bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatitis C virus modified sE2
F442NYT
as an antigen in candidate vaccine facilitates human immune cell activation
Authors: Haga Yuki , Meyer Keith , Sung Molly M. H. , Reagan Erin K. , Weissman Drew , Ray Ranjit 
Published: December 2023

ABSTRACT

The rational selection of hepatitis C virus (HCV) vaccine antigen will aid in the prevention of future chronic liver disease burden and associated healthcare costs. We have previously shown that HCV E2 glycoprotein is not highly immunogenic, and the modification of E2 reduced CD81 binding and displayed altered cytokine and protective immune responses
in vitro
and in a surrogate mouse model. Here, we compared the influence of a parental and a modified sE2
F442NYT
glycoprotein region from HCV genotype 1a for the activation of peripheral blood mononuclear cell (PBMC)-derived dendritic cells (DCs), CD4
+
T cells, and B cells. Modified sE2
F442NYT
, when incubated with DCs, induced a higher number of CD86-positive cells. The sE2
F442NYT
or parental sE2 encapsulated as mRNA-lipid nanoparticle (sE2
F442NYT
mRNA-LNP) primed DCs co-cultured with autologous CD4
+
T cells did not induce CD25 or forkhead box P3 expression. PBMC-derived CD4
+
T cells treated with sE2
F442NYT
exhibited enhanced signal transducer and activator of transcription (Stat)1/Stat4 phosphorylation in response to anti-CD3/CD28 stimulation in comparison to parental sE2 treatment and facilitated isotype switching in B cells, leading to the generation of a broader subclass of antibodies. Cells treated with modified sE2
F442NYT
displayed an increase in activated Stat3 and extracellular signal-regulated kinase (ERK). Likewise, PBMC-derived naïve B cells upon
in vitro
stimulation with sE2
F442NYT
induced an increased proliferation, Stat3 and ERK activation, and protein kinase B (Akt) suppression. Thus, the modified sE2
F442NYT
antigen from HCV facilitates improved DC, CD4
+
T, and B cell activation compared to parental sE2 to better induce a robust protective immune response, supporting its selection as an HCV candidate vaccine antigen for preclinical and clinical HCV vaccine trials.

IMPORTANCE

The nature of an enhanced immune response induced by sE2
F442NYT
will help in the selection of a broad cross-protective antigen from hepatitis C virus genotypes, and the inclusion of relatively conserved sE1 with sE2
F442NYT
may further strengthen the efficacy of the candidate vaccine in evaluating it for human use.
Mentoring across difference and distance: building effective virtual research opportunities for underrepresented minority undergraduate students in biological sciences
Authors: Knox Corey J. , Ab Latif Faqryza M. , Cornejo Natasha R. , Johnson Michael D. L. 
Published: December 2023

ABSTRACTThe National Summer Undergraduate Research Program (NSURP) is a mentored summer research program in biosciences for undergraduate students from underrepresented backgrounds in science, technology, engineering, and mathematics (STEM). Conducted virtually over 8 weeks every summer starting in 2020, NSURP provides accessible and flexible research experiences to meet the needs of geographically diverse and schedule-constrained students. Drawing from mentee reporting and surveys conducted within the NSURP framework involving over 350 underrepresented minority undergraduate students over three cohorts (2020–2022), matched with mentors, this paper highlights the potential benefits of students participating in virtual mentored research experiences. In addition to increased access to quality research experiences for students who face travel or academic setting constraints, we found that virtual mentoring fosters cross-cultural collaborations, generates novel research questions, and expands professional networks. Moreover, this study emphasizes the role of virtual mentorship opportunities in fostering inclusivity and support for individuals from underrepresented groups in STEM fields. By overcoming barriers to full participation in the scientific community, virtual mentorship programs can create a more equitable and inclusive environment for aspiring researchers. This research contributes to the growing body of literature on the effectiveness and the potential of virtual research programs and mentorship opportunities in broadening participation and breaking down barriers in STEM education and careers.IMPORTANCESummer Research Experiences for Undergraduates (REUs) are established to provide platforms for interest in scientific research and as tools for eventual matriculation to scientific graduate programs. Unfortunately, the COVID-19 pandemic forced the cancellation of in-person programs for 2020 and 2021, creating the need for alternative programming. The National Summer Undergraduate Research Project (NSURP) was created to provide a virtual option to REUs in microbiology to compensate for the pandemic-initiated loss of research opportunities. Although in-person REUs have since been restored, NSURP currently remains an option for those unable to travel to in-person programs in the first place due to familial, community, and/or monetary obligations. This study examines the effects of the program's first 3 years, documenting the students’ experiences, and suggests future directions and areas of study related to the impact of virtual research experiences on expanding and diversifying science, technology, engineering, and mathematics.
Evidence for Rho-dependent control of a virulence switch in
Acinetobacter baumannii
Authors: Pérez-Varela María , Singh Raja , Colquhoun Jennifer M. , Starich Olivia G. , Tierney Aimee R. P. , Tipton Kyle A. , Rather Philip N. 
Published: December 2023

ABSTRACT

Acinetobacter baumannii
strain AB5075 is able to interconvert at high frequency between virulent cells that form opaque colonies (VIR-O) and avirulent cells that form translucent colonies (AV-T). Cells switch from the VIR-O to the AV-T state by the combinatorial activation of at least three TetR-type transcriptional regulators (TTTRs). A genetic screen identified the transcription termination factor Rho as a major contributor that controls expression differences of these TTTRs between VIR-O and AV-T cells. Each TTTR has a long mRNA leader region where transcripts are terminated in VIR-O cells. However, in AV-T cells, the degree of termination in each TTTR leader was greatly reduced, allowing for higher levels of TTTR expression. In a strain with decreased Rho expression, or in wild-type VIR-O cells treated with the Rho inhibitor bicyclomycin, the degree of termination in each TTTR mRNA leader region was reduced. Mutations in the leader region of one TTTR,
ABUW_1645
, were identified that reduced the degree of termination. Purified Rho protein bound the leader region of the most frequently activated TTTR
ABUW_1645
and the least frequently activated TTTR
ABUW_1959
with similar affinities. This together with the observation that the levels of Rho protein were unchanged between VIR-O and AV-T cells, suggested that additional factors differentially modulate Rho activity between each variant. Finally, we demonstrate in AV-T cells that nutrient depletion is a condition that increases the levels of Rho-dependent transcription termination in the TTTR leader regions to regulate this phenotypic switch.

IMPORTANCE

Acinetobacter baumannii
is a significant cause of infections in the healthcare setting. More recently,
A. baumannii
has been a leading cause of secondary bacterial pneumonia in patients infected with SARS-CoV-2 and the overall frequency of
A. baumannii
infection increased 78% during the COVID-19 pandemic.
A. baumannii
can exist in virulent or avirulent subpopulations and this interconversion is mediated by the expression of a family of TetR-type transcriptional regulators. In this study, we demonstrate that Rho is a key regulatory component in the expression of these TetR regulators. Overall, this study is the first to address a role for Rho in
A. baumannii
and provides additional evidence for the role of Rho in regulating diversity in bacterial subpopulations.
Type IV pilus retraction is required for
Neisseria musculi
colonization and persistence in a natural mouse model of infection
Authors: Rhodes Katherine A. , Rendón María A. , Ma Man Cheong , Agellon Al , Johnson Andrew C.E. , So Magdalene 
Published: December 2023

ABSTRACT

Retraction of the pathogenic
Neisseria
Type IV pilus (Tfp) requires PilT, the primary retraction motor, and its paralogs PilU and PilT2. The importance of Tfp retraction for natural infection is unknown. Using our natural animal model of
Neisseria
-host interaction, we have examined the role of these proteins in the ability of commensal
Neisseria musculi
(Nmus) to colonize and persist in its native host, the mouse. We report that Nmus Δ
pilT
cannot colonize mice; Δ
pilU
and Δ
pilT2
can colonize and persist in mice, but in lower numbers. Microcolonies formed by Δ
pilT
, Δ
pilTU
, and

pilT
L201C

, expressing PilT with a point mutation in its ATP hydrolysis domain, are sensitive to removal by fluid shear forces. Thus, PilT promotes Nmus colonization while PilU and PilT2 influence persistence. We present a non-exclusive model for how these Tfp retraction motor proteins contribute to Nmus persistent colonization. Our findings have implications for the roles of these motor proteins in mediating interactions of human-adapted pathogenic and commensal
Neisseria
with their human host.

IMPORTANCE

We describe the importance of Type IV pilus retraction to colonization and persistence by a mouse commensal
Neisseria, N. musculi,
in its native host. Our findings have implications for the role of Tfp retraction in mediating interactions of human-adapted pathogenic and commensal
Neisseria
with their human host due to the relatedness of these species.
Sua5 catalyzing universal t
6
A tRNA modification is responsible for multifaceted functions of the KEOPS complex in
Cryptococcus neoformans
Authors: Choi Yeseul , Hyeon Hana , Lee Kangseok , Bahn Yong-Sun 
Published: December 2023

ABSTRACT

The N
6
-threonylcarbamoyl adenosine (t
6
A) tRNA modification is critical for ensuring translation fidelity across three domains of life. Our prior work highlighted the KEOPS complex, organized in a Pcc1-Kae1-Bud32-Cgi121 linear arrangement, not only serves an evolutionarily conserved role in t
6
A tRNA modification but also exerts diverse functional impacts on pathobiological characteristics in
Cryptococcus neoformans
, a leading cause of fungal meningitis worldwide. However, the extent to which the pleiotropic functions of the KEOPS complex are specifically tied to tRNA modification remains uncertain. To address this, we undertook a functional characterization of Sua5, responsible for generating the precursor threonylcarbamoyl-adenylate (TC-AMP) for t
6
A tRNA modification, using a reverse genetics approach. Comparative phenotypic analyses with KEOPS mutants revealed that Sua5 plays a vital role in multiple cellular processes, such as t
6
A tRNA modification, growth, sexual development, stress response, and virulence factor production, thus reflecting the multifaceted functions of the KEOPS complex. In support of this,
sua5
Δ
bud32
Δ double mutants showed phenotypes comparable to those of the corresponding single mutants. Intriguingly, a
SUA5
allele lacking a mitochondria targeting sequence (

SUA5
MTS

Δ
) was sufficient to restore the wild-type phenotypes in the
sua5
Δ mutant, suggesting that Sua5’s primary functional locus may be cytosolic, akin to the KEOPS complex. Further supporting this, the deletion of Qri7, a mitochondrial paralog of Kae1, had no discernible phenotypic impact on
C. neoformans
. We concluded that cytosolic t
6
A tRNA modifications, orchestrated by Sua5 and the KEOPS complex, are central to the regulation of diverse pathobiological functions in
C. neoformans
.

IMPORTANCE

Understanding cellular functions at the molecular level is crucial for advancing disease treatments. Our research reveals a critical connection between the KEOPS complex and Sua5 in
Cryptococcus neoformans
, a significant cause of fungal meningitis. While the KEOPS complex is known for its versatile roles in cellular processes, Sua5 is specialized in t
6
A tRNA modification. Our key finding is that the diverse roles of the KEOPS complex, ranging from cell growth and stress response to virulence, are fundamentally linked to its function in t
6
A tRNA modification. This conclusion is supported by the remarkable similarities between the impacts of Sua5 and KEOPS on these processes, despite their roles in different steps of the t
6
A modification pathway. This newfound understanding deepens our insight into fungal biology and opens new avenues for developing potential therapies against dangerous fungal diseases.
Taxonomic and functional assembly cues enrich the endophytic tobacco microbiota across epiphytic compartments
Authors: Yang Luhua , Guo Yuan , Yang Hui , Li Shun , Zhang Yunzeng , Hao Likai 
Published: December 2023

ABSTRACT
The plant microbiome plays a critical role in plant growth, development, and health, with endophytes being recognized as essential members due to their close interactions with host plants. However, knowledge gaps remain in understanding the mechanisms driving the colonization and establishment of endophytic communities. To address this issue, we investigated the microbiota of tobacco roots and leaves, including both epiphytic and endophytic microorganisms. We found that Actinobacteria and Alphaproteobacteria were significantly enriched in the root endosphere. Additionally, we identified higher abundances of functional traits involved in antibiotic synthesis, plant cell wall degradation, iron metabolism, secretion systems, and nicotine degradation enzymes in the endosphere. We further studied metagenome-assembled genomes from the rhizosphere and root endosphere, revealing a greater diversity of secondary metabolites in bacteria within the root endosphere. Together, this study provides insights into the taxonomic and functional assembly cues that may contribute to shaping the endophytic plant microbiota.

IMPORTANCE
The presence of diverse microorganisms within plant tissues under natural conditions is a well-established fact. However, due to the plant immune system’s barrier and the unique microhabitat of the plant interior, it remains unclear what specific characteristics bacteria require to successfully colonize and thrive in the plant endosphere. Recognizing the significance of unraveling these functional features, our study focused on investigating the enriched traits in the endophytic microbiota compared to the epiphytes. Through our research, we have successfully identified the taxonomic and functional assembly cues that drive the enrichment of the endophytic microbiota across the epiphytic compartments. These findings shed new light on the intricate mechanisms of endophyte colonization, thereby deepening our understanding of plant-microbe interactions and paving the way for further advancements in microbiome manipulation.
Mycothione reductase as a potential target in the fight against
Mycobacterium abscessus
infections
Authors: Piller T. , De Vooght L. , Gansemans Y. , Van Nieuwerburgh F. , Cos P. 
Published: December 2023

ABSTRACT

While infections caused by
Mycobacterium abscessus
complex (MABC) are rising worldwide, the current treatment of these infections is far from ideal due to its numerous shortcomings thereby increasing the urge for novel drug targets. In this study, mycothione reductase (Mtr) was evaluated for its potential as a drug target for MABC infections since it is a key enzyme needed in the recycling of mycothiol, the main low-molecular-weight thiol protecting the bacteria against reactive oxygen species and other reactive intermediates. First, a
Mab
∆
mtr
mutant strain was generated, lacking
mtr
expression. Next, the
in vitro
sensitivity of
Mab
∆
mtr
to oxidative stress and antimycobacterial drugs was determined. Finally, we evaluated the intramacrophage survival and the virulence of
Mab
∆
mtr
in
Galleria mellonella
larvae.
Mab
∆
mtr
demonstrated a 39.5-fold reduction in IC90 when exposed to bedaquiline
in vitro
. Furthermore, the
Mab
∆
mtr
mutant showed a decreased ability to proliferate inside macrophages and larvae, suggesting that Mtr plays an important role during MABC infection. Altogether, these findings support the assumption of Mtr being a potential target for antimycobacterial drugs.

IMPORTANCE

Mycobacterium abscessus
complex (MABC) is a group of bacteria causing a serious public health problem worldwide due to its ability to cause progressive disease, its highly resistant profile against various antibiotics, and its lengthy treatment. Therefore, new drugs are needed to alleviate antibiotic resistance and reduce the length of the current treatment. A potential new target for new antibiotics is mycothione reductase (Mtr), an important enzyme belonging to a pathway that protects the bacteria against harmful conditions. Our research created a bacterium deficient of
mtr
by using advanced genetic techniques and demonstrated that
mtr
-deficient bacteria have a decreased ability to multiply during infection. Furthermore, we show evidence that currently used antibiotics combined with
mtr
deficiency can lead to a better treatment of MABC infection. Altogether, our results validate Mtr as a potential new target and suggest that Mtr plays a role during MABC infection.
Fecal microbial gene transfer contributes to the high-grain diet-induced augmentation of aminoglycoside resistance in dairy cattle
Authors: Zhang Tao , Mu Yingyu , Gao Yunlong , Tang Yijun , Mao Shengyong , Liu Jinxin 
Published: December 2023

ABSTRACT

A high-grain (HG) diet can rapidly lower the rumen pH and thus modify the gastrointestinal microbiome in dairy cattle. Although the prevalence of antibiotic resistance is strongly linked with the gut microbiome, the influences of HG diet on animals’ gut resistome remain largely unexplored. Here, we examined the impact and mechanism of an HG diet on the fecal resistome in dairy cattle by metagenomically characterizing the gut microbiome. Eight lactating Holstein cattle were randomly allocated into two groups and fed either a conventional (CON) or HG diet for 3 weeks. The fecal microbiome and resistome were significantly altered in dairy cattle from HG, demonstrating an adaptive response that peaks at day 14 after the dietary transition. Importantly, we determined that feeding an HG diet specifically elevated the prevalence of resistance to aminoglycosides (0.11 vs 0.24 RPKG,
P
< 0.05). This diet-induced resistance increase is interrelated with the disproportional propagation of microbes in Lachnospiraceae, indicating a potential reservoir of aminoglycosides resistance. We further showed that the prevalence of acquired resistance genes was also modified by introducing a different diet, likely due to the augmented frequency of lateral gene transfer (LGT) in microbes (CON vs HG: 254 vs 287 taxa) such as Lachnospiraceae. Consequently, we present that diet transition is associated with fecal resistome modification in dairy cattle and an HG diet specifically enriched aminoglycosides resistance that is likely by stimulating microbial LGT.

IMPORTANCE
The increasing prevalence of antimicrobial resistance is one of the most severe threats to public health, and developing novel mitigation strategies deserves our top priority. High-grain (HG) diet is commonly applied in dairy cattle to enhance animals’ performance to produce more high-quality milk. We present that despite such benefits, the application of an HG diet is correlated with an elevated prevalence of resistance to aminoglycosides, and this is a combined effect of the expansion of antibiotic-resistant bacteria and increased frequency of lateral gene transfer in the fecal microbiome of dairy cattle. Our results provided new knowledge in a typically ignored area by showing an unexpected enrichment of antibiotic resistance under an HG diet. Importantly, our findings laid the foundation for designing potential dietary intervention strategies to lower the prevalence of antibiotic resistance in dairy production.
Wetlands harbor lactic acid-driven chain elongators
Authors: Candry Pieter , Flinkstrom Zachary , Henriikka Winkler Mari-Karoliina 
Published: December 2023

ABSTRACT
Wetlands are globally significant carbon storage hotspots. Recent research has suggested that microbially derived metabolites may contribute to soil organic matter formation. Identifying pathways driving the formation of such metabolites is critical to understand the global impact of wetland carbon cycling. Here, we evaluate the presence of chain-elongating organisms converting two to three carbon compounds (i.e., lactic and acetic acid) to medium-chain carboxylic acids (MCCA; i.e., six-carbon caproic acid) in wetland soils. We demonstrate the enrichment of a lactic acid-driven chain-elongating community from wetland soils producing a mixture of butyric and caproic acid. The enriched community was dominated by Clostridiaceae, Ruminococcaceae, and Lachnospiraceae, three families with known chain elongators. Amplicon sequencing identified three Ruminococcaceae and one Clostridiaceae zero-radius OTU (zOTU) that were (i) present in the soil, (ii) enriched over 1% relative abundance in the bioreactor, and (iii) were closely related to known chain elongators. Moreover, close relatives of the three Ruminococcaceae zOTU were also observed in several other wetland microbiomes. From this observation, we conclude that close relatives of known chain elongators, potentially capable of lactic acid-driven MCCA production themselves, are present in wetland soils. This observation may have implications for our understanding of carbon cycling and storage in wetland ecosystems.

IMPORTANCE

Wetlands are globally significant carbon cycling hotspots that both sequester large amounts of CO
2
as soil carbon as well as emit a third of all CH
4
globally. Their outsized role in the global carbon cycle makes it critical to understand microbial processes contributing to carbon breakdown and storage in these ecosystems. Here, we confirm the presence of chain-elongating organisms in freshwater wetland soils. These organisms take small carbon compounds formed during the breakdown of biomass and turn them into larger compounds (six to eight carbon organic acids) that may potentially contribute to the formation of soil organic matter and long-term carbon storage. Moreover, we find that these chain-elongating organisms may be widely distributed in wetlands globally. Future work should identify these organisms’ contribution to carbon cycling in wetlands and the potential role of the products they form in carbon sequestration in wetlands.
Controls on topography and erosion of the north-central Andes
Authors: Leonard Joel S. , Whipple Kelin X. , Heimsath Arjun M. 
Published: December 2023

Abstract
We present 17 new 10Be erosion rates from southern Peru sampled across an extreme orographic rainfall gradient. Using a rainfall-weighted variant of the normalized channel steepness index, ksnQ, we show that channel steepness values, and thus topography, are adjusted to spatially varying rainfall. Rocks with similar physical characteristics define distinct relationships between ksnQ and erosion rate (E), suggesting ksnQ is also resolving lithologic variations in erodibility. However, substantial uncertainty exists in parameters describing these relationships. By combining our new data with 38 published erosion rates from Peru and Bolivia, we collapse the range of compatible parameter values and resolve robust, nonlinear ksnQ–E relationships suggestive of important influences of erosional thresholds, rock properties, sediment characteristics, and temporal runoff variability. In contrast, neither climatic nor lithologic effects are clear using the traditional channel steepness metric, ksn. Our results highlight that accounting for spatial rainfall variations is essential for disentangling the multiple influences of climate, lithology, and tectonics common in mountain landscapes, which is a necessary first step toward greater understanding of how these landscapes evolve.