bluuebunny/crossref_metadata_2025_split huggingface dataset:
The resuscitation-promoting factor (Rpf) from Micrococcus luteus and its putative reaction product 1,6-anhydro-MurNAc increase culturability of environmental bacteria
Authors: Guzman Juan , Raval Dipansi , Hauck Dirk , Titz Alexander , Poehlein Anja , Degenkolb Thomas , Daniel Rolf , Vilcinskas Andreas 
Published: September 2023

Bacterial dormant cells do not divide and are not immediately culturable, but they persist in a state of low metabolic activity, a physiological state having clinical relevance, for instance in latent tuberculosis. Resuscitation promoting factors (Rpf) are proteins that act as signaling molecules mediating growth and replication. In this study we aimed to test the effect of Rpf from Micrococcus luteus on the number and diversity of cultured bacteria using insect and soil samples, and to examine if the increase in culturability could be reproduced with the putative reaction product of Rpf, 1,6-anhydro-MurNAc. The rpf gene from M. luteus was amplified and cloned into a pET21b expression vector and the protein was expressed in E. coli BL21(DE3) cells and purified by affinity chromatography using a hexa-histidine tag. 1,6-anhydro-N-acetylmuramic acid (1,6-anhydro-MurNAc) was prepared using reported chemical synthesis methods. Recombinant Rpf protein or 1,6-anhydro-MurNAc were added to R2A cultivation media, and their effect examined on the culturability of bacteria from eight environmental samples including four cockroach guts and four soils. Colony forming units, 16S rRNA gene copies and Illumina amplicon sequencing of the 16S rRNA gene were measured for all eight samples subjected to three different treatments: Rpf, 1,6-anhydro-MurNAc or blank control. Both Rpf and 1,6-anhydro-MurNAc increased the number of colony forming units, and 16S rRNA gene copies across the samples although the protein was more effective. The Rpf and 1,6-anhydro-MurNAc promoted the cultivation of a diverse set of bacteria and specially certain clades of the phyla Actinomycetota and Bacillota. This study opens the path for improved cultivation strategies aiming to isolate and study yet undescribed living bacterial organisms.
Efficacy of Shock Team Implementation for Cardiogenic Shock: A Systematic Review
Authors: Abdelnabi Mohamed , Elsaeidy Ahmed Saad , Aboutaleb Aya Moustafa , Johanis Amit , Ghanem Ahmed K. , Abdelazeem Basel 
Published: September 2023

AbstractIntroductionCardiogenic shock (CS) is a critical cardiac condition characterized by low cardiac output leading to end-organ hypoperfusion and associated with high in-hospital mortality rates. It can manifest following acute myocardial infarction or acute exacerbation of chronic heart failure. Despite advancements, mortality rates remain elevated, prompting interest in multidisciplinary approaches to improve outcomes. This manuscript presents a review focused on the concept of a CS team and its potential impact on patient management and outcomes.MethodsA comprehensive search was performed on March 19th, 2023, covering PubMed, Web of Science, Scopus, Embase, and Cochrane Library. We included primary studies (prospective and retrospective) only and evaluated their quality using the Newcastle-Ottawa Quality Scale. This review was registered in PROSPERO (CRD42023440354).ResultsSix relevant studies with 2066 CS patients were included, of which 1071 were managed by shock teams and 995 received standard care. Findings from the reviewed studies indicated the favorable outcomes associated with implementing CS teams. Patients managed by these teams exhibited higher 30-day and in-hospital survival rates compared to those without team intervention. The implementation of CS teams was linked to reduced in-hospital and ICU mortality rates. Additionally, shock team involvement was associated with shorter door-to-balloon times.ConclusionThis review highlighted the positive influence of CS teams on patient care, enabling early detection, timely interventions, and shorter ICU stays. Despite implementation challenges, CS teams hold promise for improving management outcomes, necessitating increased attention and ongoing research in multidisciplinary strategies to advance CS care.
Predictors for the Recurrence and Prognosis of Stroke patients within a Multi-Ethnic Asian Population
Authors: Lee Keng Siang , Siow Isabel , Riandini Tessa , Narasimhalu Kaavya , Tan Kelvin Bryan , De Silva Deidre Anne 
Published: September 2023

AbstractObjectiveThere is a paucity of studies investigating the risk profile, and outcomes amongst young versus old stroke patients in Asian populations. Singapore is uniquely placed to contribute to the understanding of these risk factors, given our multi-ethnic population. Therefore, the aim of this study was to identify predictors of recurrence and outcome in stroke, comparing the young and the older stroke patients in Singapore.MethodsThis cohort study adhered to STROBE guidelines. Data were obtained from the Singapore Stroke Registry (SSR) from 2005 to 2016, to compare outcomes after first stroke among young (18-49 years) and among old stroke (≥50 years) patients. Outcome measures included recurrent stroke, acute myocardial infarction (AMI) and death from the above. Cox proportional hazards models were performed to determine risk factors for time to each outcome after first stroke, which included demographic and comorbidity variables.ResultsA total of 64,915 patients (6,705 young, and 58,210 old) were included in our analysis. After adjusting for gender, ethnicity, and comorbidities, old stroke patients have a greater hazard for recurrent stroke (HR = 1.20, 95%CI: 1.11-1.29), AMI (HR = 1.72, 95%CI: 1.52-1.94), and for recurrent stroke/AMI (HR = 1.36, 95%CI: 1.27-1.45). The old stroke patients were also more likely to die than younger stroke patients (HR = 2.62, 95%CI: 2.48-2.78). Amongst young stroke patients, males were at greater hazards for recurrent stroke (HR = 1.18, 95%CI: 1.00-1.38), AMI (HR = 1.40, 95%CI: 1.07-1.82), recurrent stroke/AMI (HR = 1.17, 95%CI: 1.02-1.36). However, males were at reduced hazards for death (HR = 0.87, 95%CI: 0.77-0.98). When analysing specifically young stroke patients, compared with the Chinese ethnicity, the Malay ethnicity was predisposed to recurrent stroke (HR = 1.36, 95%CI: 1.14-1.64). Compared with the Chinese ethnicity, both the Malay and Indian ethnicities were predisposed to AMI. The Malay ethnicity was at greater hazards for death (HR = 1.45, 95%CI: 1.27-1.66).ConclusionsNon-Chinese ethnicities, especially Malay and Indian ethnicities experience poorer outcomes after first stroke. Further optimisation of risk factors targeting these high-priority populations are needed to achieve high quality care.
Efficient ultrasound-mediated drug delivery to orthotopic liver tumors – Direct comparison of doxorubicin-loaded nanobubbles and microbubbles
Authors: Nittayacharn Pinunta , Abenojar Eric , Cooley Michaela , Berg Felipe , Counil Claire , Sojahrood Amin Jafari , Khan Muhammad Saad , Yang Celina , Berndl Elizabeth , Golczak Marcin , Kolios Michael C. , Exner Agata A. 
Published: September 2023

AbstractLiver metastasis is a major obstacle in treating aggressive cancers, and current therapeutic options often prove insufficient. To overcome these challenges, there has been growing interest in ultrasound-mediated drug delivery using lipid-shelled microbubbles (MBs) and nanobubbles (NBs) as promising strategies for enhancing drug delivery to tumors. Our previous work demonstrated the potential of Doxorubicin-loaded C3F8NBs (hDox-NB, 280 ± 123 nm) in improving cancer treatment in vitro using low-frequency ultrasound. In this study, we investigated the pharmacokinetics and biodistribution of sonicated hDox-NBs in orthotopic rat liver tumors. We compared their delivery and therapeutic efficiency with size-isolated MBs (hDox-MB, 1104 ± 373 nm). Results showed a similar accumulation of hDox in tumors treated with hDox-MBs and unfocused therapeutic ultrasound (hDox-MB+TUS) and hDox-NB+TUS. However, significantly increased apoptotic cell death in the tumor and fewer off-target apoptotic cells in the normal liver were found upon the treatment with hDox-NB+TUS. The tumor-to-liver apoptotic ratio was elevated 9.4-fold following treatment with hDox-NB+TUS compared to hDox-MB+TUS, suggesting that the therapeutic efficacy and specificity are significantly increased when using hDox-NB+TUS. These findings highlight the potential of this approach as a viable treatment modality for liver tumors. By elucidating the behavior of drug-loaded bubblesin vivo, we aim to contribute to developing more effective liver cancer treatments that could ultimately improve patient outcomes and decrease off-target side effects.
Localization of four class I glutaredoxins in the cytosol and the secretory pathway and characterization of their biochemical diversification
Authors: Schlößer Michelle , Moseler Anna , Bodnar Yana , Homagk Maria , Wagner Stephan , Pedroletti Luca , Gellert Manuela , Ugalde José M. , Lillig Christopher H. , Meyer Andreas J. 
Published: September 2023

AbstractClass I glutaredoxins (GRXs) are catalytically active oxidoreductases and considered key proteins mediating reversible glutathionylation and deglutathionylation of protein thiols during development and stress responses. To narrow in on putative target proteins, it is mandatory to know the subcellular localization of the respective GRXs and to understand their catalytic activities and putative redundancy between isoforms in the same compartment. We show that GRXC1 and GRXC2 are cytosolic proteins with GRXC1 being attached to membranes through myristoylation. GRXC3 and GRXC4 are identified as type II membrane proteins along the early secretory pathway with their enzymatic function on the luminal side. Comparison of all four studied GRXs for their oxidoreductase function highlights biochemical diversification with GRXC1 and GRXC2 being better reductants than GRXC3 and GRXC4 with bis(2-hydroxyethyl) disulfide and oxidized roGFP2 as substrates.Vice versa, GRXC3 and GRXC4 are better oxidants of reduced roGFP2 in the reverse reaction. Analysis of electrostatic surface potentials mirrors the phylogenetic classification of class I GRXs but cannot fully account for the observed kinetic differences in their interaction with roGPF2. Despite localization of two class I GRXs each in the cytosol and the endomembrane system, the respective double null mutants are viable without obvious phenotypes.Summary statementWe identify Arabidopsis glutaredoxins GRXC3 and GRXC4 as type II membrane proteins in the secretory pathway and GRXC1 as attached to membranes through N-terminal myristoylation. Cytosolic GRXC1 and GRXC2 and luminal GRXC3 and GRXC4 display distinct biochemical properties in their redox activities.
Magnetoelectrics Enables Large Power Delivery to mm-Sized Wireless Bioelectronics
Authors: Kim Wonjune , Tuppen C. Anne , Alrashdan Fatima , Singer Amanda , Weirnick Rachel , Robinson Jacob T. 
Published: September 2023

AbstractTo maximize the capabilities of minimally invasive implantable bioelectronic devices, we must deliver large amounts of power to small implants; however, as devices are made smaller, it becomes more difficult to transfer large amounts of power without a wired connection. Indeed, recent work has explored creative wireless power transfer (WPT) approaches to maximize power density (the amount of power transferred divided by receiver footprint area (length × width)). Here, we analyzed a model for WPT using magnetoelectric (ME) materials that convert an alternating magnetic field into an alternating voltage. With this model, we identify the parameters that impact WPT efficiency and optimize the power density. We find that improvements in adhesion between the laminated ME layers, clamping, and selection of material thicknesses lead to a power density of 3.1 mW/mm2, which is over 4 times larger than previously reported for mm-sized wireless bioelectronic implants at a depth of 1 cm or more in tissue. This improved power density allows us to deliver 31 mW and 56 mW to 10-mm2and 27-mm2ME receivers, respectively. This total power delivery is over 5 times larger than similarly sized bioelectronic devices powered by radiofrequency electromagnetic waves, inductive coupling, ultrasound, light, capacitive coupling, or previously reported magnetoelectrics. This increased power density opens the door to more power-intensive bioelectronic applications that have previously been inaccessible using mm-sized battery-free devices.
Probing the stability and interdomain interactions in the ABC transporter OpuA, using single-molecule optical tweezers
Authors: van der Sleen Lyan , Stevens Jan , Marrink Siewert J. , Poolman Bert , Tych Kasia 
Published: September 2023

SummaryTransmembrane transporter proteins are essential for the maintenance of cellular homeostasis and, as such, are key drug targets. Many transmembrane transporter proteins are known to undergo large structural rearrangements during their functional cycles. Despite the large amount of detailed structural and functional data available for these systems, our understanding of their dynamics and therefore how they function is generally limited. We introduce an innovative approach which enables us to directly measure the dynamics and stabilities of inter-domain interactions of transmembrane proteins using optical tweezers. Focusing on the osmoregulatory ABC transporter OpuA fromLactococcus lactis, we examine the mechanical properties and potential interactions of its substrate-binding domains. Our measurements are performed in lipid nanodiscs, providing a native-mimicking environment for the transmembrane protein. The technique provides high spatial and temporal resolution and allows us to study the functionally-relevant motions and inter-domain interactions of individual transmembrane transporter proteins in real-time in a lipid bilayer.
A congestion downstream of PSI causes the over-reduction of the electron transport chain inpgr5independent of membrane energization
Authors: Kappel Sandrine , Thiele Wolfram , Gefen-Treves Shany , Henze Anita , Armbruster Ute , Schöttler Mark Aurel 
Published: September 2023

AbstractThe thylakoid protein Proton Gradient Regulation5 (PGR5) is thought to be a key component of cyclic electron flux around photosystem I. Thepgr5mutant is characterized by impaired proton motive force (pmf) formation across the thylakoid membrane, decreased photoprotective non-photochemical quenching (NPQ), and an over-reduction of the PSI acceptor side. This over-reduction has been attributed to impaired photosynthetic control, which down-regulates plastoquinol re-oxidation at the cytochrome b6f complex when the lumen is strongly acidified. Here, using thecgl160ATP synthase assembly mutant, we show that incgl160 pgr5double mutants, both the pmf across the thylakoid membrane and NPQ are fully restored to wild-type levels. However, the acceptor-side limitation of PSI in the double mutants stays comparable to the singlepgr5mutant. This demonstrates that impaired photosynthetic control is not causal for the over-reduction of the PSI acceptor side inpgr5. Instead, we show that both inpgr5and theclg160 pgr5mutants, the entire high-potential chain from cytochrome f to PSI remains strongly reduced in high light. This leads to insufficient oxidizing power for plastoquinol re-oxidation by the cytochrome b6f complex, thus impairing pmf formation. We conclude that PGR5 plays a critical role in electron partitioning downstream of PSI.
Historical causes for the greater proportion of polyploid plants in higher latitudes
Authors: Hagen Eric R. , Vasconcelos Thais , Boyko James D. , Beaulieu Jeremy M. 
Published: September 2023

AbstractPremise of the StudyThe proportion of polyploid plants in a community increases with latitude, and different hypotheses have been proposed about which factors drive this pattern. Here, we aim to understand the historical causes of the latitudinal polyploidy gradient using a combination of ancestral state reconstruction methods. Specifically, we assess whether (1) polyploidization enables movement to higher latitudes (i.e., polyploidization precedes occurrences in higher latitudes) or (2) higher latitudes facilitate polyploidization (i.e., occurrence in higher latitudes precedes polyploidization).MethodsWe reconstruct the ploidy states and ancestral niches of 1,032 angiosperm species at four paleoclimatic time slices ranging from 3.3 million years ago to the present, comprising taxa from four well-represented clades: Onagraceae, Primulaceae,Solanum(Solanaceae), and Pooideae (Poaceae). We use ancestral niche reconstruction models alongside a customized discrete character evolution model to allow reconstruction of states at specific time slices. Patterns of latitudinal movement are reconstructed and compared in relation to inferred ploidy shifts.Key ResultsWe find that no single hypothesis applies equally well across all analyzed clades. While significant differences in median latitudinal occurrence were detected in the largest clade, Pooideae, no significant differences were detected in latitudinal movement in any clade.ConclusionsOur preliminary study is the first to attempt to connect ploidy changes to continuous latitudinal movement, but we cannot favor one hypothesis over another. Given that patterns seem to be clade-specific, a larger number of clades must be analyzed in future studies for generalities to be drawn.
Focused ultrasound ablation of melanoma with boiling histotripsy yields abscopal tumor control and antigen-dependent dendritic cell activation
Authors: Thim Eric A. , Kitelinger Lydia E. , Rivera-Escalera Fátima , Mathew Alexander S. , Elliott Michael R. , Bullock Timothy N. J. , Price Richard J. 
Published: September 2023

AbstractBackgroundBoiling histotripsy (BH), a mechanical focused ultrasound ablation strategy, can elicit intriguing signatures of anti-tumor immunity. However, the influence of BH on dendritic cell function is unknown, compromising our ability to optimally combine BH with immunotherapies to control metastatic disease.MethodsBH was applied using a sparse scan (1 mm spacing between sonications) protocol to B16F10-ZsGreen melanoma in bilateral and unilateral settings. Ipsilateral and contralateral tumor growth was measured. Flow cytometry was used to track ZsGreen antigen and assess how BH drives dendritic cell behavior.ResultsBH monotherapy elicited ipsilateral and abscopal tumor control in this highly aggressive model. Tumor antigen presence in immune cells in the tumor-draining lymph nodes (TDLNs) was ∼3-fold greater at 24h after BH, but this abated by 96h. B cells, macrophages, monocytes, granulocytes, and both conventional dendritic cell subsets (i.e. cDC1s and cDC2s) acquired markedly more antigen with BH. BH drove activation of both cDC subsets, with activation being dependent upon tumor antigen acquisition. Our data also suggest that BH-liberated tumor antigen is complexed with damage-associated molecular patterns (DAMPs) and that cDCs do not traffic to the TDLN with antigen. Rather, they acquire antigen as it flows through afferent lymph vessels into the TDLN.ConclusionWhen applied with a sparse scan protocol, BH monotherapy elicits abscopal melanoma control and shapes dendritic cell function through several previously unappreciated mechanisms. These results offer new insight into how to best combine BH with immunotherapies for the treatment of metastatic melanoma.Graphical Abstract
Ecological feedback limits the spread of an adaptive β-lactamase mutant
Authors: Ruelens Philip , de Ridder Eline , de Visser J. Arjan G.M. , Wortel Meike 
Published: September 2023

Abstractβ-lactamases play an important role in global health problems due to antibiotic resistant bacterial infections. Understanding the spread of these enzymes may inform the development of better drug therapies. However, this is challenging, as β-lactamases affect their own selective advantage through antibiotic degradation, creating complex eco-evolutionary feedback. We investigated the effect of such feedback on the spread of bacterial strains expressing different β-lactamase enzymes conferring varying levels of resistance to the cephalosporin cefotaxime. Specifically, we conducted head-to-head competitions between two related clinically observed β-lactamase mutants, TEM-19 and TEM-52, and varied cefotaxime concentration and cell density to explore the impact of these factors on competitive fitness and coexistence. The results revealed that cell density, which modulates feedback strength, determined whether resistance alleles could replace susceptible alleles or coexist with them. Using a population dynamic model based only on measured parameters, we investigated the underlying mechanisms of these dynamics. By validating our model with experimental data, we show that it can to a large extend predict the equilibrium frequencies based on dose-dependent growth rates and antibiotic degradation activities of the individual strains. Our study emphasizes the importance of considering ecological feedback in the evolution of antibiotic resistance and the potential for predictive modelling, which could be applied in clinical contexts.
Propofol-mediated loss of consciousness disrupts predictive routing and local field phase modulation of neural activity
Authors: Xiong Yihan (Sophy) , Donoghue Jacob A. , Lundqvist Mikael , Mahnke Meredith , Major Alex James , Brown Emery N. , Miller Earl K. , Bastos André M. 
Published: September 2023

AbstractPredictive coding is a fundamental function of the cortex. The predictive routing model proposes a neurophysiological implementation for predictive coding. Predictions are fed back from deep-layer cortex via alpha/beta (8-30Hz) oscillations. They inhibit the gamma (40-100Hz) and spiking that feed sensory inputs forward. Unpredicted inputs arrive in circuits unprepared by alpha/beta, resulting in enhanced gamma and spiking. To test the predictive routing model and its role in consciousness, we collected data from intracranial recordings of macaque monkeys during passive presentation of auditory oddballs (e.g., AAAAB) before and after propofol-mediated loss of consciousness (LOC). In line with the predictive routing model, alpha/beta oscillations in the awake state served to inhibit the processing of predictable stimuli. Propofol-mediated LOC eliminated alpha/beta modulation by a predictable stimulus in sensory cortex and alpha/beta coherence between sensory and frontal areas. As a result, oddball stimuli evoked enhanced gamma power, late (> 200 ms from stimulus onset) period spiking, and superficial layer sinks in sensory cortex. Therefore, auditory cortex was in a disinhibited state during propofol-mediated LOC. However, despite these enhanced feedforward responses in auditory cortex, there was a loss of differential spiking to oddballs in higher order cortex. This may be a consequence of a loss of within-area and inter-area spike-field coupling in the alpha/beta and gamma frequency bands. These results provide strong constraints for current theories of consciousness.Significance statementNeurophysiology studies have found alpha/beta oscillations (8-30Hz), gamma oscillations (40-100Hz), and spiking activity during cognition. Alpha/beta power has an inverse relationship with gamma power/spiking. This inverse relationship suggests that gamma/spiking are under the inhibitory control of alpha/beta. The predictive routing model hypothesizes that alpha/beta oscillations selectively inhibit (and thereby control) cortical activity that is predictable. We tested whether this inhibitory control is a signature of consciousness. We used multi-area neurophysiology recordings in monkeys presented with tone sequences that varied in predictability. We recorded brain activity as the anesthetic propofol was administered to manipulate consciousness. Compared to conscious processing, propofol-mediated unconsciousness disrupted alpha/beta inhibitory control during predictive processing. This led to a disinhibition of gamma/spiking, consistent with the predictive routing model.