production in planktonic and biofilm cultures. The work tests two alternative hypotheses predicting that hypersensitivity of the QS signal-deficient mutant (
comQ::kan
) to exogenously added ComX, resulting in increased surfactin production, is linked to an additional genetic locus, or alternatively, to overexpression of the ComX receptor ComP. Results are in agreement with the first hypothesis and show that the P

srfAA

hypersensitivity of the
comQ::kan
mutant is linked to a 168 strain-specific mutation in the P

degQ

region. Hence, the markerless Δ
comQ
mutant lacking this mutation is not overresponsive to ComX. Such hyper-responsiveness is specific for the P

srfAA

and not detected in another ComX-regulated promoter, the P

aprE

, which is under the positive control by DegQ. Our results suggest that DegQ by exerting differential effect on P

srfAA

and P

aprE

acts as a policing mechanism and the intracellular link, which guards the cell from an overinvestment into surfactin production.

IMPORTANCE
DegQ levels are known to regulate surfactin synthesis and extracellular protease production, and DegQ is under the control of the ComX-dependent QS. DegQ also serves as an important policing link between these QS-regulated processes, preventing overinvestment in these costly processes. This work highlights the importance of DegQ, which acts as the intracellular link between ComX production and the response by regulating extracellular degradative enzyme synthesis and surfactin production.