bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Data and Gap Characteristics on the Nonlinear Calculation of Motion During Locomotor Activities
Authors: Mohammadzadeh Gonabadi Arash , Buster Thad W. , Cesar Guilherme M. , Burnfield Judith M. 
Published: June 2024

This study investigated how data series length and gaps in human kinematic data impact the accuracy of Lyapunov exponents (LyE) calculations with and without cubic spline interpolation. Kinematic time series were manipulated to create various data series lengths (28% and 100% of original) and gap durations (0.05–0.20 s). Longer gaps generally resulted in significantly higher LyE% error values in each plane in noninterpolated data. During cubic spline interpolation, only the 0.20-second gap in frontal plane data resulted in a significantly higher LyE% error. Data series length did not significantly affect LyE% error in noninterpolated data. During cubic spline interpolation, sagittal plane LyE% errors were significantly higher at shorter versus longer data series lengths. These findings suggest that not interpolating gaps in data could lead to erroneously high LyE values and mischaracterization of movement variability. When applying cubic spline, a long gap length (0.20 s) in the frontal plane or a short sagittal plane data series length (1000 data points) could also lead to erroneously high LyE values and mischaracterization of movement variability. These insights emphasize the necessity of detailed reporting on gap durations, data series lengths, and interpolation techniques when characterizing human movement variability using LyE values.
Case Commentary: Dual β-lactam as part of regimen to treat
Mycobacterium abscessus
lung disease
Authors: Lippincott Christopher K. , Lamichhane Gyanu 
Published: June 2024

ABSTRACT

Individuals with compromised lung function and immunity are susceptible to developing chronic
Mycobacterium abscessus
infection. Current treatment recommendations typically involve using one β-lactam antibiotic in combination with non-β-lactam antibiotics. However, a recent case study (B. Becken, K. M. Dousa, J. L. Johnson, S. M. Holland, and R. A. Bonomo, Antimicrob Agents Chemother 68:e00319-24, 2024,
https://doi.org/10.1128/aac.00319-24
) demonstrated successful treatment of chronic
M. abscessus
lung disease in a child using two β-lactam antibiotics simultaneously. This commentary reviews the emerging evidence and outstanding questions regarding dual β-lactam therapy for
M. abscessus
infections.
The catabolism of ethylene glycol by
Rhodococcus jostii
RHA1 and its dependence on mycofactocin
Authors: Roccor Raphael , Wolf Megan E. , Liu Jie , Eltis Lindsay D. 
Published: June 2024

ABSTRACT

Ethylene glycol (EG) is a widely used industrial chemical with manifold applications and also generated in the degradation of plastics such as polyethylene terephthalate.
Rhodococcus jostii
RHA1 (RHA1), a potential biocatalytic chassis, grows on EG. Transcriptomic analyses revealed four clusters of genes potentially involved in EG catabolism: the
mad
locus, predicted to encode
m
ycofactocin-dependent
a
lcohol
d
egradation, including the catabolism of EG to glycolate; two GCL clusters, predicted to encode glycolate and glyoxylate catabolism; and the
mft
genes, predicted to specify mycofactocin biosynthesis. Bioinformatic analyses further revealed that the
mad
and
mft
genes are widely distributed in mycolic acid-producing bacteria such as RHA1. Neither Δ
madA
nor Δ
mftC
RHA1 mutant strains grew on EG but grew on acetate. In resting cell assays, the Δ
madA
mutant depleted glycolaldehyde but not EG from culture media. These results indicate that
madA
encodes a mycofactocin-dependent alcohol dehydrogenase that initiates EG catabolism. In contrast to some mycobacterial strains, the
mad
genes did not appear to enable RHA1 to grow on methanol as sole substrate. Finally, a strain of RHA1 adapted to grow ~3× faster on EG contained an overexpressed gene,
aldA2
, predicted to encode an aldehyde dehydrogenase. When incubated with EG, this strain accumulated lower concentrations of glycolaldehyde than RHA1. Moreover, ecotopically expressed
aldA2
increased RHA1’s tolerance for EG further suggesting that glycolaldehyde accumulation limits growth of RHA1 on EG. Overall, this study provides insights into the bacterial catabolism of small alcohols and aldehydes and facilitates the engineering of
Rhodococcus
for the upgrading of plastic waste streams.

IMPORTANCE

Ethylene glycol (EG), a two-carbon (C2) alcohol, is produced in high volumes for use in a wide variety of applications. There is burgeoning interest in understanding and engineering the bacterial catabolism of EG, in part to establish circular economic routes for its use. This study identifies an EG catabolic pathway in
Rhodococcus
, a genus of bacteria well suited for biocatalysis. This pathway is responsible for the catabolism of methanol, a C1 feedstock, in related bacteria. Finally, we describe strategies to increase the rate of degradation of EG by increasing the transformation of glycolaldehyde, a toxic metabolic intermediate. This work advances the development of biocatalytic strategies to transform C2 feedstocks.
Lamotrigine-mediated rescue of RsgA-deficient
Escherichia coli
reveals another role of IF2 in ribosome biogenesis
Authors: Singh Sudhir , Singh Jitendra , Varshney Umesh 
Published: June 2024

ABSTRACT

RsgA (small ribosomal subunit, 30S, GTPase), a late-stage biogenesis factor, releases RbfA from 30S-RbfA complex.
Escherichia coli
Δ
rsgA
(deleted for
rsgA
) shows a slow growth phenotype and an increased accumulation of 17S rRNA (precursor of 16S rRNA) and the ribosomal subunits. Here, we show that the rescue of the Δ
rsgA
strain by multicopy
infB
(IF2) is enhanced by simultaneous overexpression of initiator tRNA (i-tRNA), suggesting a role of initiation complex formation in growth rescue. The synergistic effect of IF2/i-tRNA is accompanied by increased processing of 17S rRNA (to 16S), and protection of the 16S rRNA 3′-minor domain. Importantly, we show that an IF2-binding anticonvulsant drug, lamotrigine (Ltg), also rescues the Δ
rsgA
strain growth. The rescue is accompanied by increased processing of 17S rRNA, protection of the 3′-minor domain of 16S rRNA, and increased 70S ribosomes in polysome profiles. However, Ltg becomes inhibitory to the
ΔrsgA
strain whose growth was already rescued by an L83R mutation in
rbfA
. Interestingly, like wild-type
infB
, overproduction of Ltg
R
infB
alleles (having indel mutations in their domain II) also rescues the Δ
rsgA
strain (independent of Ltg). Our observations suggest the dual role of IF2 in rescuing the Δ
rsgA
strain. First, together with i-tRNA, IF2 facilitates the final steps of processing of 17S rRNA. Second, a conformer of IF2 functionally compensates for RsgA, albeit poorly, during 30S biogenesis.

IMPORTANCE

RsgA is a late-stage ribosome biogenesis factor. Earlier,
infB
(IF2) was isolated as a multicopy suppressor of the
Escherichia coli
Δ
rsgA
strain. How IF2 rescued the strain growth remained unclear. This study reveals that (i) the multicopy
infB
-mediated growth rescue of
E. coli
Δ
rsgA
and the processing of 17S precursor to 16S rRNA in the strain are enhanced upon simultaneous overexpression of initiator tRNA and (ii) a conformer of IF2, whose occurrence increases when IF2 is overproduced or when
E. coli
Δ
rsgA
is treated with Ltg (an anticonvulsant drug that binds to domain II of IF2), compensates for the function of RsgA. Thus, this study reveals yet another role of IF2 in ribosome biogenesis.
Interferon-γ inducible factor 16 (IFI16) restricts adeno-associated virus type 2 (AAV2) transduction in an immune-modulatory independent way
Authors: Sutter Sereina O. , Tobler Kurt , Seyffert Michael , Lkharrazi Anouk , Zöllig Joël , Schraner Elisabeth M. , Vogt Bernd , Büning Hildegard , Fraefel Cornel 
Published: June 2024

ABSTRACT

We determined the transcription profile of adeno-associated virus type 2 (AAV2)-infected primary human fibroblasts. Subsequent analysis revealed that cells respond to AAV infection through changes in several significantly affected pathways, including cell cycle regulation, chromatin modulation, and innate immune responses. Various assays were performed to validate selected differentially expressed genes and to confirm not only the quality but also the robustness of the raw data. One of the genes upregulated in AAV2-infected cells was interferon-γ inducible factor 16 (IFI16). IFI16 is known as a multifunctional cytosolic and nuclear innate immune sensor for double-stranded as well as single-stranded DNA, exerting its effects through various mechanisms, such as interferon response, epigenetic modifications, or transcriptional regulation. IFI16 thereby constitutes a restriction factor for many different viruses among them, as shown here, AAV2 and thereof derived vectors. Indeed, the post-transcriptional silencing of
IFI16
significantly increased AAV2 transduction efficiency, independent of the structure of the virus/vector genome. We also show that IFI16 exerts its inhibitory effect on AAV2 transduction in an immune-modulatory independent way by interfering with Sp1-dependent transactivation of wild-type AAV2 and AAV2 vector promoters.

IMPORTANCE
Adeno-associated virus (AAV) vectors are among the most frequently used viral vectors for gene therapy. The lack of pathogenicity of the parental virus, the long-term persistence as episomes in non-proliferating cells, and the availability of a variety of AAV serotypes differing in their cellular tropism are advantageous features of this biological nanoparticle. To deepen our understanding of virus-host interactions, especially in terms of antiviral responses, we present here the first transcriptome analysis of AAV serotype 2 (AAV2)-infected human primary fibroblasts. Our findings indicate that interferon-γ inducible factor 16 acts as an antiviral factor in AAV2 infection and AAV2 vector-mediated cell transduction in an immune-modulatory independent way by interrupting the Sp1-dependent gene expression from viral or vector genomes.
An efficient
trans
complementation system for
in vivo
replication of defective poliovirus mutants
Authors: Arita Minetaro 
Published: June 2024

ABSTRACT

The picornavirus genome encodes a large, single polyprotein that is processed by viral proteases to form an active replication complex. The replication complex is formed with the viral genome, host proteins, and viral proteins that are produced/translated directly from each of the viral genomes (viral proteins provided in
cis
). Efficient complementation
in vivo
of replication complex formation by viral proteins provided in
trans
, thus exogenous or ectopically expressed viral proteins, remains to be demonstrated. Here, we report an efficient
trans
complementation system for the replication of defective poliovirus (PV) mutants by a viral polyprotein precursor in HEK293 cells. Viral 3AB in the polyprotein, but not 2BC, was processed exclusively in
cis
. Replication of a defective PV replicon mutant, with a disrupted cleavage site for viral 3C
pro
protease between 3C
pro
and 3D
pol
(3C/D[A/G] mutant) could be rescued by a viral polyprotein provided in
trans
. Only a defect of 3D
pol
activity of the replicon could be rescued in
trans
; inactivating mutations in 2C
ATPase/hel
, 3B, and 3C
pro
of the replicon completely abrogated the
trans
-rescued replication. An intact N-terminus of the 3C
pro
domain of the 3CD
pro
provided in
trans
was essential for the
trans
-active function. By using this
trans
complementation system, a high-titer defective PV pseudovirus (PV
pv
) (>10
7
infectious units per mL) could be produced with the defective mutants, whose replication was completely dependent on
trans
complementation. This work reveals potential roles of exogenous viral proteins in PV replication and offers insights into protein/protein interaction during picornavirus infection.

IMPORTANCE

Viral polyprotein processing is an elaborately controlled step by viral proteases encoded in the polyprotein; fully processed proteins and processing intermediates need to be correctly produced for replication, which can be detrimentally affected even by a small modification of the polyprotein. Purified/isolated viral proteins can retain their enzymatic activities required for viral replication, such as protease, helicase, polymerase, etc. However, when these proteins of picornavirus are exogenously provided (provided in
trans
) to the viral replication complex with a defective viral genome, replication is generally not rescued/complemented, suggesting the importance of viral proteins endogenously provided (provided in
cis
) to the replication complex. In this study, I discovered that only the viral polymerase activity of poliovirus (PV) (the typical member of picornavirus family) could be efficiently rescued by exogenously expressed viral proteins. The current study reveals potential roles for exogenous viral proteins in viral replication and offers insights into interactions during picornavirus infection.
Shotgun metagenomic sequencing of swab samples from Japanese university campuses
Authors: Tsujimoto Megumu , Dewi Dewa A. P. Rasmika , Mason Christopher E. , Shiwa Yuh , Suzuki Haruo 
Published: June 2024

ABSTRACT

We obtained shotgun metagenome sequences from swab samples obtained through 3-minute swabbing of different surfaces and the air within buildings at three university campuses in part of the Greater Tokyo Area in Japan. These data aid in understanding built environment microbial communities and elucidate various microbial profiles across different locations.
Exploring the potential of isorhapontigenin: attenuating
Staphylococcus aureus
virulence through MgrA-mediated regulation
Authors: Yuan Lei , Xi Huimin , Luo Zhaoxia , Liu Mei-fang , Chen Qiang , Zhu Qing , Zhao Rui , Sheng Yi-yun 
Published: June 2024

ABSTRACT

The emerging prevalence of drug-resistant
Staphylococcus aureus
isolates underscores the urgent need for alternative therapeutic strategies due to the declining effectiveness of traditional antibiotics in clinical settings. MgrA, a key virulence regulator in
S. aureus
, orchestrates the expression of numerous virulence factors. Here, we report the discovery of isorhapontigenin, a methoxylated analog of resveratrol, as a potential anti-virulence agent against
S. aureus
. Isorhapontigenin effectively inhibits the hemolytic activity of
S. aureus
in a non-bactericidal manner. Additionally, it significantly reduces the cytotoxicity of
S. aureus
and impairs its ability to survive in macrophages. Mechanistically, isorhapontigenin modulates the expression of virulence factors, dose-dependently downregulating
hla
and upregulating the MgrA-regulated gene
spa
. Electrophoretic mobility shift assays demonstrated that isorhapontigenin inhibits the binding of MgrA to the
hla
promoter in a dose-dependent manner. Thermal shift assays confirmed the direct interaction between isorhapontigenin and the MgrA protein. The
in vivo
experiments demonstrated that isorhapontigenin significantly reduced the area of skin abscesses and improved survival in a pneumonia model while decreasing bacterial burden and inflammation in the lungs. In conclusion, isorhapontigenin holds potential as a candidate drug for further development as an anti-virulence agent for treating
S. aureus
infections.

IMPORTANCE

The emergence of antibiotic-resistant
Staphylococcus aureus
strains presents a formidable challenge to public health, necessitating novel approaches in combating these pathogens. Traditional antibiotics are becoming increasingly ineffective, leading to a pressing need for innovative therapeutic strategies. In this study, targeting virulence factors that play a crucial role in the pathogenesis of bacterial infections offers a promising alternative to circumvent resistance mechanisms. The discovery of isorhapontigenin as an inhibitor of
S. aureus
virulence represents a significant advance in anti-virulence therapy.
Expanded trade: tripartite interactions in the mycorrhizosphere
Authors: Charakas Christos , Khokhani Devanshi 
Published: June 2024

ABSTRACT

Interactions between arbuscular mycorrhizal fungi (AMF), plants, and the soil microbial community have the potential to increase the availability and uptake of phosphorus (P) and nitrogen (N) in agricultural systems. Nutrient exchange between plant roots, AMF, and the adjacent soil microbes occurs at the interface between roots colonized by mycorrhizal fungi and soil, referred to as the mycorrhizosphere. Research on the P exchange focuses on plant–AMF or AMF–microbe interactions, lacking a holistic view of P exchange between the plants, AMF, and other microbes. Recently, N exchange at both interfaces revealed the synergistic role of AMF and bacterial community in N uptake by the host plant. Here, we highlight work carried out on each interface and build upon it by emphasizing research involving all members of the tripartite network. Both nutrient systems are challenging to study due to the complex chemical and biological nature of the mycorrhizosphere. We discuss some of the effective methods to identify important nutrient processes and the tripartite members involved in these processes. The extrapolation of
in vitro
studies into the field is often fraught with contradiction and noise. Therefore, we also suggest some approaches that can potentially bridge the gap between laboratory-generated data and their extrapolation to the field, improving the applicability and contextual relevance of data within the field of mycorrhizosphere interactions. Overall, we argue that the research community needs to adopt a holistic tripartite approach and that we have the means to increase the applicability and accuracy of
in vitro
data in the field.
Isoforms of the Cytoskeletal LIM-Domain Protein Zyxin in the Early Embryogenesis of Xenopus laevis
Authors: Ivanova E. D. , Parshina E. A. , Zaraisky A. G. , Martynova N. Y. 
Published: June 2024

Abstract
Objective: The study of highly conserved mechanosensitive proteins, such as zyxin, is essential due to their role in shaping embryos of all animals during embryogenesis through coordinated morphogenetic processes and controlled cell differentiation. This study aims to identify endogenous zyxin isoforms in Xenopus laevis and investigate changes in their abundance and intracellular localization during embryogenesis. Methods: Endogenous proteins were primarily detected using specific antibodies. Polyclonal antibodies targeting the C-terminal region of zyxin containing the NES and three LIM domains (438–663 aa), as well as antibodies against the N-terminal proline-rich region of Zyxin (1–373 aa) crucial for interactions with actinin and cytoskeletal proteins, were employed. Western blotting with these antibodies was conducted on Xenopus laevis embryo cell samples after fractionation into nuclear and cytoplasmic fractions. Results and Discussion: The study revealed multiple isoforms of zyxin in Xenopus laevis, including a full-length modified protein (105 kDa), an unmodified form (70 kDa), and two truncated forms of 45 and 37 kDa. The number and subcellular distribution of the truncated forms were found to vary based on the developmental stage, with increased levels of the 45 and 37 kDa isoforms observed in the early stages. Conclusions: This work provides novel insights into changes in the abundance and localization of zyxin isoforms during embryonic development, shedding light on the dynamics of this mechanosensitive protein in the embryo.
A New Protein Glosaxin Composed of Noncatalytic Domains of Class PIII Metalloproteinase from the Pit Viper Gloydius saxatilis Venom Inhibits Nicotinic Acetylcholine Receptor
Authors: Osipov A. V. , Kryukova E. V. , Ojomoko L. O. , Shelukhina I. V. , Ziganshin R. H. , Starkov V. G. , Andreeva T. V. , Tsetlin V. I. , Utkin Yu. N. 
Published: June 2024

Abstract
Objective: Although main components of the venoms from Viperidae snakes are hemotoxins, several studies indicate the presence of neurotoxins in these venoms. We previously found that the venom of pit viper Gloydius saxatilis inhibited the muscle-type nicotinic acetylcholine receptor (nAChR). The objective of present work is to isolate and characterize a neurotoxic protein from this venom. Methods: The protein was isolated by liquid chromatography and characterized using high resolution mass-spectrometry. Results and Discussion: The isolated protein called glosaxin inhibited the binding of the α-bungarotoxin to the nAChR of muscle type from Torpedo californica. Investigation of the amino acid sequence of the isolated protein by high resolution mass spectrometry and the subsequent bioinformatic analysis showed that it is homologous to the amino acid sequences of disintegrin-like proteins, consisting of non-catalytic domains of class PIII metalloproteinases from the venom of pit vipers of genus Gloydius. Glosaxin was shown to inhibit the binding of α-bungarotoxin to T. californica nAChR with IC50 = 51 μM. It also inhibited ACh-induced functional responses of the human neuronal nAChR of α3β2 subtype. Conclusions: This is the first evidence for the ability of proteins consisting of non-catalytic domains of snake venom class PIII metalloproteinase to inhibit the nAChR.
Digital ray: enhancing cataractous fundus images using style transfer generative adversarial networks to improve retinopathy detection
Authors: Liu Lixue , Hong Jiaming , Wu Yuxuan , Liu Shaopeng , Wang Kai , Li Mingyuan , Zhao Lanqin , Liu Zhenzhen , Li Longhui , Cui Tingxin , Tsui Ching-Kit , Xu Fabao , Hu Weiling , Yun Dongyuan , Chen Xi , Shang Yuanjun , Bi Shaowei , Wei Xiaoyue , Lai Yunxi , Lin Duoru , Fu Zhe , Deng Yaru , Cai Kaimin , Xie Yi , Cao Zizheng , Wang Dongni , Zhang Xulin , Dongye Meimei , Lin Haotian , Wu Xiaohang 
Published: June 2024

Background/aimsThe aim of this study was to develop and evaluate digital ray, based on preoperative and postoperative image pairs using style transfer generative adversarial networks (GANs), to enhance cataractous fundus images for improved retinopathy detection.MethodsFor eligible cataract patients, preoperative and postoperative colour fundus photographs (CFP) and ultra-wide field (UWF) images were captured. Then, both the original CycleGAN and a modified CycleGAN (C2ycleGAN) framework were adopted for image generation and quantitatively compared using Frechet Inception Distance (FID) and Kernel Inception Distance (KID). Additionally, CFP and UWF images from another cataract cohort were used to test model performances. Different panels of ophthalmologists evaluated the quality, authenticity and diagnostic efficacy of the generated images.ResultsA total of 959 CFP and 1009 UWF image pairs were included in model development. FID and KID indicated that images generated by C2ycleGAN presented significantly improved quality. Based on ophthalmologists’ average ratings, the percentages of inadequate-quality images decreased from 32% to 18.8% for CFP, and from 18.7% to 14.7% for UWF. Only 24.8% and 13.8% of generated CFP and UWF images could be recognised as synthetic. The accuracy of retinopathy detection significantly increased from 78% to 91% for CFP and from 91% to 93% for UWF. For retinopathy subtype diagnosis, the accuracies also increased from 87%–94% to 91%–100% for CFP and from 87%–95% to 93%–97% for UWF.ConclusionDigital ray could generate realistic postoperative CFP and UWF images with enhanced quality and accuracy for overall detection and subtype diagnosis of retinopathies, especially for CFP.\Trial registration numberThis study was registered with ClinicalTrials.gov (NCT05491798).