bluuebunny/crossref_metadata_2025 huggingface dataset:
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Authors: Biehler Michael , Mock Reinaldo , Kode Shriyanshu , Mehmood Maham , Bhardwaj Palin , Shi Jianjun
Published: October 2023

Additive manufacturing (AM) has revolutionized the way we design, prototype, and produce complex parts with unprecedented geometries. However, the lack of understanding of the functional properties of 3D-printed parts has hindered their adoption in critical applications where reliability and durability are paramount. This paper proposes a novel approach to the functional qualification of 3D-printed parts via physical and digital twins. Physical twins are parts that are printed under the same process conditions as the functional parts and undergo a wide range of (destructive) tests to determine their mechanical, thermal, and chemical properties. Digital twins are virtual replicas of the physical twins that are generated using finite element analysis (FEA) simulations based on the 3D shape of the part of interest. We propose a novel approach to transfer learning, specifically designed for the fusion of diverse, unstructured 3D shape data and process inputs from multiple sources. The proposed approach has demonstrated remarkable results in predicting the functional properties of 3D-printed lattice structures. From an engineering standpoint, this paper introduces a comprehensive and innovative methodology for the functional qualification of 3D-printed parts. By combining the strengths of physical and digital twins with transfer learning, our approach opens up possibilities for the widespread adoption of 3D printing in safety-critical applications. Methodologically, this work presents a significant advancement in transfer learning techniques, specifically addressing the challenges of multi-source (e.g., digital and physical twins) and multi-input (e.g., 3D shapes and process variables) transfer learning.
Wear and corrosion resistance of zinc-oxide and zirconium-oxide coated WE43 magnesium alloy
Authors: Gül Canser , Durmuş Hülya , Albayrak Sevda , Çömez Nilay
Published: October 2023

Magnesium alloy, which draws attention with its lightness and high specific strength, is frequently preferred due to its advantages. However, it is necessary to improve the wear and corrosion properties in order to develop the areas of use in the automotive, aircraft, and space industries. For this purpose, after the surface preparation of the main material WE43 Mg alloy, ZnO and ZrO2 coatings were made and characterized in this study. The surface morphology and structural and chemical properties of the samples were investigated using profilometry, contact angle tests, scanning electron microscopy, and x-ray diffraction. Corrosion tests have been carried out. In order to determine the wear performance of the samples, the wear-related volume losses were measured and the friction coefficients were compared. Layers with 2–6 μm coating thickness were obtained homogeneously on the polished and sandblasted sample surfaces. It was determined that the coating layers grew in the form of columns and did not contain capillary cracks. As a result of the study, it was observed that the ZnO-coated samples had the highest wear and corrosion resistance, and the wear and corrosion resistance of the coatings and magnesium alloy substrates improved.
Evaluation of Physical Activity Assessment Using a Triaxial Activity Monitor in Community-Dwelling Older Japanese Adults With and Without Lifestyle-Related Diseases
Authors: Nagayoshi Sho , Yatsugi Harukaze , Liu Xin , Saito Takafumi , Yamatsu Koji , Kishimoto Hiro
Published: October 2023

Background: Several previous studies investigated physical activity of older adults using wearable devices, but more studies need to develop normative values for chronic disease conditions. This study aimed to investigate physical activity using a triaxial activity monitor in community-dwelling older Japanese adults with and without lifestyle-related diseases. Methods: Data from a total of 732 community-dwelling older Japanese men and women were collected and analyzed in a cross-sectional study. The participants’ physical activity was assessed for seven consecutive days by a triaxial accelerometer. Physical activity was assessed by number of lifestyle-related diseases and six lifestyle-related diseases categories by gender. Physical activity was assessed separately for total, locomotive, and nonlocomotive physical activity. Results: Participants with multiple (two or more) diseases had significantly lower total light-intensity physical activity (LPA; 278.5 ± 8.4 min/day) and nonlocomotive LPA (226.4 ± 7.0 min/day) versus without diseases in men. Compared in each disease category, total LPA and nonlocomotive LPA was significantly lower in men with hypertension and diabetes. Total sedentary time was significantly higher in men with hypertension, diabetes, and heart disease. Locomotive LPA was significantly lower in men with diabetes. In women, locomotive moderate- to vigorous-intensity physical activity was significantly higher in women with diabetes, and nonlocomotive moderate- to vigorous-intensity physical activity was significantly lower in women with heart disease. Conclusion: This study demonstrated that older Japanese men with multiple lifestyle-related diseases had lower physical activity. In each disease category, hypertension, diabetes, and heart disease affected lower physical activity, especially in men.
Echocardiographic Parameters Associated With Cardiorespiratory Fitness and Physical Activity in Childhood Acute Lymphoblastic Leukemia Survivors
Authors: Caru Maxime , Dubois Pierre , Curnier Daniel , Andelfinger Gregor , Krajinovic Maja , Laverdière Caroline , Sinnett Daniel , Périé Delphine
Published: October 2023

Background: Children’s exposure to chemotherapeutic agents causes several long-term adverse effects but physical activity has been evidenced to be an effective strategy to improve cardiac function. This cross-sectional study aimed to explore the association between physical activity levels, cardiorespiratory fitness, and cardiac parameters measured by echocardiography. Methods: Participants were 216n childhood acute lymphoblastic leukemia survivors who underwent a maximal cardiopulmonary exercise test and self-reported their daily minutes of moderate to vigorous physical activity. They underwent a complete transthoracic echocardiographic assessment. Systolic and diastolic function analysis and strain images analysis were performed. The associations were studied through the preventive fraction (examined with univariate crude and adjusted logistic regression models) of regular physical activity (≥150 min·wk−1) and adequate cardiorespiratory fitness levels (above the median ≥ 32.0 mL·kg−1·min−1) on cardiac parameters. Results: Crude analysis shows that regular physical activity was associated with a significant preventive fraction in mitral E/A ratio (56%; P = .013), while adjusted analyses highlighted a nonsignificant reduction of 74% to 37% in the prevalence of cardiac parameters associated with physical activity. Similar associations of adequate cardiorespiratory fitness on cardiac parameters were observed. Adjusted analyses revealed a nonsignificant reduction of 7% to 86% in the prevalence of cardiac parameters associated with cardiorespiratory fitness. Conclusion: This study reports that regular physical activity and adequate cardiorespiratory fitness were associated with a higher preventive fraction. Thus, engaging in physical activity prevents childhood acute lymphoblastic leukemia survivors’ cardiac dysfunctions. These findings are novel and clinically relevant in pediatric cardiooncology and provide additional evidence to strengthen the benefits of exercise as long-term care in childhood cancer survivors.
Shaping Policy and Practice: Analyzing the Reach of Highly Cited and High Altmetrics Publications for Broader Impact on Physical Activity
Authors: Ramírez Varela Andrea , Serrano Natalicio , Mejía Grueso Juliana , Nguyen Anita , Salvo Deborah , Brownson Ross C. , Bauman Adrian , Reis Rodrigo , Hallal Pedro , Pratt Michael
Published: October 2023

Background: A significant gap remains between the availability of physical activity (PA) evidence-based interventions and their application in real-world settings in policy and practice areas. This study aims to describe highly cited and high altmetrics publications in PA research and explore their impact on PA policy and practice. Methods: Mixed-methods sequential explanatory study including the identification and description of the top highly cited and high altmetrics PA publications from the last 10 years (including study design, population, type of PA study, number of citations, and altmetrics score), and interviews with key informants regarding research dissemination and implications on PA policy and practice. Results: When considering publication type, the most frequent highly cited publications were health consequences (40%, altmetrics = 42%), measurement/trends (23%, altmetrics = 10%), and correlates/determinants (21%, altmetrics = 26%) studies. They were predominantly cross-sectional (50%, altmetrics = 28%), systematic reviews (38%, altmetrics = 18%), and longitudinal studies (8%, altmetrics = 37%). All authors who participated in the interviews agreed that the most important factors in disseminating findings and influencing PA policy and practice were the published peer-reviewed manuscript itself, the reputation of the journal, the communication strategy, and the use of online platforms. Conclusions: To have a real-world influence on PA policy and practice, it is not enough to publish the results in scientific journals and participate in media outreach. To successfully involve policymakers and communities in appropriating the evidence and evaluating the extent to which these findings affect policy and practice outcomes, it is critical to lead co-creation, co-dissemination, advocacy, and capacity building efforts.
Recognition of polymorphic Csd proteins determines sex in the honeybee
Authors: Otte Marianne , Netschitailo Oksana , Weidtkamp-Peters Stefanie , Seidel Claus A. M. , Beye Martin
Published: October 2023

Sex in honeybees,
Apis mellifera
, is genetically determined by heterozygous versus homo/hemizygous genotypes involving numerous alleles at the single complementary sex determination locus. The molecular mechanism of sex determination is however unknown because there are more than 4950 known possible allele combinations, but only two sexes in the species. We show how protein variants expressed from complementary sex determiner (
csd
) gene determine sex. In females, the amino acid differences between Csd variants at the potential-specifying domain (PSD) direct the selection of a conserved coiled-coil domain for binding and protein complexation. This recognition mechanism activates Csd proteins and, thus, the female pathway. In males, the absence of polymorphisms establishes other binding elements at PSD for binding and complexation of identical Csd proteins. This second recognition mechanism inactivates Csd proteins and commits male development via default pathway. Our results demonstrate that the recognition of different versus identical variants of a single protein is a mechanism to determine sex.
Insights into dynamics and gating properties of T2SS secretins
Authors: Barbat Brice , Douzi Badreddine , Ball Geneviève , Tribout Mathilde , El Karkouri Khalid , Kellenberger Christine , Voulhoux Romé
Published: October 2023

Secretins are outer membrane (OM) channels found in various bacterial nanomachines that secrete or assemble large extracellular structures. High-resolution 3D structures of type 2 secretion system (T2SS) secretins revealed bimodular channels with a C-module, holding a conserved central gate and an optional top gate, followed by an N-module for which multiple structural organizations have been proposed. Here, we perform a structure-driven in vivo study of the XcpD secretin, which validates one of the organizations of the N-module whose flexibility enables alternative conformations. We also show the existence of the central gate in vivo and its required flexibility, which is key for substrate passage and watertightness control. Last, functional, genomic, and phylogenetic analyses indicate that the optional top gate provides a gain of watertightness. Our data illustrate how the gating properties of T2SS secretins allow these large channels to overcome the duality between the necessity of preserving the OM impermeability while simultaneously promoting the secretion of large, folded effectors.
Low-temperature 3D printing of transparent silica glass microstructures
Authors: Li Mingzhe , Yue Liang , Rajan Arunkumar Chitteth , Yu Luxia , Sahu Harikrishna , Montgomery S. Macrae , Ramprasad Rampi , Qi H. Jerry
Published: October 2023

Transparent silica glass is one of the most essential materials used in society and industry, owing to its exceptional optical, thermal, and chemical properties. However, glass is extremely difficult to shape, especially into complex and miniaturized structures. Recent advances in three-dimensional (3D) printing have allowed for the creation of glass structures, but these methods involve time-consuming and high-temperature processes. Here, we report a photochemistry-based strategy for making glass structures of micrometer size under mild conditions. Our technique uses a photocurable polydimethylsiloxane resin that is 3D printed into complex structures and converted to silica glass via deep ultraviolet (DUV) irradiation in an ozone environment. The unique DUV-ozone conversion process for silica microstructures is low temperature (~220°C) and fast (<5 hours). The printed silica glass is highly transparent with smooth surface, comparable to commercial fused silica glass. This work enables the creation of arbitrary structures in silica glass through photochemistry and opens opportunities in unexplored territories for glass processing techniques.
Modeling early warning signs of possible Amazon Forest dieback
Authors: Spracklen D. V. , Coelho C. A. S.
Published: October 2023

Deforestation of the Amazon may reach a critical point where abrupt declines in rainfall could cause widespread forest dieback.
A protein-free vaccine stimulates innate immunity and protects against nosocomial pathogens
Authors: Yan Jun , Nielsen Travis B. , Lu Peggy , Talyansky Yuli , Slarve Matt , Reza Hernan , Novakovic Boris , Netea Mihai G. , Keller Ashley E. , Warren Troy , DiGiandomenico Antonio , Sellman Bret R. , Luna Brian M. , Spellberg Brad
Published: October 2023

Traditional vaccines are difficult to deploy against the diverse antimicrobial-resistant, nosocomial pathogens that cause health care–associated infections. We developed a protein-free vaccine composed of aluminum hydroxide, monophosphoryl lipid A, and fungal mannan that improved survival and reduced bacterial burden of mice with invasive blood or lung infections caused by methicillin-resistant
Staphylococcus aureus
, vancomycin-resistant
Enterococcus faecalis
, extended-spectrum beta-lactamase–expressing
Escherichia coli
, and carbapenem-resistant strains of
Acinetobacter baumannii
,
Klebsiella pneumoniae
, and
Pseudomonas aeruginosa.
The vaccine also conferred protection against the fungi
Rhizopus delemar
and
Candida albicans
. Efficacy was apparent by 24 hours and lasted for up to 28 days after a single vaccine dose, with a second dose restoring efficacy. The vaccine acted through stimulation of the innate, rather than the adaptive, immune system, as demonstrated by efficacy in the absence of lymphocytes that were abrogated by macrophage depletion. A role for macrophages was further supported by the finding that vaccination induced macrophage epigenetic alterations that modulated phagocytosis and the inflammatory response to infection. Together, these data show that this protein-free vaccine is a promising strategy to prevent deadly antimicrobial-resistant health care–associated infections.
An mpox virus mRNA-lipid nanoparticle vaccine confers protection against lethal orthopoxviral challenge
Authors: Freyn Alec W. , Atyeo Caroline , Earl Patricia L. , Americo Jeffrey L. , Chuang Gwo-Yu , Natarajan Harini , Frey Tiffany R. , Gall Jason G. , Moliva Juan I. , Hunegnaw Ruth , Asthagiri Arunkumar Guha , Ogega Clinton O. , Nasir Arshan , Santos Genesis , Levin Rafael H. , Meni Anusha , Jorquera Patricia A. , Bennett Hamilton , Johnson Joshua A. , Durney Michael A. , Stewart-Jones Guillaume , Hooper Jay W. , Colpitts Tonya M. , Alter Galit , Sullivan Nancy J. , Carfi Andrea , Moss Bernard
Published: October 2023

Mpox virus (MPXV) caused a global outbreak in 2022. Although smallpox vaccines were rapidly deployed to curb spread and disease among those at highest risk, breakthrough disease was noted after complete immunization. Given the threat of additional zoonotic events and the virus’s evolving ability to drive human-to-human transmission, there is an urgent need for an MPXV-specific vaccine that confers protection against evolving MPXV strains and related orthopoxviruses. Here, we demonstrate that an mRNA-lipid nanoparticle vaccine encoding a set of four highly conserved MPXV surface proteins involved in virus attachment, entry, and transmission can induce MPXV-specific immunity and heterologous protection against a lethal vaccinia virus (VACV) challenge. Compared with modified vaccinia virus Ankara (MVA), which forms the basis for the current MPXV vaccine, immunization with an mRNA-based MPXV vaccine generated superior neutralizing activity against MPXV and VACV and more efficiently inhibited spread between cells. We also observed greater Fc effector T
H
1-biased humoral immunity to the four MPXV antigens encoded by the vaccine, as well as to the four VACV homologs. Single MPXV antigen–encoding mRNA vaccines provided partial protection against VACV challenge, whereas multivalent vaccines combining mRNAs encoding two, three, or four MPXV antigens protected against disease-related weight loss and death equal or superior to MVA vaccination. These data demonstrate that an mRNA-based MPXV vaccine confers robust protection against VACV.
Antimicrobial effects of Medicines for Malaria Venture Pathogen Box compounds on strains of
Neisseria gonorrhoeae
Authors: Mensah Eric , Fourie P. Bernard , Peters Remco P. H.
Published: October 2023

Therapeutic options for
Neisseria gonorrhoeae
are limited due to emerging global resistance. New agents and treatment options to treat patients with susceptible and multi-extensively drug-resistant
N. gonorrhoeae
is a high priority. This study used an
in vitro
approach to explore the antimicrobial potential, as well as synergistic effects of Medicine for Malaria Venture (MMV) Pathogen Box compounds against ATCC and clinical
N. gonorrhoeae
strains. Microbroth dilution assay was used to determine pathogen-specific minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the Pathogen Box compounds against susceptible and resistant
N. gonorrhoeae
strains, with modification, by adding PrestoBlue HS Cell Viability Reagent. A checkerboard assay was used to determine synergy between the active compounds and in conjunction with ceftriaxone. Time-kill kinetics was performed to determine if the compounds were either bactericidal or bacteriostatic. The Pathogen Box compounds: MMV676501, MMV002817, MMV688327, MMV688508, MMV024937, MMV687798 (levofloxacin), MMV021013, and MMV688978 (auranofin) showed potent activity against resistant strains of
N. gonorrhoeae
at an MIC and MBC of ≤10 µM. Besides the eight compounds, MMV676388 and MMV272144 were active against susceptible
N. gonorrhoeae
strains, also at MIC and MBC of ≤10 µM. All the compounds were bactericidal and were either synergistic or additive with fractional inhibitory concentration index ranging between 0.40 and 1.8. The study identified novel Pathogen Box compounds with potent activity against
N. gonorrhoeae
strains and has the potential to be further investigated as primary or adjunctive therapy to treat gonococcal infections.
Drug distribution and efficacy of the DprE1 inhibitor BTZ-043 in the C3HeB/FeJ mouse tuberculosis model
Authors: Ramey Michelle E. , Kaya Firat , Bauman Allison A. , Massoudi Lisa M. , Sarathy Jansy P. , Zimmerman Matthew D. , Scott Dashick W. L. , Job Alyx M. , Miller-Dawson Jake A. , Podell Brendan K. , Lyons Michael A. , Dartois Véronique , Lenaerts Anne J. , Robertson Gregory T.
Published: October 2023

BTZ-043, a suicide inhibitor of the
Mycobacterium tuberculosis
cell wall synthesis decaprenylphosphoryl-beta-
D
-ribose 2′ epimerase, is under clinical development as a potential new anti-tuberculosis agent. BTZ-043 is potent and bactericidal
in vitro
but has limited activity against non-growing bacilli in rabbit caseum. To better understand its behavior
in vivo
, BTZ-043 was evaluated for efficacy and spatial drug distribution as a single agent in the C3HeB/FeJ mouse model presenting with caseous necrotic pulmonary lesions upon
Mycobacterium tuberculosis
infection. BTZ-043 promoted significant reductions in lung and spleen bacterial burdens in the C3HeB/FeJ mouse model after 2 months of therapy. BTZ-043 penetrates cellular and necrotic lesions and was retained at levels above the serum-shifted minimal inhibitory concentration in caseum. The calculated rate of kill was found to be highest and dose-dependent during the second month of treatment. BTZ-043 treatment was associated with improved histology scores of pulmonary lesions, especially compared to control mice, which experienced advanced fulminant neutrophilic alveolitis in the absence of treatment. These positive treatment responses to BTZ-043 monotherapy in a mouse model of advanced pulmonary disease can be attributed to favorable distribution in tissues and lesions, retention in the caseum, and its high potency and bactericidal nature at drug concentrations achieved in necrotic lesions.
High temperatures augment inhibition of parasites by a honey bee gut symbiont
Authors: Palmer-Young Evan C. , Markowitz Lindsey M. , Huang Wei-Fone , Evans Jay D.
Published: October 2023

Temperature affects growth, metabolism, and interspecific interactions in microbial communities. Within animal hosts, gut bacterial symbionts can provide resistance to parasitic infections. Both infection and populations of symbionts can be shaped by the host body temperature. However, the effects of temperature on the antiparasitic activities of gut symbionts have seldom been explored. The
Lactobacillus
-rich gut microbiota of facultatively endothermic honey bees is subject to seasonal and ontogenetic changes in host temperature that could alter the effects of symbionts against parasites. We used cell cultures of a
Lactobacillus
symbiont and an important trypanosomatid gut parasite of honey bees to test the potential for temperature to shape parasite-symbiont interactions. We found that symbionts showed greater heat tolerance than parasites and chemically inhibited parasite growth via production of acids. Acceleration of symbiont growth and acid production at high temperatures resulted in progressively stronger antiparasitic effects across a temperature range typical of bee colonies. Consequently, the presence of symbionts reduced both the peak growth rate and heat tolerance of parasites. Substantial changes in parasite-symbiont interactions were evident over a temperature breadth that parallels changes in diverse animals exhibiting infection-related fevers and the amplitude of circadian temperature variation typical of endothermic birds and mammals, implying the frequent potential for temperature to alter symbiont-mediated resistance to parasites in endo- and ectothermic hosts. Results suggest that the endothermic behavior of honey bees could enhance the impacts of gut symbionts on parasites, implicating thermoregulation as a reinforcer of core symbioses and possibly microbiome-mediated antiparasitic defense.

IMPORTANCE

Two factors that shape the resistance of animals to infection are body temperature and gut microbiota. However, temperature can also alter interactions among microbes, raising the question of whether and how temperature changes the antiparasitic effects of gut microbiota. Honey bees are agriculturally important hosts of diverse parasites and infection-mitigating gut microbes. They can also socially regulate their body temperatures to an extent unusual for an insect. We show that high temperatures found in honey bee colonies augment the ability of a gut bacterial symbiont to inhibit the growth of a common bee parasite, reducing the parasite’s ability to grow at high temperatures. This suggests that fluctuations in colony and body temperatures across life stages and seasons could alter the protective value of bees’ gut microbiota against parasites, and that temperature-driven changes in gut microbiota could be an underappreciated mechanism by which temperature—including endothermy and fever—alters animal infection.
Ectopic expression of murine CD163 enables cell-culture isolation of lactate dehydrogenase-elevating virus 63 years after its discovery
Authors: Shaw Teressa M. , Maloney Sara M. , Nennig Kylie , Ramuta Mitchell D. , Norton Andrew , Ibarra Rodrigo , Kuehnert Paul , Brinton Margo , Faaberg Kay , Kuhn Jens H. , O'Connor David H. , Warren Cody J. , Bailey Adam L.
Published: October 2023

Arteriviruses are RNA viruses related to coronaviruses but have not yet been associated with human infection. A murine arterivirus, lactate dehydrogenase-elevating virus (LDV), was first described in 1960 and quickly became a promising model for understanding immune failure due to its unique ability to persist in immunocompetent adult mice. However, the inability to culture LDV
in vitro
ultimately limited this system. Here, we demonstrate that the macrophage marker CD163 is essential for LDV infection. Expression of the murine homolog (mCD163) in otherwise mCD163-negative cell lines from mice and nonhuman primates enables productive LDV infection, creating the first immortalized cell-culture system. We also show that mCD163-knockout mice are completely resistant to LDV infection. These findings advance LDV as a model of arterivirus infection and viral persistence while adding to a growing body of literature suggesting that CD163 utilization is a broad feature of arteriviruses.

IMPORTANCE

Mouse models of viral infection play an especially large role in virology. In 1960, a mouse virus, lactate dehydrogenase-elevating virus (LDV), was discovered and found to have the peculiar ability to evade clearance by the immune system, enabling it to persistently infect an individual mouse for its entire lifespan without causing overt disease. However, researchers were unable to grow LDV in culture, ultimately resulting in the demise of this system as a model of failed immunity. We solve this problem by identifying the cell-surface molecule CD163 as the critical missing component in cell-culture systems, enabling the growth of LDV in immortalized cell lines for the first time. This advance creates abundant opportunities for further characterizing LDV in order to study both failed immunity and the family of viruses to which LDV belongs,
Arteriviridae
(aka, arteriviruses).
Palmitoylation of the hemagglutinin of influenza B virus by ER-localized DHHC enzymes 1, 2, 4, and 6 is required for efficient virus replication
Authors: Meng Xiaorong , Veit Michael
Published: October 2023

Covalent attachment of the fatty acid palmitate or stearate to the cytoplasmic domain of viral glycoproteins is often crucial for viral replication. This has previously been studied for the hemagglutinin (HA) of influenza A virus and the responsible enzymes have been identified, but similar studies have not been performed with HA of influenza B virus, which contains palmitate linked to two cysteines. We show here that the modification is required for efficient virus replication since exchange of both cysteines or the cysteine located at the end of the cytoplasmic tail prevented the generation of viable viruses. Viruses with an exchange of the membrane-proximal cysteine rapidly reverted back to wild-type virus. Blocking exit of proteins from the endoplasmic reticulum (ER) revealed that palmitoylation of HA of influenza B virus occurs in the ER, whereas acylation of HA of influenza A virus occurs in the Golgi. Infecting cells deficient in Asp-His-His-Cys (DHHC) palmitoyltransferases revealed that HA of influenza B virus is acylated by the ER-localized DHHCs 1, 2, 4, and 6, which are thus different from the enzymes previously identified for acylation of HA of influenza A virus. A comparison of predicted and experimentally determined protein structures suggests that the exclusive acylation of the HA of influenza B virus with palmitate is not a function of the responsible DHHCs and that the transmembrane region may be critical for the acylation of HA of influenza A and B viruses by different DHHCs.

IMPORTANCE

Influenza viruses are a public health concern since they cause seasonal outbreaks and occasionally pandemics. Our study investigates the importance of a protein modification called “palmitoylation” in the replication of influenza B virus. Palmitoylation involves attaching fatty acids to the viral protein hemagglutinin and has previously been studied for influenza A virus. We found that this modification is important for the influenza B virus to replicate, as mutating the sites where palmitate is attached prevented the virus from generating viable particles. Our experiments also showed that this modification occurs in the endoplasmic reticulum. We identified the specific enzymes responsible for this modification, which are different from those involved in palmitoylation of HA of influenza A virus. Overall, our research illuminates the similarities and differences in fatty acid attachment to HA of influenza A and B viruses and identifies the responsible enzymes, which might be promising targets for anti-viral therapy.
Phosphorylation of CFP10 modulates
Mycobacterium tuberculosis
virulence
Authors: Malakar Basanti , Chauhan Komal , Sanyal Priyadarshini , Naz Saba , Kalam Haroon , Vivek-Ananth R. P. , Singh Lakshya Veer , Samal Areejit , Kumar Dhiraj , Nandicoori Vinay Kumar
Published: October 2023

Virulence effectors secreted by
Mycobacterium tuberculosis
(
Mtb
) help subvert host immune mechanisms and, therefore, are critical for establishing infection and pathogenesis. However, knowledge in terms of signaling mechanisms that modulate the secretion of virulence factors is sparse. We performed high-throughput secretome, phosphoproteome, and phospho-secretome analysis of
Mtb
. We combined the analysis with empirical validations to show regulation of mycobacterial secretion through protein phosphorylation. System level protein-protein interaction network analysis superimposed with the secretome, phosphoproteome, and phospho-secretome profile revealed an intricate relationship between phosphorylation and secretion. At the core of the network was a key virulence factor CFP10. We identified PknA to be the kinase responsible for phosphorylating CFP10. Using genetic tools, we show that phosphomimetic mutation of CFP10 negatively regulates the secretion of virulence mediator ESAT6. Significantly, the dynamics of CFP10 phosphorylation strongly influenced bacterial virulence and survival within macrophages and mice. Together, the results show that the dynamic phosphorylation status of the secretory protein CFP10 regulates the secretion of virulence factors and impacts virulence.

IMPORTANCE

Secreted virulence factors play a critical role in bacterial pathogenesis. Virulence effectors not only help bacteria to overcome the host immune system but also aid in establishing infection.
Mtb
, which causes tuberculosis in humans, encodes various virulence effectors. Triggers that modulate the secretion of virulence effectors in
Mtb
are yet to be fully understood. To gain mechanistic insight into the secretion of virulence effectors, we performed high-throughput proteomic studies. With the help of system-level protein-protein interaction network analysis and empirical validations, we unravelled a link between phosphorylation and secretion. Taking the example of the well-known virulence factor of CFP10, we show that the dynamics of CFP10 phosphorylation strongly influenced bacterial virulence and survival
ex vivo
and
in vivo
. This study presents the role of phosphorylation in modulating the secretion of virulence factors.
A novel, highly sensitive, one-tube nested quantitative real-time PCR for
Brucella
in human blood samples
Authors: Liu Li , Li Mengyao , Liu Gaowen , He Jian , Liu Yang , Chen Xuesong , Tu Yungui , Lin Jie , Feng Yue , Xia Xueshan
Published: October 2023

Brucellosis is a zoonotic disease caused by
Brucella
spp. and is a major threat to human and livestock health. The accurate and rapid detection of
Brucella
DNA is essential for the diagnosis and treatment of this disease. However, traditional diagnostic methods, such as culture and serological tests, have limitations in terms of sensitivity, specificity, and time consumption. To address these challenges, we developed a highly sensitive one-tube nested quantitative real-time PCR (qPCR) method to detect
Brucella
DNA using a closed-tube approach with two primers and two probes that sequentially react with encoding a
Brucella
outer membrane protein. The analytical sensitivity of this one-tube nested qPCR approach was 100 fg/μL, which is 100-fold higher than that of a conventional qPCR. Intra-batch and inter-batch replicates showed low coefficients of variation, both less than 5%. The study included 250 clinical samples, showing that this one-tube nested qPCR method has a specificity of 100% and a sensitivity of 98.6%, exceeding the sensitivity of conventional qPCR (84.1%) at a cycle threshold (CT) cutoff of 38. More importantly, the one-tube nested qPCR reduced the CT values by an average of 6.4 compared to conventional qPCR, significantly improving the detection rate of low-load samples (CT > 35). In conclusion, the
bcsp31
one-tube nested qPCR method is a promising tool for the detection of brucellosis, owing to its high sensitivity and operational simplicity. This study highlights the potential of qPCR-based methods to improve the accuracy and speed of brucellosis diagnoses.

IMPORTANCE

This study developed a highly sensitive and efficient method for the detection of brucellosis by introducing a one-tube nested quantitative real-time PCR (qPCR) approach, representing a remarkable advance in the field. The method demonstrated an impressive analytical sensitivity of 100 fg/μL, surpassing conventional qPCR and enabling the detection of even low levels of
Brucella
DNA. In addition, the study’s comprehensive evaluation of 250 clinical samples revealed a specificity of 100% and a sensitivity of 98.6%, underscoring its reliability and accuracy. Most importantly, the new method significantly improved the detection rate of low-burden samples, reducing cycle threshold values by an average of 6.4. These results underscore the immense potential of this approach to facilitate rapid and accurate brucellosis diagnosis, which is critical for effective disease management and control.
Anomalous thermal structures of subduction zones revealed by thermal properties of clinochlore at high temperature and pressure
Authors: Zhang Ruixin , Wang Duojun , Tan Huiwen , Lu Hongbin , Miao Sheqiang , Gao Xiang , Han Kenan , Chen Peng , Liu Chuanjiang , Cai Nao
Published: October 2023

Clinochlore is a major hydrous mineral in subduction zones, and its thermophysical properties at high temperature and pressure are critical to the thermal structures of subduction zones. Here, we used the pulse heating method to measure thermal diffusivity and thermal conductivity of clinochlore at 0.5−4.0 GPa and 298−1373 K. Our results indicate that upon heating, thermal diffusivity and thermal conductivity decrease from ∼9.6 × 10−7 m2 s−1 to 4.3 × 10−7 m2 s−1 and from ∼3.5 W m−1 K−1 to 1.9 W m−1 K−1, respectively, before dehydration, but this trend is reversed after dehydration. In general, the pressure derivatives for the thermal transport properties also decrease with temperature before dehydration. Lattice heat transfer is the dominant mechanism before dehydration, but fluid is involved after dehydration. Using our experimental data, we simulated the temperature distribution of subducting slabs containing clinochlore at volume fractions of 0%, 10%, 20%, 50%, and 100%. Our simulations showed that the heat insulation effect caused by the presence of clinochlore could result in an increase in temperature by 30−60 K for the upper part of the subducting slab.
Identifying plutons associated with long-lived volcanism by thermal modeling of contact metamorphic aureoles
Authors: Yamaoka Ken , Wallis Simon R. , Miyake Akira , Annen Catherine
Published: October 2023

A compilation of the thicknesses of contact metamorphic aureoles (CMAs) developed around intermediate to felsic plutons shows many CMAs are far broader than expected by commonly used thermal models for pluton emplacement. Shortfalls in the amount of heat potentially provided based on pluton size, compared to that needed to form the observed CMA, can be accounted for if some hot magma has been lost by volcanic eruption after passing through the pluton domain and replaced by new hot magma. A high ambient temperature may also contribute to broad CMA formation. However, the presence of coeval pairs of both narrow and broad CMAs in the same area requires contrasting types of pluton growth history. Our thermal modeling, constrained by the peak metamorphic temperature, shows the broad CMA of a well-developed pair of CMAs in the Hongusan area of Japan is due to a magmatic history, including magma tapping and replenishment. A global compilation of CMAs suggests more than 30% of plutons are associated with broad CMAs and fed contemporaneous volcanic eruption.
Augmentation of triceps tendon repair with a bio-inductive collagen scaffold
Authors: Welborn Benjamin , White Charles Cody , Bruce Jeremy R
Published: October 2023

Two active, adult male patients, one with prior triceps rupture and direct repair, presented with traumatic rupture of the distal triceps tendon. MRI confirmed not only complete rupture with retraction in both, but also signal changes within the tendon, raising concern for healing potential and re-rupture. Surgical repair was performed using heavy, non-absorbable suture and suture anchors in the standard fashion, followed by augmentation with a bovine, bio-inductive collagen scaffold in order to increase tendon thickness and aid with healing capability. This technique is well described for rotator cuff repair augmentation but is a novel technique to the literature in the setting of triceps tendons repair. Both patients returned to full, preinjury activity without complication with sustained results at 3 and 3.5 years postoperatively.
What should all health professionals know about movement behaviour change? An international Delphi-based consensus statement
Authors: Alsop Tahlia , Lehman Emily , Brauer Sandra , Forbes Roma , Hanson Coral L , Healy Genevieve , Milton Karen , Reid Hamish , Rosbergen Ingrid , Gomersall Sjaan
Published: October 2023

The WHO has called for action to integrate physical activity promotion into healthcare settings, yet there is a lack of consensus on the competencies required by health professionals to deliver effective movement behaviour change support. The objective of this study was to establish key competencies relevant for all health professionals to support individuals to change their movement behaviours. Consensus was obtained using a three-phase Delphi process. Participants with expertise in physical activity and sedentary behaviour were asked to report what knowledge, skills and attributes they believed health professionals should possess in relation to movement behaviour change. Proposed competencies were developed and rated for importance. Participants were asked to indicate agreement for inclusion, with consensus defined as group level agreement of at least 80%. Participants from 11 countries, working in academic (55%), clinical (30%) or combined academic/clinical (13%) roles reached consensus on 11 competencies across 3 rounds (n=40, n=36 and n=34, respectively). Some competencies considered specific to certain disciplines did not qualify for inclusion. Participants agreed that health professionals should recognise, take ownership of, and practise interprofessional collaboration in supporting movement behaviour change; support positive culture around these behaviours; communicate using person-centred approaches that consider determinants, barriers and facilitators of movement behaviours; explain the health impacts of these behaviours; and recognise how their own behaviour influences movement behaviour change support. This consensus defines 11 competencies for health professionals, which may serve as a catalyst for building a culture of advocacy for movement behaviour change across health disciplines.
Evaluation of effectiveness and safety of the CorPath GRX robotic system in endovascular embolization procedures of cerebral aneurysms
Authors: Mendes Pereira Vitor , Rice Hal , De Villiers Laetitia , Sourour Nader , Clarencon Frédéric , Spears Julian , Tomasello Alejandro , Hernandez David , Cancelliere Nicole M , Liu Xiao Yu Eileen , Nicholson Patrick , Costalat Vincent , Gascou Gregory , Mordasini Pasquale , Gralla Jan , Martínez-Galdámez Mario , Galvan Fernandez Jorge , Killer-Oberpfalzer Monika , Liebeskind David S , Turner Raymond D , Blanc Raphael , Piotin Michel
Published: October 2023

Background

Robotic-assisted neurointervention was recently introduced, with implications that it could be used to treat neurovascular diseases.

Objective

To evaluate the effectiveness and safety of the robotic-assisted platform CorPath GRX for treating cerebral aneurysms.

Methods

This prospective, international, multicenter study enrolled patients with brain aneurysms that required endovascular coiling and/or stent-assisted coiling. The primary effectiveness endpoint was defined as successful completion of the robotic-assisted endovascular procedure without any unplanned conversion to manual treatment with guidewire or microcatheter navigation, embolization coil(s) or intracranial stent(s) deployment, or an inability to navigate vessel anatomy. The primary safety endpoint included intraprocedural and periprocedural events.

Results

The study enrolled 117 patients (74.4% female) with mean age of 56.6 years from 10 international sites,. Headache was the most common presenting symptom in 40/117 (34.2%) subjects. Internal carotid artery was the most common location (34/122, 27.9%), and the mean aneurysm height and neck width were 5.7±2.6 mm and 3.5±1.4 mm, respectively. The overall procedure time was 117.3±47.3 min with 59.4±32.6 min robotic procedure time. Primary effectiveness was achieved in 110/117 (94%) subjects with seven subjects requiring conversion to manual for procedure completion. Only four primary safety events were recorded with two intraprocedural aneurysm ruptures and two strokes. A Raymond-Roy Classification Scale score of 1 was achieved in 71/110 (64.5%) subjects, and all subjects were discharged with a modified Rankin Scale score of ≤2.

Conclusions

This first-of-its-kind robotic-assisted neurovascular trial demonstrates the effectiveness and safety of the CorPath GRX System for endovascular embolization of cerebral aneurysm procedures.

Trial registration number

NCT04236856
Joint analysis of macroscopic response and microfabric evolution of coral sand during earthquake-induced liquefaction
Authors: Wu Qi , Ding Xuanming , Zhang Yanling
Published: October 2023

This study addresses the microfabric evolution of coral sand during earthquake-induced liquefaction using the joint tests of macroscopic shaking table and microscopic X-ray computed tomography. Based on the non-destructive scanning and image reconstruction in three-dimensional, the change in the grain–pore structure of sands under earthquakes is discussed. Furthermore, the special microstructural evolution of coral sand is studied by the contrast tests with Fujian sand. The results show that the coordination number of coral sand is larger than that of Fujian sand after liquefaction, which is consistent with that the reduction in acceleration of coral sand is smaller than that of the Fujian sand, and the coral sand foundation still has a larger shear strength due to the smaller excess pore pressure accumulation. Moreover, the contact index of Fujian sand and Reigate sand fluctuates in a similar range with the change of void ratio and coordination number compared with coral sand. This is due to the fact that the Fujian sand and Reigate sand are both general terrigenous sands (quartz sand), while coral sand has irregular particle shapes and larger surface friction caused by marine biogenesis. The test results deepen the understanding of the liquefaction mechanism of coral sand.
Hierarchical model to predict common carp and bigmouth buffalo abundance from electrofishing data
Authors: Simonson Martin A. , Weber Michael J. , McCombs Audrey L. , Annear Andrew R.
Published: October 2023

Catch per unit effort (CPUE) is used as an index of fish abundance under the premise that changes in CPUE result from changes in true density. However, catchability may also vary based on environmental conditions that affect observed CPUE. We developed a hierarchical model for estimating common carp ( Cyprinus carpio) and bigmouth buffalo ( Ictiobus cyprinellus) relative abundance with electrofishing survey data from six shallow lakes in northwest Iowa, USA, between 2018 and 2020. Common carp catchability was negatively associated with lake perimeter but unrelated to lake surface area, water depth, Secchi depth, temperature, and month of sampling. Bigmouth buffalo catchability was negatively associated with Secchi depth and water temperature and unrelated to other environmental variables. Hierarchical model posterior distributions of bigmouth buffalo density were less precise than Schnabel estimates, whereas common carp posterior distribution abundance estimates were more precise than Schnabel estimates. Our results indicate that hierarchical models can be a viable substitute for labor-intensive capture–mark–recapture methods to estimate unknown latent variables like relative abundance, and could be applied to other species, sampling gears, and management frameworks.
Assessing small pelagic fish trends in space and time using piscivore stomach contents
Authors: Gaichas Sarah K. , Gartland James , Smith Brian E. , Wood Anthony D. , Ng Elizabeth L. , Celestino Michael , Drew Katie , Tyrell Abigail S. , Thorson James T.
Published: October 2023

Changing distribution and abundance of small pelagic fishes may drive changes in predator distributions, affecting predator availability to fisheries and surveys. However, small pelagics are difficult to survey directly, so we developed a novel method of assessing the aggregate abundance of 21 small pelagic forage taxa via predator stomach contents. We used stomach contents collected from 22 piscivore species captured by multiple bottom trawl surveys within a vector autoregressive spatio-temporal model to assess trends of small pelagics on the Northeast US shelf. The goal was to develop a spatial “forage index” to inform survey and (or) fishery availability in the western North Atlantic bluefish ( Pomatomus saltatrix) stock assessment. This spatially resolved index compared favorably with more traditional design-based survey biomass indices for forage species well sampled by surveys. However, our stomach content-based index better represented smaller unmanaged forage species that surveys are not designed to capture. The stomach-based forage index helped explain bluefish availability to the recreational fishery for stock assessment and provided insight into pelagic forage trends throughout the regional ecosystem.