bluuebunny/crossref_metadata_2025_split huggingface dataset:
Micrometer-thick, porous, nanocomposite coating for electrochemical sensors with exceptional antifouling and electroconducting properties
Authors: Lee Jeong-Chan , Kim Su Yeong , Song Jayeon , Jang Hyowon , Kim Hanul , Choi Siyoung Q. , Kim Sunjoo , Jolly Pawan , Kang Taejoon , Park Steve , Ingber Donald E. 
Published: September 2023

ABSTRACTDevelopment of coating technologies for electrochemical sensors that consistently exhibit antifouling activities when exposed to diverse and complex biological environments over extended time is vital for development more effective medical devices and diagnostics. Here, we describe a micrometer-thick, porous nanocomposite coating with both exceptional antifouling and electroconducting properties that greatly enhance the sensitivity of electrochemical sensors. Nozzle-assisted printing of oil-in-water emulsion is used to create a 1 micrometer thick coating composed of cross-linked albumin with interconnected pores, which also contains electroconducting gold nanowires. Using this approach, the antifouling conductive coating can be deposited only on the surface of the working electrode, and not on the reference and counter electrodes, which greatly facilitates the fabrication and functionality of multiplexed electrochemical sensors. The layer effectively resists biofouling and maintains rapid electron transfer kinetics for over one month when exposed directly to complex biological fluids, including serum and nasopharyngeal secretions. Compared to previously described thinner (nanometer thick) antifouling electroconductive coating made with drop casting or a spin coating of the same thickness, the nozzle-printed sensors coated with this thick porous nanocomposite exhibited sensitivities that were enhanced by 3.75- to 17-fold when three different target biomolecules were tested. As a result, emulsion-coated, multiplexed electrochemical sensors coated were able to carry out simultaneous detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid, antigen, and host antibody in clinical specimens with high sensitivity and specificity. This thick porous emulsion coating technology may provide a way to address hurdles currently restricting the application of electrochemical sensors for point-of-care (POC) diagnostic applications, as well as their use in implantable devices and other healthcare monitoring systems.
Label-free 3-D molecular imaging of living tissues using Raman Spectral Projection Tomography
Authors: Stepula Elzbieta , Walther Anders R. , Mehrotra Dev , Jensen Magnus , Yuan Mu H. , Pedersen Simon V. , Gentleman Eileen , Albro Michael B. , Hedegaard Martin A. B. , Bergholt Mads S. 
Published: September 2023

AbstractThe ability to image tissues in three-dimensions (3-D) with label-free molecular contrast at mesoscale would be a valuable capability in biology and biomedicine. Here, we introduce Raman spectral projection tomography (RSPT) for volumetric molecular imaging with sub-millimeter spatial resolution. We have developed a RSPT imaging instrument capable of providing 3-D molecular contrast in transparent and semi-transparent samples. A computational pipeline for multivariate reconstruction was established to extract label-free spatial molecular information from Raman projection data. We demonstrate imaging and visualization of phantoms of various complex shapes with label-free molecular contrast. Finally, we apply RSPT as a novel tool for imaging of molecular gradients and extracellular matrix heterogeneities in fixed and live tissue-engineered constructs and explanted native tissues. RSPT imaging opens new possibilities for label-free molecular monitoring of tissues.
Tuning of liver circadian transcriptome rhythms by thyroid hormone state in male mice
Authors: de Assis Leonardo Vinícius Monteiro , Harder Lisbeth , Lacerda José Thalles , Parsons Rex , Kaehler Meike , Cascorbi Ingolf , Nagel Inga , Rawashdeh Oliver , Mittag Jens , Oster Henrik 
Published: September 2023

ABSTRACTThyroid hormones (THs) are important regulators of systemic energy metabolism. In the liver, they stimulate lipid and cholesterol turnover and increase systemic energy bioavailability. It is still unknown how the TH state interacts with the circadian clock, another important regulator of energy metabolism. We addressed this question using a mouse model of hypothyroidism and performed circadian analyses. Low TH levels decreased locomotor activity, food intake, and body temperature mostly in the active phase. Concurrently, liver transcriptome profiling showed only subtle effects compared to elevated TH conditions. Comparative circadian transcriptome profiling revealed alterations in mesor, amplitude, and phase of transcript levels in the livers of low-TH mice. Genes associated with cholesterol uptake, biosynthesis, and bile acid secretion showed reduced mesor. Increased and decreased cholesterol levels in the serum and liver were identified, respectively. Combining data from low- and high-TH conditions allowed the identification of 516 genes with mesor changes as molecular markers of the liver TH state. These genes participate in many known TH-associated processes. We further explored these genes and created a unique expression panel that can assess liver TH state in a time-of-day dependent manner. Our findings suggest that the liver has a low TH state under physiological conditions. Circadian profiling reveals genes as potential markers of liver TH state in one-time point studies.
Improved CAR-T cell activity associated with increased mitochondrial function primed by galactose
Authors: Gross Golda , Alkadieri Suha , Meir Amilia , Itzhaki Orit , Aharony-Tevet Yarden , Yosef Shahar Ben , Zenab Angi , Shbiro Liat , Toren Amos , Yardeni Tal , Jacoby Elad 
Published: September 2023

AbstractCD19 CAR-T cells have led to durable remissions in patients with refractory B-cell malignancies; nevertheless, most patients eventually relapse in the long term. Many interventions aimed at improving current products have been reported, with a subset of them focusing on a direct or indirect link to the metabolic state of the CAR-T cells. We assessed clinical products from an ongoing clinical trial utilizing CD19-28z CAR-T cells from patients with acute lymphoblastic leukemia. CAR-T clinical products leading to a complete response had significantly higher mitochondrial function (by oxygen consumption rate) irrespective of mitochondrial content. Next, we replaced the carbon source of the media from glucose to galactose to impact cellular metabolism. Galactose-containing media increased mitochondrial activity in CAR-T cells, and improvedin vitroefficacy, without any consistent phenotypic change in memory profile. Finally, CAR-T cells produced in galactose-based glucose-free media resulted in increased mitochondrial activity. Using anin vivomodel of Nalm6 injected mice, galactose-primed CAR-T cells significantly improved leukemia-free survival compared to standard glucose-cultured CAR-T cells. Our results prove the significance of mitochondrial metabolism on CAR-T cell efficacy and suggest a translational pathway to improve clinical products.
Application of the Sepsis-3 criteria to describe sepsis epidemiology in the Amsterdam UMCdb intensive care dataset
Authors: Williams Christopher YK , Edinburgh Tom , Elbers Paul WG , Thoral Patrick J , Ercole Ari 
Published: September 2023

AbstractIntroductionSepsis is a major cause of morbidity and mortality worldwide. In the updated, 2016 Sepsis-3 criteria, sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, where organ dysfunction can be represented by an increase in the Sequential Organ Failure Assessment (SOFA) score of 2 points or more. We sought to apply the Sepsis-3 criteria the characterise the septic cohort in the Amsterdam University Medical Centres database (Amsterdam UMCdb).MethodsWe examined adult intensive care unit (ICU) admissions in the Amsterdam UMCdb, which contains de-identified data for patients admitted to a mixed surgical-medical ICU at a tertiary academic medical centre in the Netherlands. We operationalised the Sepsis-3 criteria, defining organ dysfunction as an increase in the SOFA score of 2 points or more, while infection was defined as a new course of antibiotics or an escalation in antibiotic therapy, with at least one antibiotic given intravenously. Patients with sepsis were determined to be in septic shock if they additionally required the use of vasopressors and had a lactate level >2 mmol/L.ResultsWe identified 18,221 ICU admissions from 16,408 patients in our cohort. There were 6,371 unique sepsis episodes, of which 30.1% met the criteria for septic shock. A total of 4,958/6,371 sepsis (77.8%) episodes occurred on ICU admission. Forty-eight percent of emergency medical admissions and 37.0% of emergency surgical admissions were for sepsis. Overall, there was a 12.5% ICU mortality rate; patients with septic shock had a higher ICU mortality rate (38.5%) than those without shock (11.3%).ConclusionsWe successfully operationalised the Sepsis-3 criteria to the Amsterdam UMCdb, allowing the characterization and comparison of sepsis epidemiology across different centres.
Combination of QTL and GWAS to uncover the role of phosphodiesterases in ischemic heart disease
Authors: Xiao Jun , Gao Ziting , Wei Hongye , Wei Yajing , Qiu Ziyi , Huang Wuqing 
Published: September 2023

AbstractBackgroundPhosphodiesterases (PDEs) are regarded as important therapeutic targets for multiple diseases, and the cardiovascular benefits of several PDE inhibitors have received extensive interests.ObjectivesTo explore the relationship between genetically-predicted PDEs and ischemia heart disease via drug target Mendelian Randomization (MR) approach.MethodsThe expression of genes encoding PDEs was used to proxy the level of PDEs, and available quantitative trait loci of gene expression and DNA methylation (eQTLs and mQTLs) for each target gene were identified as the genetic instruments. Coronary heart disease (CHD) and myocardial infarction (MI) were the outcomes. Summary-data-based MR method was used to generate the estimates and two-step MR analysis was applied to investigate the mediation of metabolic traits.ResultsMR analyses identified two types of PDEs, PDE5 and PDE8, genetically-predicted expression in blood of the encoded genes was significantly associated with the risk of CHD (ORPDE5A=1.22,95% CI=1.06-1.40; ORPDE8A=1.26,95% CI=1.07-1.49) and MI (ORPDE5A=1.27,95% CI=1.09-1.48; ORPDE8A=1.24,95% CI=1.04-1.48). Especially, the highest expression of PDE5A was observed in artery aorta, which was also positively related to CHD (OR=1.17,95% CI=1.05-1.32) and MI (OR=1.15,95% CI=1.02-1.30). Besides, the methylation level of 12 CpG sites showed a relation with CHD or MI via affecting PDE5A expression. The observed association between PDE5A expression and outcomes were partly mediated by blood pressure and LDL cholesterol, and the association with MI were mostly mediated by CHD (Proportion-mediated: 78.84%).ConclusionsThis study provided genetic evidence about the protective role of PDE5 inhibition against ischemic heart disease, especially in preventing patients with CHD from developing MI.
Flamingo participates in multiple models of cell competition
Authors: Bosch Pablo Sanchez , Cho Bomsoo , Axelrod Jeffrey D. 
Published: September 2023

AbstractThe growth and survival of cells with different fitness, such as those with a proliferative advantage or a deleterious mutation, is controlled through cell competition. During development, cell competition enables healthy cells to eliminate less fit cells that could jeopardize tissue integrity, and facilitates the elimination of pre-malignant cells by healthy cells as a surveillance mechanism to prevent oncogenesis. Malignant cells also benefit from cell competition to promote their expansion. Despite its ubiquitous presence, the mechanisms governing cell competition, particularly those common to developmental competition and tumorigenesis, are poorly understood. Here, we show that inDrosophila, the planar cell polarity (PCP) protein Flamingo (Fmi) is required by winners to maintain their status during cell competition in malignant tumors to overtake healthy tissue, in early pre-malignant cells when they overproliferate among wildtype cells, in healthy cells when they later eliminate pre-malignant cells, and by supercompetitors as they compete to occupy excessive territory within wildtype tissues. “Would-be” winners that lack Fmi are unable to over-proliferate, and instead become losers. We demonstrate that the role of Fmi in cell competition is independent of PCP, and that it uses a distinct mechanism that may more closely resemble one used in other less well-defined functions of Fmi.
Sex differences in dispersal predict sex differences in helping across cooperative birds and mammals
Authors: Fenner Patrick , Currie Thomas E. , Young Andrew J. 
Published: September 2023

ABSTRACTSex differences in cooperation are widespread, but their evolution remains poorly understood. Here we use phylogenetic comparative methods to test the Dispersal hypothesis for the evolution of sex differences in contributions to cooperative care across the cooperatively breeding birds and mammals. The Dispersal hypothesis predicts that, where non-breeding individuals of both sexes help to rear offspring within their natal group, the more dispersive sex will contribute less (either because leaving the natal group earlier reduces the downstream direct benefit from cooperation or because dispersal activities trade-off against cooperation). Our analyses reveal (i) support for the Dispersal hypothesis (sex biases in dispersal predict sex biases in natal cooperation across taxa), and (ii) that this pattern cannot be readily attributed to alternative hypothesized drivers of sex differences in cooperation (kin selection, heterogamety, paternity uncertainty, patterns of parental care or differences between birds and mammals). Our findings help to clarify the evolutionary drivers of sex differences in cooperation and highlight the need for single-species studies to now tease apart whether sex differences in dispersal predict sex differences in natal cooperation because dispersal impacts the direct benefits of natal cooperation (as is often proposed) or because activities that promote dispersal trade-off against natal cooperation.
The role of phages in proglacial stream biofilm communities characterized by microdiversity
Authors: Peter Hannes , Michoud Gregoire , Bhanu Busi Susheel , Battin Tom J. 
Published: September 2023

AbstractViruses modulate the diversity and activity of microbial communities. However, little is known about their role for the structure of stream biofilms communities. Here, we present insights into the diversity and composition of viral communities in various streams draining three proglacial floodplains in Switzerland. Proglacial streams are characterized by extreme environmental conditions, including near-freezing temperatures and ultra-oligotrophy. These conditions select for few but well-adapted bacterial clades, which dominate biofilm communities and occupy niches via microdiversification. We used metagenomic sequencing to reveal a remarkably diverse biofilm virome in these streams. Across the different floodplains and streams, viral community composition was tightly coupled to that of the bacterial hosts, which was underscored by generally high host specificity. Combining predictions of phage-host interactions with auxiliary metabolic genes (AMGs), we identify specific AMGs shared by phages infecting microdiverse clade members. Our work provides a step towards a better understanding of the complex interactions among bacteria and phages in stream biofilm communities in general and streams influenced by glacier meltwaters and characterized by microdiversity in particular.
Visual feature tuning properties of short-latency stimulus-driven ocular position drift responses during gaze fixation
Authors: Khademi Fatemeh , Zhang Tong , Baumann Matthias P. , Malevich Tatiana , Yu Yue , Hafed Ziad M. 
Published: September 2023

AbstractOcular position drifts during gaze fixation are generally considered to be random walks. However, we recently identified a short-latency ocular position drift response, of approximately 1 min arc amplitude, that is triggered within <100 ms by visual onsets. This systematic eye movement response is feature-tuned and seems to be coordinated with a simultaneous resetting of the saccadic system by visual stimuli. However, much remains to be learned about the drift response, especially for designing better-informed neurophysiological experiments unraveling its mechanistic substrates. Here we systematically tested multiple new feature tuning properties of drift responses. Using highly precise eye tracking in three male rhesus macaque monkeys, we found that drift responses still occur for tiny foveal visual stimuli. Moreover, the responses exhibit size tuning, scaling their amplitude as a function of stimulus size, and they also possess a monotonically increasing contrast sensitivity curve. Importantly, short-latency drift responses still occur for small peripheral visual targets, which additionally introduce spatially-directed modulations in drift trajectories towards the appearing peripheral stimuli. Drift responses also remain predominantly upward even for stimuli exclusively located in the lower visual field, and even when starting gaze position is upward. When we checked the timing of drift responses, we found that it was better synchronized to stimulus-induced saccadic inhibition timing than to stimulus onset. These results, along with a suppression of drift response amplitudes by peri-stimulus saccades, suggest that drift responses reflect the rapid impacts of short-latency and feature-tuned visual neural activity on final oculomotor control circuitry in the brain.SignificanceDuring gaze fixation, the eye drifts slowly in between microsaccades. While eye position drifts are generally considered to be random eye movements, we recently found that they are modulated with very short latencies by some stimulus onsets. Here we characterized the feature-tuning properties of such stimulus-driven drift responses. Our results demonstrate that drift eye movements are not random, and that visual stimuli can impact them in a manner similar to how such stimuli impact microsaccades.
Unveiling the Holliday junction conformational dynamics of upon binding with DNA architectural proteins IHF; A Single molecule FRET approach
Authors: Islam Farhana , Mishra Padmaja P. 
Published: September 2023

AbstractIntegration host factor (IHF) ofE. coliis a nucleoid-associated protein with diverse roles in DNA packaging, viral DNA integration, and recombination. IHF binds to duplex DNA containing a 13 bp consensus sequence with nanomolar affinity and induces a significant bend of approximately 160° upon binding. While the Wild type IHF (WtIHF) is involved in DNA bending, thereby facilitating the integration of foreign DNA into the host genome, its engineered version, Single chain IHF (ScIHF) was designed for specific genetic engineering and biotechnological applications. We investigated interaction of the two IHF variants with Holliday junctions (HJ), crucial intermediates in DNA repair and homologous recombination. Our finding demonstrate that both variant of IHF binds to HJs with high affinity in presence of the consensus sequence, indicating a structure-based recognition mechanism. HJs are dynamic structures that can adopt open or stacked conformation. The open conformation facilitates processes like branch migration and strand exchange. Through quantitative binding studies using microscale thermophoresis, we determined the binding of IHF to four-way DNA junctions that harboured two specific binding sequences H’ & H1. Circular dichroism (CD) experiments revealed the protein’s impact on the junction conformation. This was further confirmed by Single molecule Förster resonance energy transfer (smFRET) technique that was used to examine the binding of IHF to the junction and its effect on the dynamicity of junction conformation. We also probed the population distribution of junction conformations. Interestingly, our results revealed that binding of both WtIHF & ScIHF shifts the population towards the open conformation of the junction and stabilised it in that conformation. In summary, our findings demonstrate that IHF binds HJs with a strong affinity and has a stabilizing effect on maintaining the junction’s open conformation.
The role of urban green spaces in supporting active and healthy ageing: an exploration of behaviour–physical setting–gender correlations
Authors: Ye Xi , Ren Xuan , Shang Yuanzheng , Liu Jiayu , Feng Huangyu , Zhang Yun 
Published: September 2023

PurposeUrban green spaces support people to approach active, healthy ageing, especially in high-density cities where they compensate for limited private living spaces. This research paper aims to examine how urban green spaces support active, healthy ageing by exploring correlations between behaviour, physical setting and gender difference among older people in a highly populated urban context.Design/methodology/approachUrban parks in older neighbourhoods of Macau were selected for data collection. Photographic documentation was used to collect data, with 1,201 older people photographed identified as valid samples. Each was coded according to labels of behaviour, physical setting and gender. Chi-squared tests were conducted to assess correlations between behaviours and features of physical settings, and differences between genders in behaviours and physical settings. Logistic regression analysis was conducted to further examine associations between older people's behaviours and features of physical settings by gender.FindingsThe research reveals types and frequency of behaviours displayed, preferred environmental features for different behaviours and gender differences in behaviours and preferred environmental features. Design principles targeting active, healthy ageing should consider particular amenities and street furniture, the arrangement of trees and landscapes and the integration of open and secluded places.Originality/valuePrevious studies address older people's behaviour from the perspective of either environmental influence or gender difference, but there have been few studies on gendered behavioural differences among older people in urban green spaces. Analysing the behaviour–physical setting–gender relationship provides more evidence in the field of built environment studies.