bluuebunny/crossref_metadata_2025 huggingface dataset:
Systemic histone deacetylase inhibition ameliorates the aberrant responses to acute stress in socially isolated male mice
Authors: Hernandez Carballo Luis Gustavo , Li Pei , Senek Rachel , Yan Zhen
Published: March 2024

Adverse experiences in early life can induce maladaptive responses to acute stress in later life. Chronic social isolation during adolescence is an early life adversity that can precipitate stress‐related psychiatric disorders. We found that male mice after 8 weeks of adolescent social isolation (SI) have markedly increased aggression after being exposed to 2 h of restraint stress (RS), which was accompanied by a significant increase of AMPA receptor‐ and NMDA receptor‐mediated synaptic transmission in prefrontal cortex (PFC) pyramidal neurons of SIRS males. Compared to group‐housed counterparts, SIRS males exhibited a significantly decreased level of histone H3 acetylation in PFC. Systemic administration of class I histone deacetylase inhibitors, romidepsin or MS‐275, ameliorated the aggressive behaviour, as well as general social interaction deficits, of SIRS males. Electrophysiological recordings also found normalization of PFC glutamatergic currents by romidepsin treatment of SIRS male mice. These results revealed an epigenetic mechanism and intervention avenue for aggression induced by chronic social isolation.

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Key points

Adolescent chronic social isolation can precipitate stress‐related psychiatric disorders.

A significant increase of glutamatergic transmission is found in the prefrontal cortex (PFC) of socially isolated male mice exposed to an acute stress (SIRS).

Treatment with class I histone deacetylase (HDAC) inhibitors ameliorates the aggressive behaviour and social interaction deficits of SIRS males, and normalizes glutamatergic currents in PFC neurons.

It provides an epigenetic mechanism and intervention avenue for aberrant stress responses induced by chronic social isolation.
Using Multiscale Atmospheric Modeling to Explore the Impact of Surface Albedo on Anthropogenic Heat Release
Authors: Dey Shuv , Mallen Evan , Stone Brian , Joshi Yogendra
Published: March 2024

Cities account for over 66% of global energy use and with over 68% of the population expected to live in urbanized areas by 2050, anthropogenic urban heat release is likely to become one of the most significant contributors to the creation of urban microclimates. In the present work, an open-source framework for one-way upstream coupled multiscale urban thermal environment simulations is examined and validated and can provide valuable insights about the flow behavior and energy transport between spatial scales. In this study, a city-wide multiscale model with over 500,000 building, road, and tree canopy data points parameterizing Atlanta, GA as a digital twin is developed and validated with a spatial scale of 5 m. The validated model is used to perform a parametric study on the implications bulk surface albedo (SA) has on the city's anthropogenic heat (AH) release in terms of heat flux. The study demonstrates that anthropogenic heat flux for building waste energy accounts for a small part of the total surface heat flux, and a detailed understanding of the components of urban heat (particularly with respect to total surface heat flux) is required to predict and simulate an urban thermal environment.
Time-Resolved Local Loss Analysis of Single- and Two-Blade Pump Flow
Authors: Pesch Andreas , Skoda Romuald
Published: March 2024

A method for the evaluation of time-resolved entropy production in isothermal and incompressible flow is presented. It is applied as a postprocessing of the three-dimensional (3D) flow field obtained by time-resolved computational fluid dynamics (CFD) with scale adaptive turbulence modeling. Wall functions for direct and turbulent entropy production are presented for a cell-centered finite volume method, implemented in the open-source software OpenFOAM and validated on channel, asymmetric diffuser, and periodic hill flow. Single- and two-blade centrifugal pump flow is considered for a wide range of load conditions. Results are compared to experimental data. Time-averaged analysis shows essentially the same loss density distribution among pump components for both pumps, with the impeller and volute region contributing the most, especially in off-design conditions. For both pumps, the losses exhibit significant fluctuations due to impeller–volute interactions. The fluctuation magnitude of loss density is in the same range as flowrate fluctuations and much smaller than pressure fluctuation magnitude. For the two-blade pump (2BP), loss fluctuation magnitude is smaller than for the single-blade pump (1BP). Distinct loss mechanisms are identified for different load conditions. Upon blade passage, a promoted or attenuated volute tongue separation is imposed at part or overload, respectively. In between blade passages, a direct connection from pump inlet to the discharge leads to enhanced flowrate and loss density fluctuations. Future work aims at extending this analysis to stronger off-design conditions in multiblade pumps, where stochastic cycle fluctuations occur.
Investigating the Relevance of Maximal Speed and Acceleration in Varsity-Level Female Ice Hockey Players
Authors: Gamble Alexander S.D. , Thompson Kyle M.A. , Bigg Jessica L. , Pignanelli Christopher , Spriet Lawrence L. , Burr Jamie F.
Published: March 2024

Purpose: To characterize and compare female ice hockey players’ peak skating speed and acceleration ability during linear sprints and gameplay. We also sought to quantify the time spent at various speeds and the frequency of accelerations at different thresholds during games. Methods: Seventeen varsity-level female ice hockey players (20 [1.4] y, 68.9 [4.9] kg, 167.6 [4.7] cm) participated in an on-ice practice session (performing 3 × 40-m linear sprints) and 4 regular-season games while being monitored using a local positioning system. Speed and acceleration were recorded from the sprint and within-game monitoring. Time on ice spent in relative skating speed zones and the frequency of accelerations at different intensities were recorded. Results: Players’ greatest peak speeds (29.5 [1.3] vs 28.3 [1.1] km/h) and accelerations (4.39 [0.48] vs 3.34 [0.36] m/s2) reached during gameplay were higher than those reached in linear sprinting (both P < .01). Peak in-game values were moderately predicted by linear sprint values for speed (r = .69, P < .01) but not for acceleration (r < .01, P = .95). Players spent little time at near-peak linear sprint speeds (≥80% [22.7 km/h], ∼3% time on ice; ≥90% [25.5 km/h], <1% of time on ice) during gameplay. However, 26% to 35% of accelerations recorded during the 4 games were ≥90% of linear sprint acceleration. Conclusions: Although skating speed may be advantageous in specific game situations, our results suggest that players spend little time at near-maximal speeds while accelerating frequently during games. This warrants further investigation of direction changes, skating transitions, repeated sprints, and other determinant variables potentially related to on-ice success and the implementation of training strategies to improve repeated acceleration or qualities beyond maximal skating speed.
Exercise-induced BDNF promotes PPARδ-dependent reprogramming of lipid metabolism in skeletal muscle during exercise recovery
Authors: Chan Wing Suen , Ng Chun Fai , Pang Brian Pak Shing , Hang Miaojia , Tse Margaret Chui Ling , Iu Elsie Chit Yu , Ooi Xin Ci , Yang Xiuying , Kim Jason K. , Lee Chi Wai , Chan Chi Bun
Published: March 2024

Post-exercise recovery is essential to resolve metabolic perturbations and promote long-term cellular remodeling in response to exercise. Here, we report that muscle-generated brain-derived neurotrophic factor (BDNF) elicits post-exercise recovery and metabolic reprogramming in skeletal muscle. BDNF increased the post-exercise expression of the gene encoding PPARδ (peroxisome proliferator–activated receptor δ), a transcription factor that is a master regulator of lipid metabolism. After exercise, mice with muscle-specific
Bdnf
knockout (
MBKO
) exhibited impairments in PPARδ-regulated metabolic gene expression, decreased intramuscular lipid content, reduced β-oxidation, and dysregulated mitochondrial dynamics. Moreover,
MBKO
mice required a longer period to recover from a bout of exercise and did not show increases in exercise-induced endurance capacity. Feeding naïve mice with the bioavailable BDNF mimetic 7,8-dihydroxyflavone resulted in effects that mimicked exercise-induced adaptations, including improved exercise capacity. Together, our findings reveal that BDNF is an essential myokine for exercise-induced metabolic recovery and remodeling in skeletal muscle.
Use of multiple pharmacodynamic measures to deconstruct the Nix-TB regimen in a short-course murine model of tuberculosis
Authors: Lyons M. A. , Obregon-Henao A. , Ramey M. E. , Bauman A. A. , Pauly S. , Rossmassler K. , Reid J. , Karger B. , Walter N. D. , Robertson G. T.
Published: March 2024

A major challenge for tuberculosis (TB) drug development is to prioritize promising combination regimens from a large and growing number of possibilities. This includes demonstrating individual drug contributions to the activity of higher-order combinations. A BALB/c mouse TB infection model was used to evaluate the contributions of each drug and pairwise combination in the clinically relevant Nix-TB regimen [bedaquiline-pretomanid-linezolid (BPaL)] during the first 3 weeks of treatment at human equivalent doses. The rRNA synthesis (RS) ratio, an exploratory pharmacodynamic (PD) marker of ongoing
Mycobacterium tuberculosis
rRNA synthesis, together with solid culture CFU counts and liquid culture time to positivity (TTP) were used as PD markers of treatment response in lung tissue; and their time-course profiles were mathematically modeled using rate equations with pharmacologically interpretable parameters. Antimicrobial interactions were quantified using Bliss independence and Isserlis formulas. Subadditive (or antagonistic) and additive effects on bacillary load, assessed by CFU and TTP, were found for bedaquiline-pretomanid and linezolid-containing pairs, respectively. In contrast, subadditive and additive effects on rRNA synthesis were found for pretomanid-linezolid and bedaquiline-containing pairs, respectively. Additionally, accurate predictions of the response to BPaL for all three PD markers were made using only the single-drug and pairwise effects together with an assumption of negligible three-way drug interactions. The results represent an experimental and PD modeling approach aimed at reducing combinatorial complexity and improving the cost-effectiveness of
in vivo
systems for preclinical TB regimen development.
Biochemical analysis of the host factor activity of ZCCHC14 in hepatitis A virus replication
Authors: Li You , Lemon Stanley M.
Published: March 2024

Relatively little is known of the mechanisms underlying hepatitis A virus (HAV) genome replication. Unlike other well-studied picornaviruses, HAV RNA replication requires the zinc finger protein ZCCHC14 and non-canonical TENT4 poly(A) polymerases with which it forms a complex. The ZCCHC14–TENT4 complex binds to a stem-loop located within the internal ribosome entry site (IRES) in the 5’ untranslated RNA (5’UTR) and is essential for viral RNA synthesis, but the underlying mechanism is unknown. Here, we describe how different ZCCHC14 domains contribute to its RNA-binding, TENT4-binding, and HAV host factor activities. We show that the RNA-binding activity of ZCCHC14 requires both a sterile alpha motif (SAM) and a downstream unstructured domain (D4) and that ZCCHC14 contains two TENT4-binding sites: one at the N-terminus and the other around D4. Both RNA-binding and TENT4-binding are required for HAV host factor activity of ZCCHC14. We also demonstrate that the location of the ZCCHC14-binding site within the 5’UTR is critical for its function. Our study provides a novel insight into the function of ZCCHC14 and helps elucidate the mechanism of the ZCCHC14–TENT4 complex in HAV replication.

IMPORTANCE

The zinc finger protein ZCCHC14 is an essential host factor for both hepatitis A virus (HAV) and hepatitis B virus (HBV). It recruits the non-canonical TENT4 poly(A) polymerases to viral RNAs and most likely also a subset of cellular mRNAs. Little is known about the details of these interactions. We show here the functional domains of ZCCHC14 that are involved in binding to HAV RNA and interactions with TENT4 and describe previously unrecognized peptide sequences that are critical for the HAV host factor activity of ZCCHC14. Our study advances the understanding of the ZCCHC14–TENT4 complex and how it functions in regulating viral and cellular RNAs.
Semen enhances transmitted/founder HIV-1 infection and only marginally reduces antiviral activity of broadly neutralizing antibodies
Authors: von Maltitz Pascal , Wettstein Lukas , Weil Tatjana , Schommers Philipp , Klein Florian , Münch Jan
Published: March 2024

Topically applied microbicides may play a critical role in preventing sexual transmission of human immunodeficiency virus type 1 (HIV-1); however, their efficacy can be compromised by amyloid fibrils present in semen, which significantly increase HIV-1 infectivity. This phenomenon may have contributed to the failure of most microbicide candidates in clinical settings. Understanding the impact of semen on microbicide effectiveness is thus crucial. In our study, we evaluated the influence of semen on the neutralizing activity of broadly neutralizing antibodies (bNAbs), including PG16, PGT121, 10–1074, 3BNC117, and VRC01, which are potential microbicide candidates. We found that semen enhances infection of HIV-1 transmitted/founder viruses but only marginally affects the neutralizing activity of tested antibodies, suggesting their potential for microbicide application. Our findings underscore the need to consider semen-mediated enhancement when evaluating and developing microbicides and highlight the potential of incorporating HIV-1 bNAbs in formulations to enhance efficacy and mitigate HIV-1 transmission during sexual encounters.

IMPORTANCE

This study examined the impact of semen on the development of microbicides, substances used to prevent the transmission of HIV-1 during sexual activity. Semen contains certain components that can render the virus more infectious, posing a challenge to microbicide effectiveness. Researchers specifically investigated the effect of semen on a group of powerful antibodies called broadly neutralizing antibodies, which can neutralize a large spectrum of different HIV-1 variants. The results revealed that semen only had a minimal effect on the antibodies' ability to neutralize the virus. This is promising because it suggests that these antibodies could still be effective in microbicides, even in the presence of semen. Understanding this interaction is crucial for developing better strategies to prevent HIV-1 transmission. By incorporating the knowledge gained from this study, scientists can now focus on creating microbicides that consider the impact of semen, bringing us closer to more effective prevention methods.
Ehrlichia
effector TRP120 manipulates bacteremia to facilitate tick acquisition
Authors: Zhang Tsian , Chien Rory C. , Budachetri Khemraj , Lin Mingqun , Boyaka Prosper , Huang Weiyan , Rikihisa Yasuko
Published: March 2024

Ehrlichia
species are obligatory intracellular bacteria that cause a potentially fatal disease, human ehrlichiosis. The biomolecular mechanisms of tick acquisition of
Ehrlichia
and transmission between ticks and mammals are poorly understood.
Ehrlichia japonica
infection of mice recapitulates the full spectrum of human ehrlichiosis. We compared the pathogenicity and host acquisition of wild-type
E. japonica
with an isogenic transposon mutant of
E. japonica
that lacks tandem repeat protein 120 (TRP120) (ΔTRP120). Both wild-type and ΔTRP120
E. japonica
proliferated similarly in cultures of mammalian and tick cells. Upon inoculation into mice, both wild-type and ΔTRP120
E. japonica
multiplied to high levels in various tissues, with similar clinical chemistry and hematologic changes, proinflammatory cytokine induction, and fatal disease. However, the blood levels of ΔTRP120
E. japonica
were almost undetectable within 24 h, whereas the levels of the wild type increased exponentially. Greater than 90% of TRP120 was released from infected cells into the culture medium. Mouse blood monocytes exposed to native TRP120 from culture supernatants showed significantly reduced cell surface expression of the transmigration-related markers Ly6C and CD11b. Larval ticks attached to mice infected with either wild-type or ΔTRP120
E. japonica
imbibed similar amounts of blood and subsequently molted to nymphs at similar rates. However, unlike wild-type
E. japonica
, the ΔTRP120 mutant was minimally acquired by larval ticks and subsequent molted nymphs and, thus, failed to transmit to naïve mice. Thus, TRP120 is required for bacteremia but not disease. These findings suggest a novel mechanism whereby an obligatory intracellular bacterium manipulates infected blood monocytes to sustain the tick–mammal transmission cycle.

IMPORTANCE

Effective prevention of tick-borne diseases such as human ehrlichiosis requires an understanding of how disease-causing organisms are acquired.
Ehrlichia
species are intracellular bacteria that require infection of both mammals and ticks, involving cycles of transmission between them. Mouse models of ehrlichiosis and tick–mouse transmission can advance our fundamental understanding of the pathogenesis and prevention of ehrlichiosis. Herein, a mutant of
Ehrlichia japonica
was used to investigate the role of a single
Ehrlichia
factor, named tandem repeat protein 120 (TRP120), in infection of mammalian and tick cells in culture, infection and disease progression in mice, and tick acquisition of
E. japonica
from infected mice. Our results suggest that TRP120 is necessary only for
Ehrlichia
proliferation in circulating mouse blood and ongoing bacteremia to permit
Ehrlichia
acquisition by ticks. This study provides new insights into the importance of bacterial factors in regulating bacteremia, which may facilitate tick acquisition of pathogens.
Draft genome of
Kazachstania heterogenica var. weizmannii
, a commensal fungus of the mouse digestive tract
Authors: Kralova Jarmila Sekeresova , Fidel Lena , Donic Catalina , Ben-Dor Shifra , Jung Steffen
Published: March 2024

Kazachstania heterogenica
is a member of the
K. telluris
complex, where all members to date are reported to be pathogenic fungi. We have isolated a strain,
K. heterogenica var. weizmannii,
from the gut of mice that seems to be a commensal strain and sequenced its genome.
Genome sequence and annotation of
Pyramidobacter
sp. strain YE332, isolated from a cattle rumen fermentation of Leucaena leaf
Authors: Gilbert Rosalind , Davis Carl , Gravel Jenny , Ouwerkerk Diane
Published: March 2024

We report the 2.78-Mb circular genome sequence of
Pyramidobacter
sp. strain YE332, isolated from a fermentation of bovine rumen fluid, supplied with leaf material from
Leucaena leucocephala
cv. Cunningham. This genome sequence consists of 2,795,328 bp with 60% G + C content, 2,573 predicted coding DNA sequences, and 70 RNAs.
Draft genome sequence of
Acinetobacter baumannii
Ab10, a clinical isolate from Hospital University Sains Malaysia (HUSM), Malaysia
Authors: Nik Mohd Nazri Nik Zakuan Hakim , Banga Singh Kirnpal Kaur , Ismail Mohamad Izwan
Published: March 2024

Acinetobacter baumannii
strain Ab10 retrieved in Malaysia in 2017 represents a pathogen carrying multiple antibiotic-resistant genes (
blaOXA-23
,
ant(3”)-Ila
,
blaADC-32
, and
blaOXA-699
). We introduce the 3.89 Mbp genome sequence from short-read sequencing (Illumina’s NovaSeq6000).
Draft genome sequence of thermotolerant
Saccharomyces cerevisiae
AH465, isolated from Mt. Tatsuda, Kumamoto, Japan
Authors: Sasano Yu , Hamaguchi Ayuki , Taguchi Hisataka
Published: March 2024

Thermotolerance is a required characteristic for biofuel production by yeast. Here, we report the draft genome sequence of thermotolerant
Saccharomyces cerevisiae
AH465, which was originally isolated by the authors. A hybrid assembly approach using MinION Mk1b and MiSeq sequencers was conducted. The assembled sequence comprises 13.4 Mb in 26 contigs.
Complete genome sequences of
Lactobacillus acidophilus
strain P42 and
Limosilactobacillus reuteri
strain P43 isolated from chicken cecum
Authors: Hassan Hosni M. , Mendoza Mary , Dickey Allison N.
Published: March 2024

The gut microflora contains a diverse microbial population that is influenced by the host and the environment. We report the complete circular genome sequences of
Lactobacillus acidophilus
strain P42 and
Limosilactobacillus reuteri
strain P43 isolated from chicken cecal samples. P42 and P43 could potentially serve as poultry probiotic strains.
Genome sequence of white spot syndrome virus (WSSV) infecting cultured black tiger shrimp (
Penaeus monodon
) in Bangladesh
Authors: Islam S. M. Rafiqul , Ahmed Robel , Sharmen Farjana , Hossain Md. Mobarok , Chakma Kallyan , Tanni Afroza Akter , Akash Md. Ashikur Alim , Hossain Mohammad Enayet , Chowdhury M. Shah Nawaz , Siddiki AMAM Zonaed , Hossain Anwar , Mandal Shankar C. , Crandall Keith A. , Rahnavard Ali , Sharifuzzaman SM , Mannan Adnan
Published: March 2024

The white spot syndrome virus (WSSV) is a causative agent of white spot disease (WSD) in crustaceans, especially in cultivated black tiger shrimp (
Penaeus monodon
), leading to significant economic losses in the aquaculture sector. The present study describes four whole genome sequences of WSSV obtained from coastal regions of Bangladesh.
Temporal dynamics of
Candida albicans
morphogenesis and gene expression reveals distinctions between
in vitro
and
in vivo
filamentation
Authors: Wakade Rohan S. , Wellington Melanie , Krysan Damian J.
Published: March 2024

Candida albicans
is a common human fungal pathogen that is also a commensal of the oral cavity and gastrointestinal tract.
C. albicans
pathogenesis is linked to its transition from budding yeast to filamentous morphologies including hyphae and pseudohyphae. The centrality of this virulence trait to
C. albicans
pathobiology has resulted in extensive characterization of a wide range of factors associated with filamentation with a strong focus on transcriptional regulation. The vast majority of these experiments have used
in vitro
conditions to induce the yeast-to-filament transition. Taking advantage of
in vivo
approaches to quantitatively characterize both morphology and gene expression during filamentation during mammalian infection, we have investigated the dynamics of these two aspects of filamentation
in vivo
and compared them to
in vitro
filament induction with “host-like” tissue culture media supplemented with serum at mammalian body temperature. Although filamentation shares many common features in the two conditions, we have found two significant differences. First, alternative carbon metabolism genes are expressed early during
in vitro
filamentation and late
in vivo
, suggesting significant differences in glucose availability. Second,
C. albicans
begins a hyphae-to-yeast transition after 4-h incubation while we find little evidence of hyphae-to-yeast transition
in vivo
up to 24 h post-infection. We show that the low rate of
in vivo
hyphae-to-yeast transition is likely due to the very low expression of
PES1
, a key driver of lateral yeast
in vitro
and that heterologous expression of
PES1
is sufficient to trigger lateral yeast formation
in vivo
.

IMPORTANCE

Candida albicans
filamentation is correlated with virulence and is an intensively studied aspect of
C. albicans
biology. The vast majority of studies on
C. albicans
filamentation are based on
in vitro
induction of hyphae and pseudohyphae. Here we used an
in vivo
filamentation assay and
in vivo
expression profiling to compare the tempo of morphogenesis and gene expression between
in vitro
and
in vivo
filamentation. Although the hyphal gene expression profile is induced rapidly in both conditions, it remains stably expressed over a 12-h time course
in vivo
while it peaks after 4 h
in vitro
and is reduced. This reduced hyphal gene expression
in vitro
correlates with reduced hyphae and increased hyphae-to-yeast transition. By contrast, there is little evidence of hyphae-to-yeast transition
in vivo
.
Microbial species pool-mediated diazotrophic community assembly in crop microbiomes during plant development
Authors: Xiong Chao , K. Singh Brajesh , Zhu Yong-Guan , Hu Hang-Wei , Li Pei-Pei , Han Yan-Lai , Han Li-Li , Zhang Qin-Bing , Wang Jun-Tao , Liu Si-Yi , Wu Chuan-Fa , Ge An-Hui , Zhang Li-Mei , He Ji-Zheng
Published: March 2024

Plant-associated diazotrophs strongly relate to plant nitrogen (N) supply and growth. However, our knowledge of diazotrophic community assembly and microbial N metabolism in plant microbiomes is largely limited. Here we examined the assembly and temporal dynamics of diazotrophic communities across multiple compartments (soils, epiphytic and endophytic niches of root and leaf, and grain) of three cereal crops (maize, wheat, and barley) and identified the potential N-cycling pathways in phylloplane microbiomes. Our results demonstrated that the microbial species pool, influenced by site-specific environmental factors (e.g., edaphic factors), had a stronger effect than host selection (i.e., plant species and developmental stage) in shaping diazotrophic communities across the soil–plant continuum. Crop diazotrophic communities were dominated by a few taxa (~0.7% of diazotrophic phylotypes) which were mainly affiliated with
Methylobacterium
,
Azospirillum
,
Bradyrhizobium
, and
Rhizobium
. Furthermore, eight dominant taxa belonging to
Azospirillum
and
Methylobacterium
were identified as keystone diazotrophic taxa for three crops and were potentially associated with microbial network stability and crop yields. Metagenomic binning recovered 58 metagenome-assembled genomes (MAGs) from the phylloplane, and the majority of them were identified as novel species (37 MAGs) and harbored genes potentially related to multiple N metabolism processes (e.g., nitrate reduction). Notably, for the first time, a high-quality MAG harboring genes involved in the complete denitrification process was recovered in the phylloplane and showed high identity to
Pseudomonas mendocina
. Overall, these findings significantly expand our understanding of ecological drivers of crop diazotrophs and provide new insights into the potential microbial N metabolism in the phyllosphere.

IMPORTANCE

Plants harbor diverse nitrogen-fixing microorganisms (i.e., diazotrophic communities) in both belowground and aboveground tissues, which play a vital role in plant nitrogen supply and growth promotion. Understanding the assembly and temporal dynamics of crop diazotrophic communities is a prerequisite for harnessing them to promote plant growth. In this study, we show that the site-specific microbial species pool largely shapes the structure of diazotrophic communities in the leaves and roots of three cereal crops. We further identify keystone diazotrophic taxa in crop microbiomes and characterize potential microbial N metabolism pathways in the phyllosphere, which provides essential information for developing microbiome-based tools in future sustainable agricultural production.
The European livestock resistome
Authors: Munk Patrick , Yang Dongsheng , Röder Timo , Maier Leonie , Petersen Thomas Nordahl , Duarte Ana Sofia Ribeiro , Clausen Philip T. L. C. , Brinch Christian , Van Gompel Liese , Luiken Roosmarijn , Wagenaar Jaap A. , Schmitt Heike , Heederik Dick J. J. , Mevius Dik J. , Smit Lidwien A. M. ,   EFFORT Consortium, Bossers Alex , Aarestrup Frank M. , Graveland Haitske , Gonzalez-Zorn Bruno , Moyano Gabriel , Sanders Pascal , Chauvin Claire , Battisti Antonio , Dewulf Jeroen , Wadepohl Katharina , Wasyl Dariusz , Skarzyńska Magdalena , Zajac Magdalena , Pękala-Safińska Agnieszka , Daskalov Hristo , Stärk Katharina D. C.
Published: March 2024

Metagenomic sequencing has proven to be a powerful tool in the monitoring of antimicrobial resistance (AMR). Here, we provide a comparative analysis of the resistome from pigs, poultry, veal calves, turkey, and rainbow trout, for a total of 538 herds across nine European countries. We calculated the effects of per-farm management practices and antimicrobial usage (AMU) on the resistome in pigs, broilers, and veal calves. We also provide an in-depth study of the associations between bacterial diversity, resistome diversity, and AMR abundances as well as co-occurrence analysis of bacterial taxa and antimicrobial resistance genes (ARGs) and the universality of the latter. The resistomes of veal calves and pigs clustered together, as did those of avian origin, while the rainbow trout resistome was different. Moreover, we identified clear core resistomes for each specific food-producing animal species. We identified positive associations between bacterial alpha diversity and both resistome alpha diversity and abundance. Network analyses revealed very few taxa–ARG associations in pigs but a large number for the avian species. Using updated reference databases and optimized bioinformatics, previously reported significant associations between AMU, biosecurity, and AMR in pig and poultry farms were validated. AMU is an important driver for AMR; however, our integrated analyses suggest that factors contributing to increased bacterial diversity might also be associated with higher AMR load. We also found that dispersal limitations of ARGs are shaping livestock resistomes, and future efforts to fight AMR should continue to emphasize biosecurity measures.

IMPORTANCE

Understanding the occurrence, diversity, and drivers for antimicrobial resistance (AMR) is important to focus future control efforts. So far, almost all attempts to limit AMR in livestock have addressed antimicrobial consumption. We here performed an integrated analysis of the resistomes of five important farmed animal populations across Europe finding that the resistome and AMR levels are also shaped by factors related to bacterial diversity, as well as dispersal limitations. Thus, future studies and interventions aimed at reducing AMR should not only address antimicrobial usage but also consider other epidemiological and ecological factors.
A quorum-sensing regulatory cascade for siderophore-mediated iron homeostasis in
Chromobacterium violaceum
Authors: Batista Bianca B. , de Lima Vinicius M. , Picinato Beatriz A. , Koide Tie , da Silva Neto José F.
Published: March 2024

Iron is a transition metal used as a cofactor in many biochemical reactions. In bacteria, iron homeostasis involves Fur-mediated de-repression of iron uptake systems, such as the iron-chelating compounds siderophores. In this work, we identified and characterized novel regulatory systems that control siderophores in the environmental opportunistic pathogen
Chromobacterium violaceum
. Screening of a 10,000-transposon mutant library for siderophore halos identified seven possible regulatory systems involved in siderophore-mediated iron homeostasis in
C. violaceum
. Further characterization revealed a regulatory cascade that controls siderophores involving the transcription factor VitR acting upstream of the quorum-sensing (QS) system CviIR. Mutation of the regulator VitR led to an increase in siderophore halos, and a decrease in biofilm, violacein, and protease production. We determined that these effects occurred due to VitR-dependent de-repression of
vioS
. Increased VioS leads to direct inhibition of the CviR regulator by protein-protein interaction. Indeed, insertion mutations in
cviR
and null mutations of
cviI
and
cviR
led to an increase of siderophore halos. RNA-seq of the
cviI
and
cviR
mutants revealed that CviR regulates CviI-dependent and CviI-independent regulons. Classical QS-dependent processes (violacein, proteases, and antibiotics) were activated at high cell density by both CviI and CviR. However, genes related to iron homeostasis and many other processes were regulated by CviR but not CviI, suggesting that CviR acts without its canonical CviI autoinducer. Our data revealed a complex regulatory cascade involving QS that controls siderophore-mediated iron homeostasis in
C. violaceum
.

IMPORTANCE

The iron-chelating compounds siderophores play a major role in bacterial iron acquisition. Here, we employed a genetic screen to identify novel siderophore regulatory systems in
Chromobacterium violaceum
, an opportunistic human pathogen. Many mutants with increased siderophore halos had transposon insertions in genes encoding transcription factors, including a novel regulator called VitR, and CviR, the regulator of the quorum-sensing (QS) system CviIR. We found that VitR is upstream in the pathway and acts as a dedicated repressor of
vioS
, which encodes a direct CviR-inhibitory protein. Indeed, all QS-related phenotypes of a
vitR
mutant were rescued in a
vitRvioS
mutant. At high cell density, CviIR activated classical QS-dependent processes (violacein, proteases, and antibiotics production). However, genes related to iron homeostasis and type-III and type-VI secretion systems were regulated by CviR in a CviI- or cell density-independent manner. Our data unveil a complex regulatory cascade integrating QS and siderophores in
C. violaceum
.
Involvement of a putative acyltransferase gene in sporangium formation in
Actinoplanes missouriensis
Authors: Hu Shixuan , Maeda Satoshi , Tezuka Takeaki , Ohnishi Yasuo
Published: March 2024

The actinomycete
Actinoplanes missouriensis
forms branched substrate mycelia during vegetative growth and produces terminal sporangia, each of which contains a few hundred spherical flagellated spores, from the substrate mycelia through short sporangiophores. Based on the observation that remodeling of membrane lipid composition is involved in the morphological development of
Streptomyces coelicolor
A3(2), we hypothesized that remodeling of membrane lipid composition is also involved in sporangium formation in
A. missouriensis
. Because some acyltransferases are presumably involved in the remodeling of membrane lipid composition, we disrupted each of the 22 genes annotated as encoding putative acyltransferases in the
A. missouriensis
genome and evaluated their effects on sporangium formation. The
atsA
(
AMIS_52390
) null mutant (Δ
atsA
) strain formed irregular sporangia of various sizes. Transmission electron microscopy revealed that some Δ
atsA
sporangiospores did not mature properly. Phase-contrast microscopy revealed that sporangium dehiscence did not proceed properly in the abnormally small sporangia of the Δ
atsA
strain, whereas apparently normal sporangia opened to release the spores. Consistently, the number of spores released from Δ
atsA
sporangia was lower than that released from wild-type sporangia. These phenotypic changes were recovered by introducing
atsA
with its own promoter into the Δ
atsA
strain. These results demonstrate that AtsA is required for normal sporangium formation in
A. missouriensis
, although the involvement of AtsA in the remodeling of membrane lipid composition is unlikely because AtsA is an acyltransferase_3 (AT3) protein, which is an integral membrane protein that usually catalyzes the acetylation of cell surface structures.

IMPORTANCE

Actinoplanes missouriensis
goes through a life cycle involving complex morphological development, including mycelial growth, sporangium formation and dehiscence, swimming as zoospores, and germination to mycelial growth. In this study, we carried out a comprehensive gene disruption experiment of putative acyltransferase genes to search for acyltransferases involved in the morphological differentiation of
A. missouriensis
. We revealed that a stand-alone acyltransferase_3 domain-containing protein, named AtsA, is required for normal sporangium formation. Although the molecular mechanism of AtsA in sporangium formation, as well as the enzymatic activity of AtsA, remains to be elucidated, the identification of a putative acyltransferase involved in sporangium formation is significant in the study of morphological development of
A. missouriensis
. This finding will contribute to our understanding of a complex system for producing sporangia, a rare multicellular organism in bacteria.
Progress towards health equity in Vietnam: evidence from nationwide official health statistics, 2010-2020
Authors: Feng Yikai , Tuan Tran Diep , Shi Junyi , Li Zhuo , Maimaitiming Mailikezhati , Jin Yinzi , Zheng Zhijie
Published: March 2024

Introduction

One of the ultimate goals of strengthening the health system is to achieve health equity. Vietnam is considered one of the ‘fast-track countries’ to achieve the health-related Millennium Development Goals, but research on its equity strategies remains inadequate.

Methods

Using Vietnamese official health statistics, we investigated inequity in four dimensions including health resources, service delivery, service utilisation and residents’ health status from the perspectives of income levels, poverty rates and subnational regions. The Slope Index of Inequality, concentration curve/Concentration Index, absolute difference and Theil Index were used.

Results

Four indicators showed ‘pro-poor’ inequality in health resources, including the per capita health budget, per capita health personnel, per capita health personnel at the community level and per capita hospital beds at the community level, while provincial hospital beds showed ‘pro-rich’ inequality. Two health service delivery indicators (delivery of antenatal care ≥3 times and proportion of community health service centres with medical doctors) show ‘pro-rich’ inequality, although two health status indicators, mortality and malnutrition rates for children under five, showed ‘pro-poor’ inequality. The Northern Midlands and Mountain Areas, and the Central Highlands were disadvantaged regarding service delivery and health status. Intraregional differences were the main factors contributing to the inequalities in delivery of antenatal care ≥3 times, provincial hospital beds and percentage of community health centres with medical doctors, with the Red River Delta and the South East region experiencing the greatest inequalities.

Conclusion

The overall level of health equity in Vietnam has increased over the past decade, although inequality in health service delivery has hindered progress towards health equity based on income, poverty and subnational regions. Targeted policies need to be introduced to reduce inequities relating to the health workforce and service delivery capacity.
Geographical variation in perceptions, attitudes and barriers to mental health care-seeking across the UK: a cross-sectional study
Authors: Wang Rui Adele H , Smittenaar Peter , Thomas Tony , Kamal Zeast , Kemp Hannah , Sgaier Sema K
Published: March 2024

Objectives

To examine the relative importance of the drivers of mental health care-seeking intention and how these, along with intention itself, are geographically distributed across integrated care systems (ICS) and health boards (HBs) in the UK. Also, to examine the degree of acceptance of virtual modes of care.

Design

Community-based cross-sectional survey.

Participants and setting

A national online survey of 17 309 adults between August and September 2021 recruited via a research technology company, Lucid. Sample size quotas were set to ensure coverage across the UK and match population distributions for gender, age and ethnicity. After exclusions, 16 835 participants remained (54% female, 89% white).

Main outcome measures

Care-seeking intention, using a continuous measure of likelihood and a categorical measure of estimated time to seek professional help for a future mental health difficulty.

Results

20.5% (95% CI 19.8% to 21.2%) reported that they would significantly delay or never seek mental healthcare, ranging from 8.3% to 25.7% across ICS/HBs. Multilevel regression analysis showed mental health knowledge was the most predictive of care-seeking intention, followed by attitudes towards others with mental illness and a combination of stigma, negative attitudes to treatment and instrumental barriers to accessing care. The model explained 17% of the variance. There was substantial geographical variation in prevalence of preclinical symptoms of depression and anxiety, attitudes to mental health, and barriers to care, leading to complex ICS/HB profiles. Remote and self-guided therapies did not pose as a major barrier to care with more than half of respondents likely or very likely to use them.

Conclusions

Our locally relevant and actionable findings suggest possible interventions that may improve care-seeking intention and indicate which of these interventions need to be geographically tailored to have maximal effect.
Socioeconomic inequalities in skilled attendance at birth and caesarean section rates in Myanmar 2015–2016: a cross-sectional study
Authors: Show Kyaw Lwin , Maung Thae Maung , Disney George , Bohren Meghan A. , Lumbiganon Pisake , Ngamjarus Chetta
Published: March 2024

Objectives

This study aims to assess inequalities in skilled birth attendance and utilisation of caesarean section (CS) in Myanmar.

Study design

Cross-sectional study design.

Setting and population

We used secondary data from the Myanmar Demographic and Health Survey (2015–2016). Our outcome measures of skilled birth attendance and utilisation of CS were taken from the most recent birth of interviewed women. Absolute and relative inequalities across several sociodemographic characteristics were assessed and evaluated by calculating rate differences, rate ratio and concentration indexes.

Results

More than one-third (36%, 95% CI 32.5% to 39.4%) of women gave birth without a skilled birth attendant present at their most recent birth. 40.7% (95% CI 37.8% to 43.7%) gave birth in healthcare facilities, and the CS rate was 19.7% (95% CI 17.9% to 21.8%) for their most recent birth. The highest proportion of birth without a skilled provider was found in the hilly regions and rural residents, poorest and less educated women, and those with less than four antenatal care visits. Inequalities in birth without a skilled provider were observed across regions, place of residence, wealth quintile, education level and number of antenatal care taken. The highest rate of CS was found among plain regions and urban residents, richest women, more than secondary education, those with more than four antenatal care visits and in private health facilities. Inequalities in CS utilisation were observed across place of residence, wealth quintiles, education level, number of antenatal care taken and type of health facilities.

Conclusion

This study provides evidence regarding inequalities in maternal health service utilisation in Myanmar. Increasing maternal health service availability and accessibility, promoting quality of care and health education campaigns to increase maternal health services utilisation are recommended.
Association of thyroid autoantibodies and diabetic kidney disease in hospitalised patients with type 2 diabetes mellitus: a cross-sectional study from a Chinese university hospital
Authors: Wang Zhi , Wang Futao , Liu Cong , Zhang Le
Published: March 2024

Objectives

To analyse and explore the association between thyroid autoantibodies and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM).

Design

A cross-sectional study.

Setting

Patients were from the inpatient unit at The Second Endocrinology Department of Shengjing Hospital Affiliated to China Medical University (Shenyang, China) between January 2015 and September 2019.

Participants

A total of 150 Chinese adults with T2DM were included in the study, including 83 men and 67 women. Their age ranged between 25 and 92 years.

Methodology

They grouped by the presence of DKD, urine albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate, and levels of thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb). Data on the patients’ general characteristics and laboratory measurements (levels of fasting plasma glucose, glycated haemoglobin, and albumin; renal function; and thyroid function) were collected. Binary logistic regression was performed to identify risk factors for DKD.

Results

The level of TPOAb, the positivity rates of TPOAb (p<0.01) and TgAb (p<0.05) were higher in patients with DKD than in those without DKD. The TPOAb level in patients with a UACR<30 mg/g creatinine was lower than that in patients with a UACR between 30 and 300 mg/g creatinine (p<0.05). The prevalence of DKD was higher in patients with a TPOAb-positive or TgAb-positive status. The result of binary logistic regression analysis showed that a TPOAb-positive status was significantly associated with DKD in patients with T2DM (OR=7.683, 95% CI 1.583 to 37.286, p<0.05).

Conclusions

TPOAb-positive status is in association with DKD in patients with T2DM. Large scale, prospective cohort studies are warranted to confirm our findings.
Exploring young people’s attitudes to HIV prevention medication (PrEP) in England: a qualitative study
Authors: Rathbone Adam , Cartwright Nia , Cummings Lewis , Noble Rebecca , Budaiova Kristina , Ashton Mark , Foster Jonathan , Payne Brendan , Duncan Sarah
Published: March 2024

Introduction

Young people aged 18–24 years old are a key demographic target for eliminating HIV transmission globally. Pre-exposure prophylaxis (PrEP), a prevention medication, reduces HIV transmission. Despite good uptake by gay and bisexual men who have sex with men, hesitancy to use PrEP has been observed in other groups, such as young people and people from ethnic minority backgrounds. The aim of this study was to explore young people’s perceptions and attitudes to using PrEP.

Design

A qualitative transcendental phenomenological design was used.

Participants and setting

A convenience sample of 24 young people aged between 18 and 24 years was recruited from England.

Methods

Semistructured interviews and graphical elicitation were used to collect data including questions about current experiences of HIV care, awareness of using PrEP and decision-making about accessing PrEP. Thematic and visual analyses were used to identify findings.

Results

Young people had good levels of knowledge about HIV but poor understanding of using PrEP. In this information vacuum, negative stigma and stereotypes about HIV and homosexuality were transferred to using PrEP, which were reinforced by cultural norms portrayed on social media, television and film—such as an association between using PrEP and being a promiscuous, white, gay male. In addition, young people from ethnic minority communities appeared to have negative attitudes to PrEP use, compared with ethnic majority counterparts. This meant these young people in our study were unable to make decisions about when and how to use PrEP.

Conclusion

Findings indicate an information vacuum for young people regarding PrEP. A strength of the study is that theoretical data saturation was reached. A limitation of the study is participants were largely from Northern England, which has low prevalence of HIV. Further work is required to explore the information needs of young people in relation to PrEP.