bluuebunny/crossref_metadata_2025_split huggingface dataset:
An NADH/NAD
+
-favored aldo-keto reductase facilitates avilamycin A biosynthesis by primarily catalyzing oxidation of avilamycin C
Authors: Zhang Derundong , Wang Yaotong , Tang Qunyan , Zhang Qinglin , Ji Xiaowei , Qiu Xiangqi , Chen Dandan , Liu Wen 
Published: March 2024

ABSTRACT

Avilamycins, which possess potent inhibitory activity against Gram-positive bacteria, are a group of oligosaccharide antibiotics produced by
Streptomyces viridochromogenes
. Among these structurally related oligosaccharide antibiotics, avilamycin
A
serves as the main bioactive component in veterinary drugs and animal feed additives, which differs from avilamycin
C
only in the redox state of the two-carbon branched-chain of the terminal octose moiety. However, the mechanisms underlying assembly and modification of the oligosaccharide chain to diversify individual avilamycins remain poorly understood. Here, we report that AviZ1, an aldo-keto reductase in the avilamycin pathway, can catalyze the redox conversion between avilamycins
A
and
C
. Remarkably, the ratio of these two components produced by AviZ1 depends on the utilization of specific redox cofactors, namely NADH/NAD
+
or NADPH/NADP
+
. These findings are inspired by gene disruption and complementation experiments and are further supported by
in vitro
enzymatic activity assays, kinetic analyses, and cofactor affinity studies on AviZ1-catalyzed redox reactions. Additionally, the results from sequence analysis, structure prediction, and site-directed mutagenesis of AviZ1 validate it as an NADH/NAD
+
-favored aldo-keto reductase that primarily oxidizes avilamycin
C
to form avilamycin
A
by utilizing abundant NAD
+
in vivo
. Building upon the biological function and catalytic activity of AviZ1, overexpressing AviZ1 in
S. viridochromogenes
is thus effective to improve the yield and proportion of avilamycin
A
in the fermentation profile of avilamycins. This study represents, to our knowledge, the first characterization of biochemical reactions involved in avilamycin biosynthesis and contributes to the construction of high-performance strains with industrial value.

IMPORTANCE

Avilamycins are a group of oligosaccharide antibiotics produced by
Streptomyces viridochromogenes
, which can be used as veterinary drugs and animal feed additives. Avilamycin
A
is the most bioactive component, differing from avilamycin
C
only in the redox state of the two-carbon branched-chain of the terminal octose moiety. Currently, the biosynthetic pathway of avilamycins is not clear. Here, we report that AviZ1, an aldo-keto reductase in the avilamycin pathway, can catalyze the redox conversion between avilamycins
A
and
C
. More importantly, AviZ1 exhibits a unique NADH/NAD
+
preference, allowing it to efficiently catalyze the oxidation of avilamycin
C
to form avilamycin
A
using abundant NAD
+
in cells. Thus, overexpressing AviZ1 in
S. viridochromogenes
is effective to improve the yield and proportion of avilamycin
A
in the fermentation profile of avilamycins. This study serves as an enzymological guide for rational strain design, and the resulting high-performance strains have significant industrial value.
Sulfate-reducing bacteria unearthed: ecological functions of the diverse prokaryotic group in terrestrial environments
Authors: Demin Konstantin A. , Prazdnova Evgeniya V. , Minkina Tatiana M. , Gorovtsov Andrey V. 
Published: March 2024

ABSTRACT

Sulfate-reducing prokaryotes (SRPs) are essential microorganisms that play crucial roles in various ecological processes. Even though SRPs have been studied for over a century, there are still gaps in our understanding of their biology. In the past two decades, a significant amount of data on SRP ecology has been accumulated. This review aims to consolidate that information, focusing on SRPs in soils, their relation to the rare biosphere, uncultured sulfate reducers, and their interactions with other organisms in terrestrial ecosystems. SRPs in soils form part of the rare biosphere and contribute to various processes as a low-density population. The data reveal a diverse range of sulfate-reducing taxa intricately involved in terrestrial carbon and sulfur cycles. While some taxa like
Desulfitobacterium
and
Desulfosporosinus
are well studied, others are more enigmatic. For example, members of the Acidobacteriota phylum appear to hold significant importance for the terrestrial sulfur cycle. Many aspects of SRP ecology remain mysterious, including sulfate reduction in different bacterial phyla, interactions with bacteria and fungi in soils, and the existence of soil sulfate-reducing archaea. Utilizing metagenomic, metatranscriptomic, and culture-dependent approaches will help uncover the diversity, functional potential, and adaptations of SRPs in the global environment.
Long-duration environmental biosensing by recording analyte detection in DNA using recombinase memory
Authors: Kalvapalle Prashant Bharadwaj , Sridhar Swetha , Silberg Jonathan J. , Stadler Lauren B. 
Published: March 2024

ABSTRACT

Microbial biosensors that convert environmental information into real-time visual outputs are limited in their sensing abilities in complex environments, such as soil and wastewater, due to optical inaccessibility. Biosensors that could record transient exposure to analytes within a large time window for later retrieval represent a promising approach to solve the accessibility problem. Here, we test the performance of recombinase-memory biosensors that sense a sugar (arabinose) and a microbial communication molecule (3-oxo-C12-L-homoserine lactone) over 8 days (~70 generations) following analyte exposure. These biosensors sense the analyte and trigger the expression of a recombinase enzyme which flips a segment of DNA, creating a genetic memory, and initiates fluorescent protein expression. The initial designs failed over time due to unintended DNA flipping in the absence of the analyte and loss of the flipped state after exposure to the analyte. Biosensor performance was improved by decreasing recombinase expression, removing the fluorescent protein output, and using quantitative PCR to read out stored information. Application of memory biosensors in wastewater isolates achieved memory of analyte exposure in an uncharacterized
Pseudomonas
isolate. By returning these engineered isolates to their native environments, recombinase-memory systems are expected to enable longer duration and
in situ
investigation of microbial signaling, cross-feeding, community shifts, and gene transfer beyond the reach of traditional environmental biosensors.

IMPORTANCE

Microbes mediate ecological processes over timescales that can far exceed the half-lives of transient metabolites and signals that drive their collective behaviors. We investigated strategies for engineering microbes to stably record their transient exposure to a chemical over many generations through DNA rearrangements. We identify genetic architectures that improve memory biosensor performance and characterize these in wastewater isolates. Memory biosensors are expected to be useful for monitoring cell-cell signals in biofilms, detecting transient exposure to chemical pollutants, and observing microbial cross-feeding through short-lived metabolites within cryptic methane, nitrogen, and sulfur cycling processes. They will also enable
in situ
studies of microbial responses to ephemeral environmental changes, or other ecological processes that are currently challenging to monitor non-destructively using real-time biosensors and analytical instruments.
Alternate routes to mnm
5
s
2
U synthesis in Gram-positive bacteria
Authors: Jaroch Marshall , Sun Guangxin , Tsui Ho-Ching Tiffany , Reed Colbie , Sun Jingjing , Jörg Marko , Winkler Malcolm E. , Rice Kelly C. , Dziergowska Agnieszka , Stich Troy A. , Dedon Peter C. , Dos Santos Patricia C. , de Crécy-Lagard Valérie 
Published: March 2024

ABSTRACT

The wobble bases of tRNAs that decode split codons are often heavily modified. In bacteria, tRNA
Glu, Gln, Asp
contains a variety of xnm
5
s
2
U derivatives. The synthesis pathway for these modifications is complex and fully elucidated only in a handful of organisms, including the Gram-negative
Escherichia coli
K12 model. Despite the ubiquitous presence of mnm
5
s
2
U modification, genomic analysis shows the absence of
mnmC
orthologous genes, suggesting the occurrence of alternate biosynthetic schemes for the conversion of cmnm
5
s
2
U to mnm
5
s
2
U. Using a combination of comparative genomics and genetic studies, a member of the YtqA subgroup of the radical Sam superfamily was found to be involved in the synthesis of mnm
5
s
2
U in both
Bacillus subtilis
and
Streptococcus mutans
. This protein, renamed MnmL, is encoded in an operon with the recently discovered MnmM methylase involved in the methylation of the pathway intermediate nm
5
s
2
U into mnm
5
s
2
U in
B. subtilis
. Analysis of tRNA modifications of both
S. mutans
and
Streptococcus pneumoniae
shows that growth conditions and genetic backgrounds influence the ratios of pathway intermediates owing to regulatory loops that are not yet understood. The MnmLM pathway is widespread along the bacterial tree, with some phyla, such as Bacilli, relying exclusively on these two enzymes. Although mechanistic details of these newly discovered components are not fully resolved, the occurrence of fusion proteins, alternate arrangements of biosynthetic components, and loss of biosynthetic branches provide examples of biosynthetic diversity to retain a conserved tRNA modification in Nature.

IMPORTANCE

The xnm
5
s
2
U modifications found in several tRNAs at the wobble base position are widespread in bacteria where they have an important role in decoding efficiency and accuracy. This work identifies a novel enzyme (MnmL) that is a member of a subgroup of the very versatile radical SAM superfamily and is involved in the synthesis of mnm
5
s
2
U in several Gram-positive bacteria, including human pathogens. This is another novel example of a non-orthologous displacement in the field of tRNA modification synthesis, showing how different solutions evolve to retain U34 tRNA modifications.
Hepatitis E virus ORF3 protein hijacking thioredoxin domain-containing protein 5 (TXNDC5) for its stability to promote viral particle release
Authors: Sheng Yamin , Deng Yingying , Li Xiaoxuan , Ji Pinpin , Sun Xuwen , Liu Baoyuan , Zhu Jiahong , Zhao Jiakai , Nan Yuchen , Zhou En-Min , Hiscox Julian A. , Stewart James P. , Sun Yani , Zhao Qin 
Published: March 2024

ABSTRACT

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide, responsible for approximately 20 million infections annually. Among the three open reading frames (ORFs) of the HEV genome, the ORF3 protein is involved in virus release. However, the host proteins involved in HEV release need to be clarified. In this study, a host protein, thioredoxin domain-containing protein 5 (TXNDC5), interacted with the non-palmitoylated ORF3 protein by co-immunoprecipitation analysis. We determined that the overexpression or knockdown of TXNDC5 positively regulated HEV release from the host cells. The
17
FCL
19
mutation of the ORF3 protein lost the ability to interact with TXNDC5. The releasing amounts of HEV with the ORF3 mutation (FCL17-19SSP) were decreased compared with wild-type HEV. The overexpression of TXNDC5 can stabilize and increase ORF3 protein amounts, but not the TXNDC5 mutant with amino acids 1–88 deletion. Meanwhile, we determined that the function of TXNDC5 on the stabilization of ORF3 protein is independent of the Trx-like domains. Knockdown of TXNDC5 could lead to the degradation of ORF3 protein by the endoplasmic reticulum (ER)-associated protein degradation-proteasome system. However, the ORF3 protein cannot be degraded in the knockout-TXNDC5 stable cells, suggesting that it may hijack other proteins for its stabilization. Subsequently, we found that the other members of protein disulfide isomerase (PDI), including PDIA1, PDIA3, PDIA4, and PDIA6, can increase ORF3 protein amounts, and PDIA3 and PDIA6 interact with ORF3 protein. Collectively, our study suggested that HEV ORF3 protein can utilize TXNDC5 for its stability in ER to facilitate viral release.

IMPORTANCE
Hepatitis E virus (HEV) infection is the leading cause of acute viral hepatitis worldwide. After the synthesis and modification in the cells, the mature ORF3 protein is essential for HEV release. However, the host protein involved in this process has yet to be determined. Here, we reported a novel host protein, thioredoxin domain-containing protein 5 (TXNDC5), as a chaperone, contributing to HEV release by facilitating ORF3 protein stability in the endoplasmic reticulum through interacting with non-palmitoylated ORF3 protein. However, we also found that in the knockout-TXNDC5 stable cell lines, the HEV ORF3 protein may hijack other proteins for its stabilization. For the first time, our study demonstrated the involvement of TXNDC5 in viral particle release. These findings provide some new insights into the process of the HEV life cycle, the interaction between HEV and host factors, and a new direction for antiviral design.
Ten promotion and tenure tips for microbiologists and immunologists
Authors: Yount Jacob S. 
Published: March 2024

ABSTRACT

In this editorial, I share advice and general principles based on recent experiences as a mentor and evaluator for early-career microbiology and immunology faculty seeking promotion and tenure. I outline 10 recommendations covering research, service, teaching, and mentoring. In addition, I encourage nuanced conversations with colleagues to strategically navigate the unique promotion and tenure processes at different institutions. I hope that these practical tips will assist early-career faculty in attaining promotion and tenure, contributing to long-term scientific and career advances.
Analysis of justification for author order and gender bias in author order among those contributing equally
Authors: Mattoon Ellie Rose , Miles Maisha , Broderick Nichole A. , Casadevall Arturo 
Published: March 2024

ABSTRACT

The practice of designating two or more authors as equal contributors (ECs) on a scientific publication is increasingly common as a form of sharing credit. However, EC authors are often unclearly attributed on curriculum vitae (CVs) or citation engines, and it is unclear how research teams determine author order within an EC listing. In response to studies showing that male authors were more likely to be placed first in an EC listing, the American Society for Microbiology (ASM) required that authors explain the reasons for author order beginning in 2020. In this study, we analyze data from over 2,500 ASM publications to see how this policy affected gender bias and how research teams are making decisions on author order. Data on publications from 2018 to 2021 show that gender bias was largely nonsignificant both before and after authors were asked by ASM to provide an EC statement. The most likely reasons for EC order included alphabetical order, seniority, and chance, although there were differences for publications from different geographic regions. However, many research teams used unique methods in order selection, highlighting the importance of EC statements to provide clarity for readers, funding agencies, and tenure committees.

IMPORTANCE

First-author publications are important for early career scientists to secure funding and educational opportunities. However, an analysis published in
eLife
in 2019 noted that female authors are more likely to be placed second even when both authors report they have contributed equally. American Society for Microbiology announced in response that they would require submissions to include a written justification of author order. In this paper, we analyze the resultant data and show that laboratories are most likely to use some combination of alphabetical order, seniority, and chance to determine author order. However, the prevalence of these methods varies based on the research team's geographic location. These findings highlight the importance of equal contributor statements to provide clarity for readers, funding agencies, and tenure committees. Furthermore, this work is critically important for understanding how these decisions are made and provides a glimpse of the sociology of science.
Guidance on sexual, reproductive, maternal, newborn, child and adolescent health in humanitarian and fragile settings: a scoping review
Authors: Shah Mehr Gul , Dey Teesta , Kostelecky Sophie Marie , El Bizri Maria , Rodo Mariana , Singh Neha S , Aboubaker Samira , Evers Egmond Samir , Ashorn Per , Langlois Etienne V 
Published: March 2024

IntroductionProgress related to sexual, reproductive, maternal, newborn, child and adolescent health (SRMNCAH) has stalled. COVID-19, conflict and climate change threaten to reverse decades of progress and to ensure the health and well-being of vulnerable populations in humanitarian and fragile settings (HFS) going forward, there is a need for tailored guidance for women, children and adolescents (WCA). This review seeks to map and appraise current resources on SRMNCAH in HFS.MethodsIn line with the updated Joanna Briggs Institute guidance and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews framework, a manual literature review was conducted of global and regional guidance published between January 2008 and May 2023 from members of the Global Health Cluster, the Global Nutrition Cluster and the Inter-Agency Working Group on Reproductive Health in Crises. A content analysis was conducted. Scores were then calculated according to the Appraisal of Guidelines for Research and Evaluation II scoring tool and subsequently categorised as high quality or low quality.ResultsA total of 730 documents were identified. Of these, 141 met the selection criteria and were analysed. Available guidance for delivering SRMNCH services exists, which can inform policy and programming for the general population and WCA. Important gaps related to beneficiaries, health services and health system strengthening strategies were identified.ConclusionThe review revealed there is evidence-based guidance available to support interventions targeting WCA in HFS, including: pregnant and lactating women, women of reproductive age, adolescents, newborns, small vulnerable newborns, stillbirths, refugees and internally displaced persons and WCA with disabilities. However, gaps related to beneficiaries, health services and health system strengthening strategies must be addressed in updated guidance that is created, disseminated and monitored in a standardised way that is mindful of the need to respond rapidly in HFS.
Antenatal care services in Benin and Tanzania 2021/2022: an equity analysis study
Authors: Ochieng Walter , Munsey Anna , Kinyina Alen , Assenga Melkior , Onikpo Faustin , Binazon Alexandre , Adeyemi Marie , Alao Manzidatou , Aron Sijenunu , Nhiga Samwel , Niemczura Julie , Buekens Julie , Kitojo Chong , Reaves Erik , Husseini Ahmed Saadani , Drake Mary , Wolf Katherine , Suhowatsky Stephanie , Hounto Aurore , Lemwayi Ruth , Gutman Julie 
Published: March 2024

IntroductionAntenatal care (ANC) interventions improve maternal and neonatal outcomes. However, access to ANC may be inequitable due to sociocultural, monetary and time factors. Examining drivers of ANC disparities may identify those amenable to policy change.MethodsWe conducted an ANC services equity analysis in selected public facilities in Geita, Tanzania, where most services are free to the end-user, and Atlantique, Benin, where every visit incurs user fees. Data on total ANC contacts, quality of care (QoC) indicators and wait times were collected from representative household surveys in the catchment of 40 clinics per country and were analysed by education and wealth. We used indices of inequality, concentration indices and Oaxaca-Blinder decompositions to determine the distribution, direction and magnitude of inequalities and their contributing factors. We assessed out-of-pocket expenses and the benefit incidence of government funding.ResultsANC clients in both countries received less than the recommended minimum ANC contacts: 3.41 (95% CI 3.36 to 3.41) in Atlantique and 3.33 (95% CI 3.27 to 3.39) in Geita. Wealthier individuals had more ANC contacts than poorer ones at every education level in both countries; the wealthiest and most educated had two visits more than the poorest, least educated. In Atlantique, ANC attendees receive similar QoC regardless of socioeconomic status. In Geita, there are wide disparities in QoC received by education or wealth. In Atlantique, out-of-pocket expenses for the lowest wealth quintile are 2.7% of annual income compared with 0.8% for the highest, with user fees being the primary expense. In Geita, the values are 3.1% and 0.5%, respectively; transportation is the main expense.ConclusionsInequalities in total ANC visits favouring wealthier, more educated individuals were apparent in both countries. In Atlantique, reduction of user-fees could improve ANC access. In Geita, training and equipping healthcare staff could improve QoC. Community health services could mitigate access barriers.
Physical activity, physical fitness and self-rated health: cross-sectional and longitudinal associations in adolescents
Authors: Joensuu Laura , Tammelin Tuija H , Syväoja Heidi J , Barker Alan R , Parkkari Jari , Kujala Urho M 
Published: March 2024

ObjectivesTo evaluate the independent associations of physical activity and physical fitness with self-rated health in adolescents.MethodsData from a 2-year observational study (2013–2015) were used (n=256, 58% girls, 13.7±0.3 years at baseline). Self-rated health was assessed with a questionnaire, physical activity by an accelerometer and a questionnaire, and physical fitness via the measurements included in the Finnish national Move! monitoring system for physical functional capacity and their z-score average (fitness index).ResultsSelf-reported physical activity had cross-sectional associations with self-rated health (girls β 0.213, p=0.006, β 0.221 boys p=0.021) while accelerometer-based moderate-to-vigorous physical activity did not. Higher self-reported physical activity at baseline was associated with higher self-rated health at follow-up in boys (β 0.289, p<0.001), but not in girls (β −0.056, p=0.430). Accelerometer-based moderate-to-vigorous physical activity had positive longitudinal associations with future self-rated health in boys, but some of these similar associations were negative in girls. Fitness index had a positive cross-sectional association with self-rated health in boys (β 0.282 or β 0.283, p=0.002), but not in girls (β 0.162 or β 0.161, p=0.051). Physical fitness was not longitudinally associated with self-rated health.ConclusionsSelf-reported physical activity showed potential to explain current and future self-rated health better than accelerometer-based physical activity or physical fitness. We recommended to consider self-reported physical activity as an adequate metric of adolescent health in the population-level surveillance systems.