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The purpose of the current study was to identify biopsychosocial factors associated with depressive symptoms among Hispanic women aged ≥50 years. Cross-sectional data related to 10 biological, psychological, and social factors were analyzed. Center for Epidemiologic Studies Depression Scale scores suggested that 32% of the sample had depressive symptoms. Self-esteem, self-perception of health status, income, and chronic pain had statistically significant associations with depressive symptoms. A logistic regression analysis showed that increasing self-esteem scores were associated with decreases in the likelihood of having depressive symptoms. Findings underscore that depression is associated with biological, psychological, and social factors. Culturally tailored interventions that aim at targeting these factors may have an impact on Hispanic women's depression and overall well-being. [ Journal of Psychosocial Nursing and Mental Health Services, xx (x), xx–xx.]

Background: New era of cardiac surgery aims to provide an enhanced postoperative recovery through the implementation of every step of the process. Thus, perfusion strategy should adopt evidence-based measures to reduce the impact of cardiopulmonary bypass (CPB). Hematic Antegrade Repriming (HAR) provides a standardized procedure combining several measures to reduce haemodilutional priming to 300 mL. Once the safety of the procedure in terms of embolic release has been proven, the evaluation of its beneficial effects in terms of transfusion and ICU stay should be assessed to determine if could be considered for inclusion in Enhanced Recovery After Cardiac Surgery (ERACS) programs. Methods: Two retrospective and non-randomized cohorts of high-risk patients, with similar characteristics, were assessed with a propensity score matching model. The treatment group (HG) (n = 225) received the HAR. A historical cohort, exposed to conventional priming with 1350 mL of crystalloid confirmed the control group (CG) (n = 210). Results: Exposure to any transfusion was lower in treated (66.75% vs. 6.88%, p 10 h) (26.51% vs. 12.62%; p 2 d) (47.47% vs. 31.19%; p Discussion: By reducing the gaseous and crystalloid emboli during CPB initiation, HAR seems to have a beneficial impact on recovery and reduces the overall transfusion until discharge, leading to significant cost savings per process. Due to the preliminary and retrospective nature of the research and its limitations, our findings should be validated by future prospective and randomized studies.

The COVID-19 pandemic brought drastic changes in people’s daily routines, but their ability to be resilient from this life- altering event varies. This makes religious orientation one of the indicators of an individual's resiliency, as it fosters spiritual stability and protects people from distress during the crisis. This study aims to measure the level of religious orientation among Roman Catholics, Evangelical Christians, Baptists, and Seventh Day Adventists in facing the struggles of COVID-19. Additionally, it investigates the level of resiliency among the respondents. This study also examines if there is a significant relationship between religious orientation and resiliency. Lastly, it determines if there is a significant difference in the level of religious orientation when analyzed by the type of religion. Using the quota sampling technique, 427 residents of Davao City aged 18 years old and above and affiliated with the aforementioned religions were surveyed. This study uses descriptive correlational design to find any existing significant relationship between religious orientation and resiliency. This paper adapts Allport-Ross Religious Orientation Scale (ROS) and Personal Resilience Assessment Questionnaire as the research instruments. The result of this study reveals that there is insufficient evidence to support a significant relationship between religious orientation and level of resiliency. Furthermore, the researchers recommend performing more in-depth studies investigating religious orientation and resiliency in the face of other meaningful life-changing events.

Introduction: Post Transplant patients experience a great variety of cerebrovascular (CV) complications including ischemic stroke (IS), TIA, SAH, ICH, and posterior reversible encephalopathy syndrome (PRES). These increase mortality & morbidity in an already susceptible population but the incidence of these complications, risk factors, and outcomes in transplant recipients have not been examined in detail. Methods: Design: A retrospective observational study. Population: Patients >18 years of age who underwent solid organ transplantation since 2012 at a tertiary care center. Patients were divided into 2 groups, with CV complications and without. Outcomes of interest were the proportion of CV complications, length of stay (LOS), discharge disposition, functional outcomes (defined by a mRS), and survival time post-transplant. Results: A total of 94 patients met the inclusion criteria (31% (n=29) with CV complications vs 69% (n=65) patients without). The median age was 57.5 years (51.41 vs 45.75 p>0.05). IS was the most prevalent CV complication (n=13, 44%, most common etiology was cryptogenic 76.9% (n=11)) followed but ICH (n=6, 20%), and most of CV complications occurred within 1 year post-transplant (n=17, 58.6%). Patients with past history of TIA or stroke were more likely to have a CV complication post-transplant (OR 0.66 vs 4.89, p=0.05) but there was no significance for the other cardiovascular risk factors when compared to transplant recipients with no complications. Patients with complications were more likely to have lung transplants (p0.05). Conclusions: Post-transplant patients, especially lung transplants, have a high incidence of CV complications including stroke and higher case fatality. There was an association between a history of TIA or IS and subsequent CV events in our patient population. We did not demonstrate any difference in LOS, demographical characteristics, use of antithrombotic, or length of survival post-transplant in both the groups.

Flare frequency distributions represent a key approach to addressing one of the largest problems in solar and stellar physics: determining the mechanism that counter-intuitively heats coronae to temperatures that are orders of magnitude hotter than the corresponding photospheres. It is widely accepted that the magnetic field is responsible for the heating, but there are two competing mechanisms that could explain it: nanoflares or Alfv\'en waves. To date, neither can be directly observed. Nanoflares are, by definition, extremely small, but their aggregate energy release could represent a substantial heating mechanism, presuming they are sufficiently abundant. One way to test this presumption is via the flare frequency distribution, which describes how often flares of various energies occur. If the slope of the power law fitting the flare frequency distribution is above a critical threshold, $\alpha=2$ as established in prior literature, then there should be a sufficient abundance of nanoflares to explain coronal heating. We performed $>$600 case studies of solar flares, made possible by an unprecedented number of data analysts via three semesters of an undergraduate physics laboratory course. This allowed us to include two crucial, but nontrivial, analysis methods: pre-flare baseline subtraction and computation of the flare energy, which requires determining flare start and stop times. We aggregated the results of these analyses into a statistical study to determine that $\alpha = 1.63 \pm 0.03$. This is below the critical threshold, suggesting that Alfv\'en waves are an important driver of coronal heating., Comment: 1,002 authors, 14 pages, 4 figures, 3 tables, published by The Astrophysical Journal on 2023-05-09, volume 948, page 71

The most alarming aspect of the Sudanese toombak smokeless tobacco is that it contains high levels of highly toxic tobacco-specific nitrosamines (TSNAs). Understanding the microbiology of toombak is of relevance because TSNAs are an indirect result of microbial-mediated nitrate reductions. We conducted shotgun metagenomic sequencing on a toombak product for which relevant features are presented here. The microbiota was composed of over 99% Bacteria. The most abundant taxa included Actinobacteria, specifically the genera Enteractinococcus and Corynebacterium, while Firmicutes were represented by the family Bacillaceae and the genus Staphylococcus. Selected gene targets were nitrate reduction and transport, antimicrobial resistance, and other genetic transference mechanisms. Canonical nitrate reduction and transport genes (i.e. nar) were found for Enteractinococcus and Corynebacterium while various species of Staphylococcus exhibited a notable number of antimicrobial resistance and genetic transference genes. The nitrate reduction activity of the microbiota in toombak is suspected to be a contributing factor to its high levels of TSNAs. Additionally, the presence of antimicrobial resistance and transference genes could contribute to deleterious effects on oral and gastrointestinal health of the end user. Overall, the high toxicity and increased incidences of cancer and oral disease of toombak users warrants further investigation into the microbiology of toombak.

Background: Many stresses trigger cellular senescence, including telomere shortening, oncogene activation, DNA-replication stress, oxidative stress, and resistance to apoptosis. Forkhead box protein O4 (FOXO4) plays a pivotal role in cellular senescence, by binding to and inactivating p53, thereby leading to cellular senescence and inhibiting p53 mediated apoptosis. As a result, misregulation of FOXO4-p53 is linked to numerous diseases including cancers and aging-related diseases, pulmonary fibrosis and neurodegenerative diseases. Targeting of the FOXO4-p53 interface has been accomplished using a synthetic D retro inverse peptide (DRI), however recognition of the key molecular drivers of the interactions remains unknown. Understanding these interactions on a molecular level could lead to the development of small compounds, with enhanced pharmacological qualities, such as high stability, membrane permeability, and oral bioavailability, that mimics the activity of the DRI peptide. Methods and Results: Using an in silico model of the FOXO4-p53 interaction, we designed shorter peptides within the DRI to identify the key interactions. A biophysical assay demonstrates these shorter peptides retain strong binding affinity to p53, suggesting that the DRI's hot spot is located within these peptides. Conclusions: Taken together, this data provides information at the molecular level that is key to understanding the interplay of two proteins responsible for cellular senescence and provides the basis for the design of small molecules to inhibit this interaction.

A systematic study on the influence of fillers on the structural properties at micro and nanoscale of vulcanized compounds based on a natural rubber matrix reinforced with silica and/or carbon black is presented. Several compounds with different SiO2/CB ratios (1.5/1, 2.25/1, and 3/1) and total filler contents (55, 60, and 65 phr) were prepared and vulcanized at 150 °C. The experimental techniques used were rheometric, swelling and dynamic mechanical tests, and positron lifetime spectroscopy. From these techniques, cure reaction parameters, the fraction at the maximum degree of swelling, storage modulus, loss tangent, and fractional free volume were measured. Using a recent model based on a hydrodynamic description and the percolation of aggregates in a rubber matrix, it was found that regardless of the filler combinations, the dynamic storage modulus is well represented as a function of the filler volume fraction. Besides, beyond a critical SiO2/CB ratio (2.25/1) in the formulations of the compounds, the loss tangent does not depend on the SiO2/CB ratio. The results obtained show a direct correlation among mechanical properties, swelling and fractional free volume, and the type and amount of fillers in the reinforced compounds.

While astrocytes are known to be important for development and nourishment of the nervous system, the field is just beginning to explore how astrocytes respond to environmental stimuli. UsingCaenorhabditis elegansand their astrocyte-equivalent, CEPsh, we asked whether astrocyte-like glia respond to odor exposure. We found one day-old adultC. elegansdecreasehlh-17promoter (CEPsh glia marker) mediated fluorescent expression when trained with an innately attractive odor butanone. Moreover, the olfactory training paradigm itself affects phlh-17expression, but in a different way. This suggests astrocyte-like CEPsh glia can integrate environmental information to respond to changes in the environment, which enhances survival.

The manuscript discusses recent advances on computer-aided drug discovery (CADD) with focus on data-dependent drug discovery. Herein, we do not intend to review the many CADD methodologies comprehensively. Instead, the review discusses progress on selected concepts, methodologies, resources, and applications that are part of multidisciplinary efforts: the manuscript covers advances in artificial intelligence, machine learning, virtual screening, and chemical space including the concept of chemical multiverses, and novel extended similarity methods for chemical space exploration. Throughout the review, we emphasize public resources and open-source code available to the scientific community working in academia and non-profit institutions.

In bacteria, mutations lead to the evolution of antibiotic resistance, which is one the main public health problems of the 21stcentury. Therefore, determining which cellular processes most frequently contribute to mutagenesis, especially in cells that have not been exposed to exogenous DNA damage, is critical. Here, we show that endogenous oxidative stress is a key driver of mutagenesis and the subsequent development of antibiotic resistance. This is the case for all classes of antibiotics tested and across highly divergent species, including patient-derived strains. We show that the transcription-coupled repair pathway, which uses the nucleotide excision repair proteins (TC-NER), is responsible for endogenous oxidative stress-dependent mutagenesis and subsequent evolution. This strongly suggests that a majority of mutations arise through transcription-associated processes rather than the replication fork. In addition to determining that the NER proteins play a critical role in mutagenesis and evolution, we also identify the DNA polymerases responsible for this process. Our data strongly suggest that cooperation between three different mutagenic DNA polymerases, likely at the last step of TC-NER, is responsible for mutagenesis and evolution. Overall, our work identifies that a highly conserved pathway drives mutagenesis due to endogenous oxidative stress, which has broad implications for all diseases of evolution, including antibiotic resistance development.

Software defect prediction is an important area in software engineering because it helps developers identify and fix problems before they become costly and hard-to-fix bugs. Early detection of software defects helps save time and money in the software development process and ensures the quality of the final product. This research aims to evaluate three algorithms to build Bayesian Networks to classify whether a project is prone to defects. The choice is based on the fact that the most used approach in the literature is Naive Bayes, but no works use Bayesian Networks. Thus, K2, Hill Climbing, and TAN are used to construct Bayesian Networks. On the other hand, three public PROMISE data sets are used based on McCabe and Halstead complexity metrics. The results are compared with the most used approaches in the literature, such as Decision Tree and Random Forest. The results from different performance metrics applied to a cross-validation process show that the classification results are comparable to Decision Tree and Random Forest, with the advantage that Bayesian algorithms show less variability, which helps engineering software to have greater robustness in their predictions since the selection of training and test data do not give variable results, unlike Decision Tree and Random Forest.

The development of simple, efficient, and robust strategies affording the facile construction of biomimetic organocatalytic nano-objects is currently a subject of great interest. Herein, a new pathway to artificial organocatalysts based on partially collapsed individual soft nano-objects displaying useful and diverse biomimetic catalytic functions is reported. Single-chain polymer nanoparticles endowed with enzyme-mimetic activity synthesized following this new route display (i) a relatively extended morphology under good solvent conditions, as revealed by small angle neutron scattering and coarse-grained molecular dynamics simulation results, (ii) multiple, compartmentalized, and accessible catalytic sites in which borane catalytic units are retained via B···O interactions, and (iii) unprecedented reductase and polymerase enzyme-mimetic properties. © 2013 American Chemical Society., Financial support from the projects MAT2012-31088 (MINECO) and IT-654-13 (GV) is acknowledged. I. P.-B. acknowledges CSIC for her JAE-PREDOC grant. This work is based on has been supported by the European Commission under the 7th Framework Programme through the 'Research Infrastructures' action of the 'Capacities' Programme, NMI3-II Grant number 283883.

Despite centuries-long use of

Smokeless tobacco products (STP) contain bacteria, mold, and fungi due to exposure from surrounding environments and tobacco processing. This has been a cause for concern since the presence of microorganisms has been linked to the formation of highly carcinogenic tobacco-specific nitrosamines. These communities have also been reported to produce toxins and other pro-inflammatory molecules that can cause mouth lesions and elicit inflammatory responses in STP users. Moreover, microbial species in these products could transfer to the mouth and gastrointestinal tract, potentially altering the established respective microbiotas of the consumer. Here, we present the first metagenomic analysis of select smokeless tobacco products, specifically US domestic moist and dry snuff. Bacterial, eukaryotic, and viral species were found in all tobacco products where 68% of the total species was comprised of Bacteria with 3 dominant phyla but also included 32% Eukarya and 1% share abundance for Archaea and Viruses. Furthermore, 693,318 genes were found to be present and included nitrate and nitrite reduction and transport enzymes, antibiotic resistance genes associated with resistance to vancomycin, β-lactamases, their derivatives, and other antibiotics, as well as genes encoding multi-drug transporters and efflux pumps. Additional analyses showed the presence of endo- and exotoxin genes in addition to other molecules associated with inflammatory responses. Our results present a novel aspect of the smokeless tobacco microbiome and provide a better understanding of these products' microbiology. KEY POINTS: • The findings presented will help understand microbial contributions to overall STP chemistries. • Gene function categorization reveals harmful constituents outside canonical forms. • Pathway genes for TSNA precursor activity may occur at early stages of production. • Bacteria in STPs carry antibiotic resistance genes and gene transfer mechanisms.

The bacterial exoenzyme C3 transferase (C3) irreversibly inhibits RhoA GTPase leading to stimulation of axonal outgrowth in injured neurons. C3 has been used successfully in models of neurotrauma and shows promise as an option to support cell survival and axonal growth of dopaminergic neurons in Parkinson’s disease cell therapy. Whether the continuous expression of C3 in dopaminergic neurons is well-tolerated is unknown. To assess the potential neurotoxicity of sustained expression of C3 in dopaminergic neurons, we generated Cre recombinase-dependent adeno-associated viral vectors (AAV) for targeted C3 delivery to dopaminergic neurons of the mouse substantia nigra pars compacta (SNc). The effect of continuous expression of C3 on dopaminergic neurons was assessed by immunohistochemistry and compared to that of enhanced yellow fluorescent protein (EYFP) as negative controls. We did not find significant reduction of tyrosine hydroxylase expression levels nor the presence of cleaved activated caspase 3. Astrocytic activation as determined by GFAP expression was comparable to EYFP controls. To evaluate the impact of C3 expression on striatal terminals of the nigrostriatal pathway, we compared the rotational behavior of wildtype mice injected unilaterally with either C3 or 6-hydroxydopamine (6-OHDA). Mice injected with C3 exhibited similar ipsiversive rotations to the site of injection in comparison to control mice injected with EYFP and significantly fewer ipsiversive rotations compared to 6-OHDA lesioned mice. Non-significant difference between C3 and EYFP controls in behavioral and histological analyses demonstrate that transduced dopaminergic neurons express C3 continuously without apparent adverse effects, supporting the use of C3 in efficacy studies targeting dopaminergic neurons.

Introduction Cancer stem cells (CSCs) drive the initiation, maintenance, and therapy response of breast tumors. CD49f is expressed in breast CSCs and functions in the maintenance of stemness. Thus, blockade of CD49f is a potential therapeutic approach for targeting breast CSCs. In the present study, we aimed to repurpose drugs as CD49f antagonists. Materials and methods We performed consensus molecular docking using a subdomain of CD49f that is critical for heterodimerization and a collection of pharmochemicals clinically tested. Molecular dynamics simulations were employed to further characterize drug-target binding. Using MDA-MB-231 cells, we evaluated the effects of potential CD49f antagonists on 1) cell adhesion to laminin; 2) mammosphere formation; and 3) cell viability. We analyzed the effects of the drug with better CSC-selectivity on the activation of CD49f-downstream signaling by Western blot (WB) and co-immunoprecipitation. Expressions of the stem cell markers CD44 and SOX2 were analyzed by flow cytometry and WB, respectively. Transactivation of SOX2 promoter was evaluated by luciferase reporter assays. Changes in the number of CSCs were assessed by limiting-dilution xenotransplantation. Results Pranlukast, a drug used to treat asthma, bound to CD49f in silico and inhibited the adhesion of CD49f+ MDA-MB-231 cells to laminin, indicating that it antagonizes CD49f-containing integrins. Molecular dynamics analysis showed that pranlukast binding induces conformational changes in CD49f that affect its interaction with β1-integrin subunit and constrained the conformational dynamics of the heterodimer. Pranlukast decreased the clonogenicity of breast cancer cells on mammosphere formation assay but had no impact on the viability of bulk tumor cells. Brief exposure of MDA-MB-231 cells to pranlukast altered CD49f-dependent signaling, reducing focal adhesion kinase (FAK) and phosphatidylinositol 3-kinase (PI3K) activation. Further, pranlukast-treated cells showed decreased CD44 and SOX2 expression, SOX2 promoter transactivation, and in vivo tumorigenicity, supporting that this drug reduces the frequency of CSC. Conclusion Our results support the function of pranlukast as a CD49f antagonist that reduces the CSC population in triple-negative breast cancer cells. The pharmacokinetics and toxicology of this drug have already been established, rendering a potential adjuvant therapy for breast cancer patients.

Based on prior knowledge and with the support of new methodology, solid progress in the understanding of seed life has taken place over the few last years. This update reflects recent advances in three key traits of seed life (i.e., preharvest sprouting, genomic imprinting, and stored-mRNA). The first breakthrough refers to cloning of the mitogen-activated protein kinase-kinase 3 (MKK3) gene in barley and wheat. MKK3, in cooperation with ABA signaling, controls seed dormancy. This advance has been determinant in producing improved varieties that are resistant to preharvest sprouting. The second advance concerns to uniparental gene expression (i.e., imprinting). Genomic imprinting primarily occurs in the endosperm. Although great advances have taken place in the last decade, there is still a long way to go to complete the puzzle regarding the role of genomic imprinting in seed development. This trait is probably one of the most important epigenetic facets of developing endosperm. An example of imprinting regulation is polycomb repressive complex 2 (PRC2). The mechanism of PRC2 recruitment to target endosperm with specific genes is, at present, robustly studied. Further progress in the knowledge of recruitment of PRC2 epigenetic machinery is considered in this review. The third breakthrough referred to in this update involves stored mRNA. The role of the population of this mRNA in germination is far from known. Its relations to seed aging, processing bodies (P bodies), and RNA binding proteins (RBPs), and how the stored mRNA is targeted to monosomes, are aspects considered here. Perhaps this third trait is the one that will require greater experimental dedication in the future. In order to make progress, herein are included some questions that are needed to be answered.

In higher plants, the seed precursor (ovule primordia) is composed of three parts: funiculus, nucellus and chalaza, generating the latter one (II) or two (OI and II) protective maternal integuments (seed coat, SC). The appearance of a viable seed requires the coordinate growth and development of the preceding three compartments. Integuments are essentials for seed life as they nourish, protect and facilitate seed dispersion. Endosperm and integument growth and development are tightly coupled. Gymnosperm and angiosperm ovules are commonly unitegmic and bitegmic, respectively. Unusually, ategmy and threetegmy (OI, II and aril) also exist. The expression of theINO,ATSandETTgenes, involved in integument development, seems to have demonstrated that the fusion of OI and II leads to the appearance of unitegmy in higher plants. Likewise,INOexpression also manifests the conservation of OI during evolution. The molecular control of SC development is constituted by a signalling network with still a multitude of gaps. The fertilization-independent development of the ovule is repressed by the FERTILIZATION INDEPENDENT SEED (FIS), a Polycomb-Repressive-Complex-2 (PRC2). Both endosperm and SC development are tightly linked to PRC2 function. As in many other developmental processes, auxin plays an essential role during ovule and SC development. Auxin transport from the endosperm to the integuments is regulated by AGL62 (AGAMOUS-LIKE 62), the encoding gene of which is specifically expressed in the endosperm to suppress its cellularization. In the absence of AGL62 (i.e.agl62mutants), auxin remains trapped in the endosperm and the SC fails to develop (i.e. seed abortion). This update shows that auxin biosynthesis, transport and signalling play a predominant role and seem to be absolutely required in the pathway(s) that lead to SC formation, most likely not as a unique hormonal component.

Zygomycetes are ubiquitous saprophytes in natural environments which transform organic matter. Some zygomycetes of gender Mucor have attracted interest in health sector. Due to its ability as opportunistic microorganisms infecting immuno-compromised people and to the few available pharmacological treatments, the mucormycosis is receiving worldwide attention. Concerning to the pharmacological treatments, some triazole-based compounds such as fluconazole are extensively used. Nevertheless, we focused in the quinolines since they are broadly used models for the design and development of new synthetic antifungal agents. In this study, the fungistatic activity on M. circinelloides of various 2-aryl-4-aryloxyquinoline-based compounds was discovered, and in some cases, it resulted better than reference compound fluconazole. These quinoline derivatives were synthesized via the C

Given their safety and efficiency in protecting protein integrity, polysorbates (PSs) have been the most widely used excipients for the stabilization of protein therapeutics for years. In recent decades, however, there have been numerous reports about visible or sub-visible particles in PS-containing biotherapeutic products, which is a major quality concern for parenteral drugs. Alternative excipients that are safe for parenteral administration, efficient in protecting different protein drugs against various stress conditions, effective in protein stabilization in high-concentrated liquid formulations, stable under the storage conditions for the duration of the product’s shelf-life, and compatible with other formulation components and the primary packaging are highly sought after. The aim of this paper is to review potential alternative excipients from different families, including surfactants, carbohydrate- and amino acid-based excipients, synthetic amphiphilic polymers, and ionic liquids that enable protein stabilization. For each category, important characteristics such as the ability to stabilize proteins against thermal and mechanical stresses, current knowledge related to the safety profile for parenteral administration, potential interactions with other formulation components, and primary packaging are debated. Based on the provided information and the detailed discussion thereof, this paper may pave the way for the identification or development of efficient excipients for biotherapeutic protein stabilization.

It is known that data from both 16S and shotgun metagenomics studies are subject to biases that cause the observed relative abundances of taxa to differ from their true values. Model community analyses, in which the relative abundances of all taxa in the sample are known by construction, seem to offer the hope that these biases can be measured. However, it is unclear whether the bias we measure in a mock community analysis is the same as we measure in a sample in which taxa are spiked in at known relative abundance, or if the biases we measure in spike-in samples is the same as the bias we would measure in a real (e.g., biological) sample. Here, we consider these questions in the context of 16S rRNA measurements on three sets of samples: the commercially available Zymo cells model community; the Zymo model community mixed with Swedish Snus, a smokeless tobacco product that is virtually bacteria-free; and a set of commercially available smokeless tobacco products. Each set of samples was subject to four different extraction protocols. The goal of our analysis is to determine whether the patterns of bias observed in each set of samples are the same, i.e., can we learn about the bias in the commercially available smokeless tobacco products by studying the Zymo cells model community?

Single-chain nanoparticles (SCNPs) are a new class of macromolecular objects, synthesized through purely intramolecular cross-linking of single polymer chains. We use a multiscale hydrodynamics simulation approach to study, for the first time, SCNPs under shear flow. We investigate the case of irreversible SCNPs (permanent cross-links) in dilute solution. SCNPs emerge as a novel class of macromolecular objects with response to shear distinct from other systems such as linear chains, star polymers, rings, or dendrimers. This is evidenced by the observed set of scaling exponents for the shear rate dependence of the SCNP static and dynamic properties. Surprisingly, these exponents are, at most, marginally dependent on the specific topology of the SCNP (globular or sparse), suggesting that they are inherently related to the network-like character of the molecular architecture and not to its specific connectivity. At high Weissenberg numbers the dynamics of the sparse SCNPs is dominated by tumbling motion. Coexistence of tumbling and tank treading is observed for the most globular SCNPs., We acknowledge financial support from the projects MAT2015-63704-P (MINECO-Spain and FEDER-UE) and IT-654-13 (Basque Government, Spain).

The conformation of single-chain nanoparticles (SCNPs) in the presence of linear polystyrene crowding molecules has been studied by small-angle neutron scattering under contrast-matching of the crowders. A model describing the scattering of aggregating polydisperse SCNPs has been developed, resulting in the determination of the potentially squeezed size of the individual SCNPs within aggregates, their local chain statistics, and the average aggregation number, as a function of crowding. Two different crowders, of low and high molecular weights, are shown to have a different effect: while long chains tend to impede their aggregation above their overlap concentration, short ones are found to mediate depletion interactions leading to aggregation. Self-imposed crowding within the aggregates has a similar impact on chain conformation independently of the crowding of the surrounding medium. Our results are compared to recent simulations and shall contribute to the microscopic understanding of the phase behavior of soft intrinsically disordered nano-objects and in particular the effect of crowding on biomacromolecules., Funding by DIPC, the European Network of Excellence Softcomp, the Basque Government (code: IT1175-19), and the Ministerio de Ciencia, Innovación y Universidades [code: PGC2018-094548-B-I00 (MICINN/ FEDER, UE)] is gratefully acknowledged. This work is based on experiments performed at KWS-2 [Heinz Maier-Leibnitz Zentrum (MLZ), Garching, Germany] and has been supported by the European Commission under the 7th Framework Programme through the “Research Infrastructures” action of the “Capacities” Programme, NMI3-II Grant Number 283883.

Background: Major surgery is a term frequently used but poorly defined. The aim of the present study was to reach a consensus in the definition of major surgery within a panel of expert surgeons from the European Surgical Association (ESA). Methods: A 3-round Delphi process was performed. All ESA members were invited to participate in the expert panel. In round 1, experts were inquired by open- and closed-ended questions on potential criteria to define major surgery. Results were analyzed and presented back anonymously to the panel within next rounds. Closed-ended questions in round 2 and 3 were either binary or statements to be rated on a Likert scale ranging from 1 (strong disagreement) to 5 (strong agreement). Participants were sent 3 reminders at 2-week intervals for each round. 70% of agreement was considered to indicate consensus. Results: Out of 305 ESA members, 67 (22%) answered all the 3 rounds. Significant comorbidities were the only preoperative factor retained to define major surgery (78%). Vascular clampage or organ ischemia (92%), high intraoperative blood loss (90%), high noradrenalin requirements (77%), long operative time (73%) and perioperative blood transfusion (70%) were procedure-related factors that reached consensus. Regarding postoperative factors, systemic inflammatory response (76%) and the need for intensive or intermediate care (88%) reached consensus. Consequences of major surgery were high morbidity (>30% overall) and mortality (>2%). Conclusion: ESA experts defined major surgery according to extent and complexity of the procedure, its pathophysiological consequences and consecutive clinical outcomes.

Proteostasis dysfunction and activation of the unfolded protein response (UPR) are characteristic of all major neurodegenerative diseases. Nevertheless, although the UPR and proteostasis dysfunction has been studied in great detail in model organisms like yeast and mammalian cell lines, it has not yet been examined in neurons. In this study, we applied a viral vector-mediated expression of a reporter protein based on a UPR transcription factor, ATF4, and time-lapse fluorescent microscopy to elucidate how mouse primary neurons respond to pharmacological and genetic perturbations to neuronal proteostasis. In in vitro models of endoplasmic reticulum (ER) stress and proteasome inhibition, we used the ATF4 reporter to reveal the time course of the neuronal stress response relative to neurite degeneration and asynchronous cell death. We showed how potential neurodegenerative disease co-factors, ER stress and mutant α-synuclein overexpression, impacted neuronal stress response and overall cellular health. This work therefore introduces a viral vector-based reporter that yields a quantifiable readout suitable for non-cell destructive kinetic monitoring of proteostasis dysfunction in neurons by harnessing ATF4 signaling as part of the UPR activation.

In aqueous media, hydrophobic metallocorroles form nanoparticles that are potential theranostic anticancer agents. We have analyzed the electronic and Raman spectra of Al(III), Ga(III), and Au(III) corrole nanoparticles (and made comparisons with DFT-validated assignments of the IR spectra of corresponding monomers) in order to estimate the strengths of corrole-corrole electronic couplings in these assemblies. We find that these spectra are virtually unchanged upon aggregation, confirming that the intermolecular interactions in these nanoparticles are very weak.

In this work, TiO2 nanostructures (TiO2-NSs) were obtained at low temperature, using the sol–gel method, and their toxicity was evaluated in Swiss albino mice. For the synthesis, ethanol solvent was used and the concentration of the surfactant, cetyltrimethyl ammonium bromide (CTAB), was modified to determine its effect on the characteristics of the final product. Characterization of the synthesized TiO2-NSs was carried out using IR spectroscopy, X-ray diffraction (XRD), transmission (TEM) and scanning electron microscopy (SEM). The solids obtained, without heat treatment, showed an amorphous structure. When these were treated at 450 °C, they crystallized in an anatase type phase, independent of CTAB concentration, with a crystallite size of 3–5 nm. The particles showed a spheroidal or needle-like shape, with a nanometric size (100 nm), and formed spheroidal agglomerates (between 1 and 5 μm) or mesoporous structures, for the 6 mm concentration of CTAB. Additionally, the toxicity of the NSs synthesized was determined, using 3 mm CTAB and treated at 450 °C, giving doses of 5 mg/kg, 50 mg/kg, 300 mg/kg of TiO2-NSs to mice prepared for this test. The results of the analysis of the liver biopsies of the animals, on which euthanasia was practiced, showed that the best effect was the 300 mg/kg dose, where alterations in the mitochondria were observed, with distortion in their normal structure (fragmentation) and strong involvement of its outer membrane.

El artículo discute la noción de gobernanza algorítmica y de activismo de datos con ejemplos que ilustran la aparición de nuevos modelos de gobernanza en diferentes países. La selección y el análisis sucinto del discurso de proyectos específicos pretende ofrecer un panorama amplio que apoye y fomente la investigación y el debate sobre cómo se reposicionan las viejas asimetrías ligadas al ejercicio de la ciudadanía en la «era de los algoritmos».