bluuebunny/crossref_metadata_2025_split huggingface dataset:
Macaque antibodies targeting Marburg virus glycoprotein induced by multivalent immunization
Authors: Janus Benjamin M. , Wang Ruixue , Cleveland Thomas E. , Metcalf Matthew C. , Lemmer Aaron C. , van Dyk Nydia , Jeong Sarah , Astavans Anagh , Class Kenneth , Fuerst Thomas R. , Ofek Gilad 
Published: June 2024

ABSTRACT

Marburg virus infection in humans is associated with case fatality rates that can reach up to 90%, but to date, there are no approved vaccines or monoclonal antibody (mAb) countermeasures. Here, we immunized Rhesus macaques with multivalent combinations of filovirus glycoprotein (GP) antigens belonging to Marburg, Sudan, and Ebola viruses to generate monospecific and cross-reactive antibody responses against them. From the animal that developed the highest titers of Marburg virus GP-specific neutralizing antibodies, we sorted single memory B cells using a heterologous Ravn virus GP probe and cloned and characterized a panel of 34 mAbs belonging to 28 unique lineages. Antibody specificities were assessed by overlapping pepscan and binding competition analyses, revealing that roughly a third of the lineages mapped to the conserved receptor binding region, including potent neutralizing lineages that were confirmed by negative stain electron microscopy to target this region. Additional lineages targeted a protective region on GP2, while others were found to possess cross-filovirus reactivity. Our study advances the understanding of orthomarburgvirus glycoprotein antigenicity and furthers efforts to develop candidate antibody countermeasures against these lethal viruses.

IMPORTANCE
Marburg viruses were the first filoviruses characterized to emerge in humans in 1967 and cause severe hemorrhagic fever with average case fatality rates of ~50%. Although mAb countermeasures have been approved for clinical use against the related Ebola viruses, there are currently no approved countermeasures against Marburg viruses. We successfully isolated a panel of orthomarburgvirus GP-specific mAbs from a macaque immunized with a multivalent combination of filovirus antigens. Our analyses revealed that roughly half of the antibodies in the panel mapped to regions on the glycoprotein shown to protect from infection, including the host cell receptor binding domain and a protective region on the membrane-anchoring subunit. Other antibodies in the panel exhibited broad filovirus GP recognition. Our study describes the discovery of a diverse panel of cross-reactive macaque antibodies targeting orthomarburgvirus and other filovirus GPs and provides candidate immunotherapeutics for further study and development.
Bactericidal effectors of the
Stenotrophomonas maltophilia
type IV secretion system: functional definition of the nuclease TfdA and structural determination of TfcB
Authors: Cobe Brandi L. , Dey Supratim , Minasov George , Inniss Nicole , Satchell Karla J. F. , Cianciotto Nicholas P. 
Published: June 2024

ABSTRACT

Stenotrophomonas maltophilia
expresses a type IV protein secretion system (T4SS) that promotes contact-dependent killing of other bacteria and does so partly by secreting the effector TfcB. Here, we report the structure of TfcB, comprising an N-terminal domain similar to the catalytic domain of glycosyl hydrolase (GH-19) chitinases and a C-terminal domain for recognition and translocation by the T4SS. Utilizing a two-hybrid assay to measure effector interactions with the T4SS coupling protein VirD4, we documented the existence of five more T4SS substrates. One of these was protein 20845, an annotated nuclease. A
S. maltophilia
mutant lacking the gene for 20845 was impaired for killing
Escherichia coli
,
Klebsiella pneumoniae
, and
Pseudomonas aeruginosa
. Moreover, the cloned 20845 gene conferred robust toxicity, with the recombinant
E. coli
being rescued when 20845 was co-expressed with its cognate immunity protein. The 20845 effector was an 899 amino-acid protein, comprised of a GHH-nuclease domain in its N-terminus, a large central region of indeterminant function, and a C-terminus for secretion. Engineered variants of the 20845 gene that had mutations in the predicted catalytic site did not impede
E. coli
, indicating that the antibacterial effect of 20845 involves its nuclease activity. Using flow cytometry with DNA staining, we determined that 20845, but not its mutant variants, confers a loss in DNA content of target bacteria. Database searches revealed that uncharacterized homologs of 20845 occur within a range of bacteria. These data indicate that the
S. maltophilia
T4SS promotes interbacterial competition through the action of multiple toxic effectors, including a potent, novel DNase.

IMPORTANCE

Stenotrophomonas maltophilia
is a multi-drug-resistant, Gram-negative bacterium that is an emerging pathogen of humans. Patients with cystic fibrosis are particularly susceptible to
S. maltophilia
infection. In hospital water systems and various types of infections,
S. maltophilia
co-exists with other bacteria, including other pathogens such as
Pseudomonas aeruginosa
. We previously demonstrated that
S. maltophilia
has a functional VirB/D4 type VI protein secretion system (T4SS) that promotes contact-dependent killing of other bacteria. Since most work on antibacterial systems involves the type VI secretion system, this observation remains noteworthy. Moreover,
S. maltophilia
currently stands alone as a model for a human pathogen expressing an antibacterial T4SS. Using biochemical, genetic, and cell biological approaches, we now report both the discovery of a novel antibacterial nuclease (TfdA) and the first structural determination of a bactericidal T4SS effector (TfcB).
Antimicrobial susceptibility profile and molecular characterization of
Vibrio parahaemolyticus
strains isolated from imported shrimps
Authors: Bourdonnais Erwan , Briet Arnaud , Brauge Thomas , Debuiche Sabine , Helsens Nicolas , Granier Sophie A. , Midelet Graziella 
Published: June 2024

ABSTRACT

Vibrio parahaemolyticus
is a threat to human health and one of the leading bacterial causes of seafood-borne infection worldwide. This pathogen is autochtonous in the marine environment and is able to acquire antimicrobial resistance (AMR) mechanisms, which is a global concern. However, the emergence of AMR
V. parahaemolyticus
strains in seafood is still understudied, as interpretation criteria for this species for antimicrobial susceptibility tests are limited in the literature. In this study, we investigated the susceptibility profiles to clinically important antibiotics and the associated genetic determinants of
V. parahaemolyticus
isolates cultured from imported shrimps. Based on the analysis of the resistance phenotypes of 304
V
.
parahaemolyticus
isolates, we have defined experimental epidemiological cutoff values (CO
WT
) for 14/15 antibiotics tested. We observed that 19.1% of the bacterial isolates had acquired resistance to at least one antibiotic class. The highest number of resistance was associated with tetracycline (14.5% of the strains) and trimethoprim-sulfamethoxazole (3.6%). Moreover, seven strains were multidrug-resistant (MDR, resistant to at least three antibiotic classes). The most frequently identified genes in these strains were
aph(3″)-Ib
/
aph(6)-Id
(aminoglycoside resistance),
sul2
(sulfonamide),
tet(59
) (tetracycline), and
floR
(chloramphenicol). The SXT/R391 family ICE and class 1 integron-integrase genes were detected by PCR in three and one MDR
V. parahaemolyticus
strains, respectively. Consequently,
V. parahaemolyticus
in seafood can act as a reservoir of AMR, constituting a health risk for the consumer.

IMPORTANCE

Our study on “Antimicrobial Resistance Profiles and Genetic Determinants of
Vibrio parahaemolyticus
Isolates from Imported Shrimps” addresses a critical gap in understanding the emergence of antimicrobial resistance (AMR) in this seafood-associated pathogen.
Vibrio parahaemolyticus
is a major cause of global seafood-borne infections, and our research reveals that 19.1% of isolates from imported shrimps display resistance to at least one antibiotic class, with multidrug resistance observed in seven strains. Importantly, we establish experimental epidemiological cutoff values for antibiotic susceptibility, providing valuable criteria specific to
V. parahaemolyticus
. Our findings underscore the potential risk to consumers, emphasizing the need for vigilant monitoring and intervention strategies. This study significantly contributes to the comprehension of AMR dynamics in
V. parahaemolyticus
, offering crucial insights for global public health. The dissemination of our research through Microbiology Spectrum ensures broad accessibility and impact within the scientific community and beyond.
Staff disability data in UK higher education: Evidence from EDI reports
Authors: Saloniki Eirini-Christina , Halvorsrud Kristoffer , Whelan Isabelle , Halim Nishat , George Riya , Orkin Chloe 
Published: June 2024

Objectives
To explore how higher education institutions (HEIs) make transparent the data they collect on staff disability, and how this relates to existing equality, diversity and inclusion (EDI) charters.

Design
Descriptive cross-sector quantitative study based on UK HEIs.

Setting
Higher education sector in the UK.

Participants
162 HEIs across the UK with information extracted from the Higher Education Statistics Agency (HESA), each institution’s website and Advance HE.

Primary and secondary outcome measures
Availability of a publicly available EDI report. Type of information on staff disability identified within the EDI report and level of detail, the latter derived from the number of different types of information provided in the report. Athena SWAN and Disability Confident award level for each HEI were used as a proxy for the sector’s commitment to EDI.

Results
Under a quarter of HEIs do not have an open EDI report online. The majority of Athena SWAN award holders make their EDI reports publicly available, which is similar by Disability Confident status. Russell Group universities are more likely to have a publicly available report. Regionally, EDI report availability is lowest in London. The level of detail with regards to staff disability varies, with more than half of institutions providing ‘little detail’ and just under a third ‘some detail’. Athena SWAN award holders and Disability Confident members are twice as likely to provide ‘some detail’ than those which do not hold an award.

Conclusions
Challenges remain to obtain a clear picture of staff with disabilities within higher education. The lack of both uniformity and transparency in EDI reporting with respect to disability hinders the ability to quantify staff with disabilities within higher education, develop meaningful interventions and address inequities more widely.
Adaptive evolution of Clostridium thermocellum ATCC 27405 on alternate carbon sources leads to altered fermentation profiles
Authors: Daley Steve R. , Kirby Samantha , Sparling Richard 
Published: June 2024

Consolidated bioprocessing candidate, Clostridium thermocellum, is a cellulose hydrolysis specialist, with the ability to ferment the released sugars to produce bioethanol. C. thermocellum is generally studied with model substrates Avicel and cellobiose to understand the metabolic pathway leading to ethanol. In the present study, adaptive laboratory evolution, allowing C. thermocellum DSM 1237 to adapt to growth on glucose, fructose, and sorbitol, with the prospect that some strains will adapt their metabolism to yield more ethanol. Adaptive growth on glucose and sorbitol resulted in an approximately 1 mM and 2 mM increase in ethanol yield per millimolar glucose equivalent, respectively, accompanied by a shift in the production of the other expected fermentation end products. The increase in ethanol yield observed for sorbitol adapted cells was due to the carbon source being more reduced compared to cellobiose. Glucose and cellobiose have similar oxidation states thus the increase in ethanol yield is due to the rerouting of electrons from other reduced metabolic products excluding H2 which did not decrease in yield. There was no increase in ethanol yield observed for fructose adapted cells, but there was an unanticipated elimination of formate production, also observed in sorbitol adapted cells suggesting that fructose has regulatory implications on formate production either at the transcription or protein level.
Horizons that gyre and gimble: a differential characterization of null hypersurfaces
Authors: Blitz Samuel , McNutt David 
Published: June 2024

AbstractMotivated by the thermodynamics of black hole solutions conformal to stationary solutions, we study the geometric invariant theory of null hypersurfaces. It is well-known that a null hypersurface in a Lorentzian manifold can be treated as a Carrollian geometry. Additional structure can be added to this geometry by choosing a connection which yields a Carrollian manifold. In the literature various authors have introduced Koszul connections to study the study the physics on these hypersurfaces. In this paper we examine the various Carrollian geometries and their relationship to null hypersurface embeddings. We specify the geometric data required to construct a rigid Carrollian geometry, and we argue that a connection with torsion is the most natural object to study Carrollian manifolds. We then use this connection to develop a hypersurface calculus suitable for a study of intrinsic and extrinsic differential invariants on embedded null hypersurfaces; motivating examples are given, including geometric invariants preserved under conformal transformations.
On causality violation in different classes of Ricci inverse gravity
Authors: de Souza J. C. R. , Santos A. F. , Ahmed F. 
Published: June 2024

AbstractIn this paper, we investigate a causality-violating four-dimensional space-time, an extension of the two-dimensional Misner space within the framework of modified gravity theories, specifically in the context of Ricci-inverse gravity. To explore this, we focus on two classes of models denoted as $$f({\mathcal {R}}, A^{\mu \nu }\,A_{\mu \nu })$$

f
(
R
,

A

μ
ν

A

μ
ν

)

and $$f({\mathcal {R}}, {\mathcal {A}}, A^{\mu \nu }\,A_{\mu \nu })$$

f
(
R
,
A
,

A

μ
ν

A

μ
ν

)

, and derive the modified field equations using the four-dimensional space-time under consideration. Here, $$A^{\mu \nu }$$

A

μ
ν

is the anti-curvature tensor defined by inverse of the Ricci tensor $$R_{\mu \nu }$$

R

μ
ν

, that is, $$A^{\mu \nu }=R^{-1}_{\mu \nu }$$

A

μ
ν

=

R

μ
ν

-
1

. Additionally, $${\mathcal {A}}$$
A
denotes its scalar, defined as $${\mathcal {A}}=g_{\mu \nu }\,A^{\mu \nu }$$

A
=

g

μ
ν

A

μ
ν

. Our analysis shows that in both models, the modified field equations can be solved by considering the matter energy content as a pure radiation field including the cosmological constant. Furthermore, we demonstrate that the energy density of the pure radiation field and the cosmological constant undergo modifications due to the coupling parameters, and these modifications converge to the results of general relativity when these parameters are set to zero. This observation confirms the possibility of causality violation in the form of closed time-like curves within the framework of Ricci-inverse gravity theory.
A perspective on active glassy dynamics in biological systems
Authors: Sadhukhan Souvik , Dey Subhodeep , Karmakar Smarajit , Nandi Saroj Kumar 
Published: June 2024

AbstractDynamics is central to living systems. Many experiments in the last two decades have revealed glassy dynamics in diverse biological systems, showing a transition between a solid-like and a fluid-like state. The biological systems have nontrivial characteristics: they are active with novel control parameters and immense complexity. Moreover, glassiness in these systems has many nontrivial features, such as the behavior of dynamical heterogeneity and readily found sub-Arrhenius relaxation dynamics. Theoretical treatments of these systems are generally challenging due to their nonequilibrium nature and large number of control parameters. We first discuss the primary characteristics of a glassy system and then review the experiments that started this field and simulations that have led to a deeper understanding. We also show that despite many challenges in these systems, it has been possible to develop theories that have played a significant role in unifying diverse phenomena and bringing insights. The field is at the interface of physics and biology, freely borrowing tools from both disciplines. We first discuss the known equilibrium scenario and then present the primary changes under activity.
CENP-E Inhibition Induces Chromosomal Instability and Synergizes with Diverse Microtubule-Targeting Agents in Breast Cancer
Authors: Tucker John B. , Carlsen Caleb L. , Scribano Christina M. , Pattaswamy Srishrika M. , Burkard Mark E. , Weaver Beth A. 
Published: June 2024

Abstract
Drugs that perturb microtubules are commonly used to treat breast cancers of all subtypes in both early stage and metastatic disease, but they are effective in only approximately 50% of patients. High concentrations of microtubule-targeting agents can elicit mitotic arrest in cell culture models; however, recent evidence from primary and metastatic breast cancers has revealed that these agents only accumulate at intratumoral levels capable of inducing abnormal multipolar mitotic spindles, not mitotic arrest. Although the maintenance of multipolar spindles can generate cytotoxic rates of chromosomal instability (CIN), focusing of aberrant multipolar spindles into normal bipolar spindles can dramatically reduce CIN and confer resistance to microtubule poisons. Here, we showed that inhibition of the mitotic kinesin centromeric-associated protein-E (CENP-E) overcomes resistance caused by focusing multipolar spindles. Clinically relevant microtubule-targeting agents used a mechanistically conserved pathway to induce multipolar spindles without requiring centrosome amplification. Focusing could occur at any point in mitosis, with earlier focusing conferring greater resistance to antimicrotubule agents. CENP-E inhibition increased CIN on focused spindles by generating chromosomes that remained misaligned at spindle poles during anaphase, which substantially increased death in the resulting daughter cells. CENP-E inhibition synergized with diverse, clinically relevant microtubule poisons to potentiate cell death in cell lines and suppress tumor growth in orthotopic tumor models. These results suggest that primary resistance to microtubule-targeting drugs can be overcome by simultaneous inhibition of CENP-E.
Significance: The increased incidence of polar chromosomes induced by inhibition of the mitotic kinesin CENP-E exacerbates chromosomal instability, reduces daughter cell viability, and improves sensitivity to microtubule-targeting therapies.
Object-Oriented Ontology in Shaping Perspective on Bacterial Art and Nonhuman Agency
Authors: Ismail Roslina , Hanafi Amira , Jusoff Kamaruzaman 
Published: June 2024

Abstract
The study of bacterial art provides an opportunity to investigate the philosophical framework of object-oriented ontology (OOO). This viewpoint challenges traditional human-centered perspectives by highlighting the autonomy and agency of all objects, including microorganisms. Objects have their own inherent properties and are regarded as equal actors in the world. The authors highlight the dynamic relationship between humans and microorganisms and the agency of bacteria in bioart. Bacterial art raises concerns regarding control, authorship, aesthetics, and ethics, necessitating interdisciplinary discussions and critical evaluations. This study provides an intriguing case examining the implications of OOO at the intersection of science and art.
Disagreement on the North Atlantic Cold Blob Formation Mechanisms among Climate Models
Authors: Fan Yifei , Chan Duo , Zhang Pengfei , Li Laifang 
Published: June 2024

Abstract
Despite global warming, the sea surface temperature (SST) in the subpolar North Atlantic has decreased since the 1900s. This local cooling, known as the North Atlantic cold blob, signifies a unique role of the subpolar North Atlantic in uptaking heat and hence impacts downstream weather and climate. However, a lack of observational records and their constraints on climate models leave the North Atlantic cold blob formation mechanism inconclusive. Using simulations from phase 6 of Coupled Model Intercomparison Project, we assess the primary processes driving the North Atlantic cold blob within individual models and whether the mechanisms are consistent across models. We show that 11 out of 32 models, which we call “Cold Blob” models, simulate the subpolar North Atlantic cooling over 1900–2014. Further analyzing the heat budget of the subpolar North Atlantic SST shows that models have distinct mechanisms of cold blob formation. While 4 of the 11 Cold Blob models indicate decreased oceanic heat transport convergence (OHTC) as the key mechanism, another four models suggest changes in radiative processes making predominant contributions. The contribution of OHTC and radiative processes is comparable in the remaining three models. Such a model disagreement on the mechanism of cold blob formation may be associated with simulated base-state Atlantic meridional overturning circulation (AMOC) strength, which explains 39% of the intermodel spread in the contribution of OHTC to the simulated cold blob. Models with a stronger base-state AMOC suggest a greater role of OHTC, whereas those with a weaker base-state AMOC indicate that radiative processes are more responsible. This model discrepancy suggests that the cold blob formation mechanism diagnosed from single model should be interpreted with caution.

Significance Statement
The mechanisms driving sea surface temperatures over the subpolar North Atlantic to cool since the 1900s remain uncertain due to the lack of direct observations. Here, we use a temperature change decomposition framework to dissect the historical trend of surface temperature simulated in multiple global climate models. The models diverge on whether the subpolar North Atlantic cooling is induced by reduced ocean heat transport convergence or altered radiative processes. Notably, the importance of ocean heat transport convergence is influenced by the simulated base-state strength of Atlantic meridional overturning circulation and the Irminger Sea’s mixed layer depth. This finding cautions against concluding the cooling mechanism from a single model and highlights a need for ongoing observations to constrain AMOC-related climate projection in the subpolar North Atlantic.