High-confidence 3D template matching for cryo-electron tomography.

Visual proteomics attempts to build atlases of the molecular content of cells but the automated annotation of cryo electron tomograms remains challenging. Template matching (TM) and methods based on machine learning detect structural signatures of macromolecules. However, their applicability remains limited in terms of both the abundance and size of the molecular targets. Here we show that the performance of TM is greatly improved by using template-specific search parameter optimization and by including higher-resolution information. We establish a TM pipeline with systematically tuned parameters for the automated, objective and comprehensive identification of structures with confidence 10 to 100-fold above the noise level. We demonstrate high-fidelity and high-confidence localizations of nuclear pore complexes, vaults, ribosomes, proteasomes, fatty acid synthases, lipid membranes and microtubules, and individual subunits inside crowded eukaryotic cells. We provide software tools for the generic implementation of our method that is broadly applicable towards realizing visual proteomics.

Thinner is not always better: Optimizing cryo-lamellae for subtomogram averaging.

Cryo-electron tomography (cryo-ET) is a powerful method to elucidate subcellular architecture and to structurally analyze biomolecules in situ by subtomogram averaging, yet data quality critically depends on specimen thickness. Cells that are too thick for transmission imaging can be thinned into lamellae by cryo-focused ion beam (cryo-FIB) milling. Despite being a crucial parameter directly affecting attainable resolution, optimal lamella thickness has not been systematically investigated nor the extent of structural damage caused by gallium ions used for FIB milling. We thus systematically determined how resolution is affected by these parameters. We find that ion-induced damage does not affect regions more than 30 nanometers from either lamella surface and that up to ~180-nanometer lamella thickness does not negatively affect resolution. This shows that there is no need to generate very thin lamellae and lamella thickness can be chosen such that it captures cellular features of interest, thereby opening cryo-ET also for studies of large complexes.

Understanding and treating body image disturbances in eating disorders through body illusion interventions: a scoping review protocol.

BACKGROUND: We plan a scoping review aimed to synthesize what is known about the use of sensory-driven body illusion (BI) interventions for understanding and treating body image disturbance (BID) in people diagnosed with clinical eating disorders (EDs) and people with subclinical ED symptomatology. Our study will provide an outline of the current literature, identify gaps within the literature, and suggest novel directions for future research. METHODS/DESIGN: The scoping review process will be guided by the methodological framework of Arksey and O'Malley, subsequent recommendations by Levac et al., and the Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols Extension for Scoping Reviews guidelines. The following electronic databases will be systematically searched: MEDLINE (via PubMed), Web of Science, PsycINFO, and Scopus. Furthermore, to identify additional studies, we will use a search engine such as Google Scholar, and for grey literature, we will include Proquest for Dissertations and Theses. A search strategy has been identified and agreed upon by the research team in conjunction with a research librarian. Two researchers will screen the titles and abstracts independently and then assess the full text of the selected citations for the inclusion criteria. A third reviewer will be involved in cases of disagreement. Data will be extracted, collated, and charted to summarize all the relevant methods, outcomes, and key findings in the articles. DISCUSSION: A better understanding of this topic will aid in the development and refinement of current treatments aimed at treating BID in people with EDs. Implications and recommendations for research, policy, and practice in the context of the ED community will be discussed. SYSTEMATIC REVIEW REGISTRATION: https://osf.io/3bcm6/?view_only=83b2e8a2445d4266909992e3dfb51929.

Harnessing the post-vaccination era: Do emerging HPV types represent a new threat?

While the HPV vaccine is highly effective, it is unknown whether other, untargeted viral types could occupy empty niches to become an emerging threat. In this issue of Cell Host & Microbe, Pimenoff and colleagues present a community-level epidemiological analysis of HPV types up to 8 years after different vaccination policies.

Presence of Activated (Phosphorylated) STAT3 in Radiation Necrosis Following Stereotactic Radiosurgery for Brain Metastases.

Brain radiation necrosis (RN) is a subacute or late adverse event following radiotherapy, involving an exacerbated inflammatory response of the brain tissue. The risk of symptomatic RN associated with stereotactic radiosurgery (SRS) as part of the treatment of brain metastases (BMs) has been a subject of recent investigation. The activation of the signal transducer and activator of transcription 3 (STAT3) was shown in reactive astrocytes (RA) associated with BMs. Given that the pathophysiological mechanisms behind RN are not fully understood, we sought to investigate the role of STAT3 among other inflammatory markers in RN development. A mouse model of RN using clinical LINAC-based SRS was designed to induce brain necrosis with the administration of 50 Gy in a single fraction to the left hemisphere using a circular collimator of 5 mm diameter. Immunohistochemistry and multiplex staining for CD4, CD8, CD68, GFAP, and STAT3 were performed. For validation, eleven patients with BMs treated with SRS who developed symptomatic RN and required surgery were identified to perform staining for CD68, GFAP, and STAT3. In the mouse model, the RN and perinecrotic areas showed significantly higher staining for F4/80+ and GFAP+ cells, with a high infiltration of CD4 and CD8 T-lymphocytes, when compared to the non-irradiated cerebral hemisphere. A high number of GFAP+pSTAT3+ and F4/80+pSTAT3+ cells was found in the RN areas and the rest of the irradiated hemisphere. The analysis of human brain specimens showed that astrocytes and microglia were actively phosphorylating STAT3 in the areas of RN and gliosis. Phosphorylated STAT3 is highly expressed in the microglia and RA pertaining to the areas of brain RN. Targeting STAT3 via inhibition represents a promising strategy to ameliorate symptomatic RN in BM patients undergoing SRS.

An efficient triose phosphate synthesis and distribution in wheat provides tolerance to higher field temperatures.

High temperatures in the field hinder bread wheat high-yield production, mainly because of the adverse effects of heat over photosynthesis. The Yaqui Valley, the main wheat producer region in Mexico, is a zone prone to have temperatures over 30°C. The aim of this work was to test the flag leaf photosynthetic performance in 10 bread wheat genotypes grown under high temperatures in the field. The study took place during two seasons (2019-2020 and 2020-2021). In each season, control seeds were sown in December, while heat-stressed were sown in late January to subject wheat to heat stress (HS) during the grain-filling stage. HS reduced Grain yield from 20 to 58% in the first season. HS did not reduce chlorophyll content and light-dependent reactions were unaffected in any of the tested genotypes. Rubisco, chloroplast fructose 1,6-biphosphatase (FBPase), and sucrose phosphate synthase (SPS) activities were measured spectrophotometrically. Rubisco activity did not decrease under HS in any of the genotypes. FBPase activity was reduced by HS indicating that triose phosphate flux to starch synthesis was reduced, while SPS was not affected, and thus, sucrose synthesis was maintained. HS reduced aerial biomass in the 10 chosen genotypes. Genotypes SOKWB.1, SOKWB.3, and BORLAUG100 maintained their yield under HS, pointing to a potential success in their introduction in this region for breeding heat-tolerant bread wheat.

Comparative Analysis of Power Consumption between MQTT and HTTP Protocols in an IoT Platform Designed and Implemented for Remote Real-Time Monitoring of Long-Term Cold Chain Transport Operations.

IoT platforms for the transportation industry are portable with limited battery life and need real-time and long-term monitoring operations. Since MQTT and HTTP are widely used as the main communication protocols in the IoT, it is imperative to analyze their power consumption to provide quantitative results that help maximize battery life in IoT transportation systems. Although is well known that MQTT consumes less power than HTTP, a comparative analysis of their power consumption with long-time tests and different conditions has not yet been conducted. In this sense, a design and validation of an electronic cost-efficient platform system for remote real-time monitoring is proposed using a NodeMCU module, in which experimentation is carried out for HTTP and MQTT with different QoS levels to make a comparison and demonstrate the differences in power consumption. Furthermore, we characterize the behavior of the batteries in the systems and compare the theoretical analysis with real long-time test results. The experimentation using the MQTT protocol with QoS 0 and 1 was successful, resulting in power savings of 6.03% and 8.33%, respectively, compared with HTTP, demonstrating many more hours in the duration of the batteries, which could be very useful in technological solutions for the transport industry.

PTEN Loss Confers Resistance to Anti-PD-1 Therapy in Non-Small Cell Lung Cancer by Increasing Tumor Infiltration of Regulatory T Cells.

Immunotherapy resistance in non-small cell lung cancer (NSCLC) may be mediated by an immunosuppressive microenvironment, which can be shaped by the mutational landscape of the tumor. Here, we observed genetic alterations in the PTEN/PI3K/AKT/mTOR pathway and/or loss of PTEN expression in >25% of patients with NSCLC, with higher frequency in lung squamous carcinomas (LUSC). Patients with PTEN-low tumors had higher levels of PD-L1 and PD-L2 and showed worse progression-free survival when treated with immunotherapy. Development of a Pten-null LUSC mouse model revealed that tumors with PTEN loss were refractory to antiprogrammed cell death protein 1 (anti-PD-1), highly metastatic and fibrotic, and secreted TGFß/CXCL10 to promote conversion of CD4+ lymphocytes into regulatory T cells (Treg). Human and mouse PTEN-low tumors were enriched in Tregs and expressed higher levels of immunosuppressive genes. Importantly, treatment of mice bearing Pten-null tumors with TLR agonists and anti-TGFß antibody aimed to alter this immunosuppressive microenvironment and led to tumor rejection and immunologic memory in 100% of mice. These results demonstrate that lack of PTEN causes immunotherapy resistance in LUSCs by establishing an immunosuppressive tumor microenvironment that can be reversed therapeutically. SIGNIFICANCE: PTEN loss leads to the development of an immunosuppressive microenvironment in lung cancer that confers resistance to anti-PD-1 therapy, which can be overcome by targeting PTEN loss-mediated immunosuppression.

Cancer Cell-Intrinsic Alterations Associated with an Immunosuppressive Tumor Microenvironment and Resistance to Immunotherapy in Lung Cancer.

Despite the great clinical success of immunotherapy in lung cancer patients, only a small percentage of them (<40%) will benefit from this therapy alone or combined with other strategies. Cancer cell-intrinsic and cell-extrinsic mechanisms have been associated with a lack of response to immunotherapy. The present study is focused on cancer cell-intrinsic genetic, epigenetic, transcriptomic and metabolic alterations that reshape the tumor microenvironment (TME) and determine response or refractoriness to immune checkpoint inhibitors (ICIs). Mutations in KRAS, SKT11(LKB1), KEAP1 and TP53 and co-mutations of these genes are the main determinants of ICI response in non-small-cell lung cancer (NSCLC) patients. Recent insights into metabolic changes in cancer cells that impose restrictions on cytotoxic T cells and the efficacy of ICIs indicate that targeting such metabolic restrictions may favor therapeutic responses. Other emerging pathways for therapeutic interventions include epigenetic modulators and DNA damage repair (DDR) pathways, especially in small-cell lung cancer (SCLC). Therefore, the many potential pathways for enhancing the effect of ICIs suggest that, in a few years, we will have much more personalized medicine for lung cancer patients treated with immunotherapy. Such strategies could include vaccines and chimeric antigen receptor (CAR) cells.

Histoplasmosis e infección por SARS-CoV-2 en un paciente críticamente enfermo

Introducción: La histoplasmosis es causada por el hongo dimórfico Histoplasma capsulatum, cuyas manifestaciones clínicas varían desde un cuadro asintomático hasta una enfermedad diseminada y altamente mortal. Objetivo: Presentar el caso de un paciente con diagnóstico de histoplasmosis diseminada e infección por SARS-CoV-2. Caso clínico: Se presenta el caso de un hombre de 79 años con antecedentes de hipertensión arterial sistémica y diabetes mellitus tipo 2. Ingresa por tos no productiva de una semana de evolución, disnea y fatiga de medianos esfuerzos; refiere tener prueba de antígeno positivo para infección por SARS-CoV-2. Durante la hospitalización presenta un deterioro clínico, dado por necesidad de ventilación mecánica, por infección respiratoria asociada a la COVID-19. Además, presenta adenopatías, hepatoesplenomegalia y pápulas umbilicadas del color de la piel sugestivas de infección fúngica diseminada. Ante e la sospecha de coinfección, se confirma la infección por Histoplasma capsulatum por medio de minilavado broncoalveolar e inicia tratamiento antifúngico; sin embargo, el paciente presenta deterioro clínico persistente y fallece. Conclusión: Los casos de coinfecciones con la COVID-19 en pacientes sin enfermedades crónicas o estados de inmunosupresión son escasos, es un reto para el personal médico su diagnóstico y requiere tener en cuenta infecciones micóticas pulmonares como la criptococosis o la histoplasmosis en la insuficiencia respiratoria asociada a la infección por el SARS-CoV-2.

Introduction: Histoplasmosis is caused by the dimorphic fungus Histoplasma capsulatum, whose clinical manifestations range from asymptomatic to disseminated and highly fatal disease. Objective: To present the case of a patient diagnosed with disseminated histoplasmosis and SARS-CoV-2 infection. Clinical case: The case of a 79-year-old man is presented with a history of systemic arterial hypertension and type 2 diabetes mellitus. He was admitted for a week with nonproductive cough, dyspnea, and fatigue on moderate exertion, and reported having a positive antigen test for SARS- CoV-2. During hospitalization, he presented clinical deterioration, needing mechanical ventilation due to respiratory infection associated with COVID-19. Despite this, he presented lymphadenopathy, hepatosplenomegaly, and umbilicated skin-colored papules suggestive of disseminated fungal infection. Suspecting co-infection, infection by Histoplasma capsulatum was confirmed by means of mini-bronchoalveolar lavage and antifungal treatment was initiated; however, the patient presented persistent clinical deterioration and died. Conclusion: Cases of co-infections with COVID-19 in patients without chronic diseases or immunosuppressive states are rare, their diagnosis being a challenge for medical personnel and requiring consideration of pulmonary fungal infections such as cryptococcosis or histoplasmosis in associated respiratory failure. to SARS-CoV-2 infection.

Exploring multisensory integration of non-naturalistic sounds on body perception in young females with eating disorders symptomatology: a study protocol.

BACKGROUND: Bodily illusions can be used to investigate the experience of being in a body by manipulating the underlying processes of multisensory integration. Research suggests that people with eating disorders (EDs) may have impairments in visual, interoceptive, proprioceptive, and tactile bodily perception. Furthermore, people with EDs also show abnormalities in integrating multisensory visuo-tactile and visual-auditory signals related to the body, which may contribute to the development of body image disturbances. Visuo-auditory integration abnormalities have been observed also in people with subthreshold ED symptomatology. However, it remains unclear whether these impairments are specific to bodily signals or if they extend to any auditory signals. METHODS: We will recruit 50 participants (aged 18-24; females assigned at birth) with ED symptomatology (subthreshold group) and 50 control participants. The Eating Disorder Examination Questionnaire will be administered to screen for ED symptomatology and divide the sample into two groups accordingly (control and subthreshold group using a clinical cut-off score of 2.8). The strength of both illusions will be measured implicitly with estimations of body part position and size, and explicitly with self-report questionnaires. As a secondary aim, regression analysis will be run to test the predictive role of susceptibility for both illusions on interoceptive body awareness (measured by the Multidimensional Assessment of Interoceptive Awareness Scale) and sensory-processing sensitivity (measured by the Highly Sensitive Person Scale). DISCUSSION: Our study may contribute to our understanding of the mechanisms underlying body image disturbances. The results may pave the way for novel clinical interventions targeting early symptoms prior to the development of the disorder in young females.

This study aims to investigate whether individuals with subthreshold eating disorder (ED) symptoms show differences in the integration of proprioceptive and auditory cues in relation to body representation, as compared to healthy controls. This will be examined by focusing on two different body parts (finger and waist) with different levels of emotional significance for individuals with EDs. Participants will be screened for ED symptoms and divided into groups accordingly. The strength of the illusions will be measured using estimations of body part position and size, as well as self-report questionnaires. Regression analysis will be used to assess the predictive role of susceptibility to the body illusions on interoceptive body awareness and sensory-processing sensitivity. The results of this study may have implications for understanding the underlying mechanisms of body image disturbances in EDs, and inform the development of clinical interventions for individuals with subthreshold EDs.

Polymeric nanocapsules loaded with poly(I:C) and resiquimod to reprogram tumor-associated macrophages for the treatment of solid tumors.

Background: In the tumor microenvironment (TME), tumor-associated macrophages (TAMs) play a key immunosuppressive role that limits the ability of the immune system to fight cancer. Toll-like receptors (TLRs) ligands, such as poly(I:C) or resiquimod (R848) are able to reprogram TAMs towards M1-like antitumor effector cells. The objective of our work has been to develop and evaluate polymeric nanocapsules (NCs) loaded with poly(I:C)+R848, to improve drug stability and systemic toxicity, and evaluate their targeting and therapeutic activity towards TAMs in the TME of solid tumors. Methods: NCs were developed by the solvent displacement and layer-by-layer methodologies and characterized by dynamic light scattering and nanoparticle tracking analysis. Hyaluronic acid (HA) was chemically functionalized with mannose for the coating of the NCs to target TAMs. NCs loaded with TLR ligands were evaluated in vitro for toxicity and immunostimulatory activity by Alamar Blue, ELISA and flow cytometry, using primary human monocyte-derived macrophages. For in vivo experiments, the CMT167 lung cancer model and the MN/MCA1 fibrosarcoma model metastasizing to lungs were used; tumor-infiltrating leukocytes were evaluated by flow cytometry and multispectral immunophenotyping. Results: We have developed polymeric NCs loaded with poly(I:C)+R848. Among a series of 5 lead prototypes, protamine-NCs were selected based on their physicochemical properties (size, charge, stability) and in vitro characterization, showing good biocompatibility on primary macrophages and ability to stimulate their production of T-cell attracting chemokines (CXCL10, CCL5) and to induce M1-like macrophages cytotoxicity towards tumor cells. In mouse tumor models, the intratumoral injection of poly(I:C)+R848-protamine-NCs significantly prevented tumor growth and lung metastasis. In an orthotopic murine lung cancer model, the intravenous administration of poly(I:C)+R848-prot-NCs, coated with an additional layer of HA-mannose to improve TAM-targeting, resulted in good antitumoral efficacy with no apparent systemic toxicity. While no significant alterations were observed in T cell numbers (CD8, CD4 or Treg), TAM-reprogramming in treated mice was confirmed by the relative decrease of interstitial versus alveolar macrophages, having higher CD86 expression but lower CD206 and Arg1 expression in the same cells, in treated mice. Conclusion: Mannose-HA-protamine-NCs loaded with poly(I:C)+R848 successfully reprogram TAMs in vivo, and reduce tumor progression and metastasis spread in mouse tumors.

Intraoperative and postoperative impact of pretransplantation transjugular intrahepatic portosystemic shunts in orthotopic liver transplantations: A systematic review and meta-analysis.

Objectives: Orthotopic liver transplantation (OLT) remains the definitive treatment for patients afflicted with end-stage liver disease (ESLD). Transjugular intrahepatic portosystemic shunts (TIPS) have been adapted as a bridge to transplantation, allowing partial normalization of portal pressure and associated symptom improvement. Conflicting evidence exists on TIPS' impact on operative procedures. This study aimed to analyze available evidence on patients who underwent OLT with prior TIPS compared to OLT alone with the intent to determine TIPS' impact on surgical outcomes. Material and Methods: Following PRISMA guidelines, a systematic review was conducted, identifying studies comparing TIPS + OLT versus OLT alone in patients with ESLD. Data were analyzed using Review Manager 5.3. Results: Thirteen studies were included. Operative time, packed red blood cells transfusions, intensive care unit admission, length of stay, dialysis, serum creatinine levels, ascites, vascular complications, bleeding revisions, reintervention, and other complications rates were similar between both groups. Fresh frozen plasma transfusion -2.88 units (-5.42, -0.35; p= 0.03), was lower in the TIPS + OLT group. Conclusion: Our study found TIPS can be safely employed without having detrimental impacts on OLT outcomes, furthermore, these findings also suggest TIPS does not increase bleeding or complications.

RNA Captures More Cations than DNA: Insights from Molecular Dynamics Simulations.

The distribution of cations around nucleic acids is essential for a broad variety of processes ranging from DNA condensation and RNA folding to the detection of biomolecules in biosensors. Predicting the exact distribution of ions remains challenging since the distribution and, hence, a broad variety of nucleic acid properties depend on the salt concentration, the valency of the ions, and the ion type. Despite the importance, a general theory to quantify ion-specific effects for highly charged biomolecules is still lacking. Moreover, recent experiments reveal that despite their similar building blocks, DNA and RNA duplexes can react differently to the same ionic conditions. The aim of our current work is to provide a comprehensive set of molecular dynamics simulations using more than 180 µs of simulation time. For the mono- and divalent cations Li+, Na+, K+, Cs+, Ca2+, Sr2+, and Ba2+, the simulations allow us to reveal the ion-specific distributions and binding patterns for DNA and RNA duplexes. The microscopic insights from the simulations display the origin of ion-specificity and shed light on the question of why DNA and RNA show opposing behavior in the same ionic conditions. Finally, the detailed binding patterns from the simulations reveal why RNA can capture more cations than DNA.

A Passive Three Degree of Freedom Transtibial Prosthesis With Adjustable Coronal Compliance and Independent Toe Joint.

The effects of including lateral compliance or a toe joint in transtibial prostheses have been studied independently, showing the potential to improve the gait biomechanics in terms of stability, walking speed, and metabolic cost. However, both of these features are not commonly found in commercial prostheses despite their importance in human gait. In this work, we present a multi-axis passive transtibial prosthesis with three degrees of freedom (DOF). The prosthesis includes a compliant and adjustable coronal articulation using beam springs, an independent 3D-printed flexible forefoot as a toe joint, and sagittal dorsiflexion-plantarflexion stiffness using a helicoidal spring. We mechanically characterize each degree of freedom in terms of the provided stiffness. The measured stiffness values were 3.26Nm/deg, 4.94, or 5.63 Nm/deg in the sagittal plane (with different springs), and 2.54 Nm/deg, 2.79 Nm/deg, 2.94 Nm/deg, or 3.72 Nm/deg in the coronal plane (by adjusting the mechanism). Finally, the effect of different types of infill and infill levels for the 3D printed toes were explored, showing stiffness varying from 2.05 N/mm to 350 N/mm. The obtained sagittal stiffness is beneath the ones found in able-bodied persons; in contrast, the lateral stiffness values are comparatively higher than that of the able-bodied persons. However, the current design is simple to rearrange and modify the stiffness values. Lastly, the wide range of stiffness achievable in the 3D printed toes can be useful to achieve proper torque requirements in the forefoot for a broad range of users.

Investigating psychological variables for technologies promoting physical activity.

Background: Many technological interventions designed to promote physical activity (PA) have limited efficacy and appear to lack important factors that could increase engagement. This may be due to a discrepancy between research conducted in this space, and software designers' and developers' use of this research to inform new digital applications. Objectives: This study aimed to identify (1) what are the variables that act as barriers and facilitators to PA and (2) which PA variables are currently considered in the design of technologies promoting PA including psychological, physical, and personal/contextual ones which are critical in promoting PA. We emphasize psychological variables in this work because of their sparse and often simplistic integration in digital applications for PA. Methods: We conducted two systematized reviews on PA variables, using PsycInfo and Association for Computing Machinery Digital Libraries for objectives 1 and 2. Results: We identified 38 PA variables (mostly psychological ones) including barriers/facilitators in the literature. 17 of those variables were considered when developing digital applications for PA. Only few studies evaluate PA levels in relation to these variables. The same barriers are reported for all weight groups, though some barriers are stronger in people with obesity. Conclusions: We identify PA variables and illustrate the lack of consideration of these in the design of PA technologies. Digital applications to promote PA may have limited efficacy if they do not address variables acting as facilitators or barriers to participation in PA, and that are important to people representing a range of body weight characteristics.

Innate and Adaptive Responses of Intratumoral Immunotherapy with Endosomal Toll-Like Receptor Agonists.

Toll-like receptors (TLRs) are natural initial triggers of innate and adaptive immune responses. With the advent of cancer immunotherapy, nucleic acids engineered as ligands of endosomal TLRs have been investigated for the treatment of solid tumors. Despite promising results, their systemic administration, similarly to other immunotherapies, raises safety issues. To overcome these problems, recent studies have applied the direct injection of endosomal TLR agonists in the tumor and/or draining lymph nodes, achieving high local drug exposure and strong antitumor response. Importantly, intratumoral delivery of TLR agonists showed powerful effects not only against the injected tumors but also often against uninjected lesions (abscopal effects), resulting in some cases in cure and antitumoral immunological memory. Herein, we describe the structure and function of TLRs and their role in the tumor microenvironment. Then, we provide our vision on the potential of intratumor versus systemic delivery or vaccination approaches using TLR agonists, also considering the use of nanoparticles to improve their targeting properties. Finally, we collect the preclinical and clinical studies applying intratumoral injection of TLR agonists as monotherapies or in combination with: (a) other TLR or STING agonists; (b) other immunotherapies; (c) radiotherapy or chemotherapy; (d) targeted therapies.

The Effects of Brief Heat During Early Booting on Reproductive, Developmental, and Chlorophyll Physiological Performance in Common Wheat (Triticum aestivum L.).

Rising temperatures due to climate change threaten agricultural crop productivity. As a cool-season crop, wheat is heat-sensitive, but often exposed to high temperatures during the cultivation period. In the current study, a bread wheat panel of spring wheat genotypes, including putatively heat-tolerant Australian and CIMMYT genotypes, was exposed to a 5-day mild (34°C/28°C, day/night) or extreme (37°C/27°C) heat stress during the sensitive pollen developmental stage. Worsening effects on anther morphology were observed, as heat stress increased from mild to extreme. Even under mild heat, a significant decrease in pollen viability and number of grains per spike from primary spike was observed compared with the control (21°C/15°C), with Sunstar and two CIMMYT breeding lines performing well. A heat-specific positive correlation between the two traits indicates the important role of pollen fertility for grain setting. Interestingly, both mild and extreme heat induced development of new tillers after the heat stress, providing an alternative sink for accumulated photosynthates and significantly contributing to the final yield. Measurements of flag leaf maximum potential quantum efficiency of photosystem II (Fv/Fm) showed an initial inhibition after the heat treatment, followed by a full recovery within a few days. Despite this, model fitting using chlorophyll soil plant analysis development (SPAD) measurements showed an earlier onset or faster senescence rate under heat stress. The data presented here provide interesting entry points for further research into pollen fertility, tillering dynamics, and leaf senescence under heat. The identified heat-tolerant wheat genotypes can be used to dissect the underlying mechanisms and breed climate-resilient wheat.

Twisting DNA by salt.

The structure and properties of DNA depend on the environment, in particular the ion atmosphere. Here, we investigate how DNA twist -one of the central properties of DNA- changes with concentration and identity of the surrounding ions. To resolve how cations influence the twist, we combine single-molecule magnetic tweezer experiments and extensive all-atom molecular dynamics simulations. Two interconnected trends are observed for monovalent alkali and divalent alkaline earth cations. First, DNA twist increases monotonously with increasing concentration for all ions investigated. Second, for a given salt concentration, DNA twist strongly depends on cation identity. At 100 mM concentration, DNA twist increases as Na+ < K+ < Rb+ < Ba2+ < Li+ ≈ Cs+ < Sr2+ < Mg2+ < Ca2+. Our molecular dynamics simulations reveal that preferential binding of the cations to the DNA backbone or the nucleobases has opposing effects on DNA twist and provides the microscopic explanation of the observed ion specificity. However, the simulations also reveal shortcomings of existing force field parameters for Cs+ and Sr2+. The comprehensive view gained from our combined approach provides a foundation for understanding and predicting cation-induced structural changes both in nature and in DNA nanotechnology.

Eye movements and eating disorders: protocol for an exploratory experimental study examining the relationship in young-adult women with subclinical symptomatology.

BACKGROUND: Recent research indicates that patients with anorexia (AN) show specific eye movement abnormalities such as shorter prosaccade latencies, more saccade inhibition errors, and increased rate of saccadic intrusions compared to participants without AN. However, it remains unknown whether these abnormal eye movement patterns, which may serve as potential biomarkers and endophenotypes for an early diagnosis and preventive clinical treatments, start to manifest also in people with subclinical eating disorders (ED) symptomatology. Therefore, we propose a protocol for an exploratory experimental study to investigate whether participants with subclinical ED symptomatology and control participants differ in their performance on several eye movement tasks. METHODS: The sample will be recruited through convenience sampling. The Eating Disorder Examination Questionnaire will be administered as a screening tool to split the sample into participants with subclinical ED symptomatology and control participants. A fixation task, prosaccade/antisaccade task, and memory-guided task will be administered to both groups. Additionally, we will measure anxiety and premorbid intelligence as confounding variables. Means comparison, exploratory Pearson's correlations and discriminant analysis will be performed. DISCUSSION: This study will be the first to elucidate the presence of specific eye movement abnormalities in participants with subclinical ED symptomatology. The results may open opportunities for developing novel diagnostic tools/therapies being helpful to the EDs research community and allied fields.