Harnessing technology for infectious disease response in conflict zones: Challenges, innovations, and policy implications.

Epidemic outbreaks of infectious diseases in conflict zones are complex threats to public health and humanitarian activities that require creativity approaches of reducing their damage. This narrative review focuses on the technology intersection with infectious disease response in conflict zones, and complexity of healthcare infrastructure, population displacement, and security risks. This narrative review explores how conflict-related destruction is harmful towards healthcare systems and the impediments to disease surveillance and response activities. In this regards, the review also considered the contributions of technological innovations, such as the improvement of epidemiological surveillance, mobile health (mHealth) technologies, genomic sequencing, and surveillance technologies, in strengthening infectious disease management in conflict settings. Ethical issues related to data privacy, security and fairness are also covered. By advisement on policy that focuses on investment in surveillance systems, diagnostic capacity, capacity building, collaboration, and even ethical governance, stakeholders can leverage technology to enhance the response to infectious disease in conflict settings and, thus, protect the global health security. This review is full of information for researchers, policymakers, and practitioners who are dealing with the issues of infectious disease outbreaks in conflicts worn areas.

A Human-Scale Clinically Ready Electromagnetic Navigation System for Magnetically Responsive Biomaterials and Medical Devices.

Magnetic navigation systems are used to precisely manipulate magnetically responsive materials enabling the realization of new minimally invasive procedures using magnetic medical devices. Their widespread applicability has been constrained by high infrastructure demands and costs. The study reports on a portable electromagnetic navigation system, the Navion, which is capable of generating a large magnetic field over a large workspace. The system is easy to install in hospital operating rooms and transportable through health care facilities, aiding in the widespread adoption of magnetically responsive medical devices. First, the design and implementation approach for the system are introduced and its performance is characterized. Next, in vitro navigation of different microrobot structures is demonstrated using magnetic field gradients and rotating magnetic fields. Spherical permanent magnets, electroplated cylindrical microrobots, microparticle swarms, and magnetic composite bacteria-inspired helical structures are investigated. The navigation of magnetic catheters is also demonstrated in two challenging endovascular tasks: 1) an angiography procedure and 2) deep navigation within the circle of Willis. Catheter navigation is demonstrated in a porcine model in vivo to perform an angiography under magnetic guidance.

Utilization of a Meningitis/Encephalitis PCR panel at the University Hospital Basel - a retrospective study to develop a diagnostic decision rule.

Background: The Biofire® FilmArray® Meningitis/Encephalitis (ME) PCR panel covers 14 viral, bacterial, and fungal pathogens and has been implemented in many institutions worldwide. Post-marketing studies indicate a reduced sensitivity and overutilization underscoring the need for a more targeted usage. The aim of our study is to describe the utilization of the ME panel and to develop a diagnostic-stewardship based decision rule. Materials: Adult patients, who underwent CSF analysis with the ME panel between August 2016 and June 2021 at the University Hospital Basel, were included. Demographic, clinical, microbiological, and laboratory data were extracted from the electronic health record. Factors associated with a positive ME panel result were identified, and a decision rule was developed to potentially optimize the diagnostic yield and reduce the number of unnecessary tests. Results: 1,236 adult patients received at least one panel in the observed period, of whom 106 panels tested positive (8.6%). The most frequently observed pathogens were Varicella Zoster Virus (VZV, 27%), Streptococcus pneumoniae (19%), Enterovirus (16%), Herpes simplex Virus 1/2 (16%), and Human Herpesvirus 6 (HHV-6, 13%). Fever, vomiting, headache, and photophobia were more frequently present in test positive patients as were significantly higher CSF leukocytes and protein concentrations. When simulating a decision rule based on CSF leukocytes and protein concentration, only 35% of all patients would have qualified for a ME panel tests, thereby increasing the positivity rate to 22.7%. 10 of 106 positive ME panels would have been missed, only involving HHV-6 and VZV (6 and 4 cases, respectively). As these subjects were either severely immunocompromised or had clinical features of shingles we propose extending the testing algorithm by including those criteria. Conclusion: The ME panel positivity rate at our institution was similar as previously published. Our results highlight the need for diagnostic-stewardship interventions when utilizing this assay by implementing a stepwise approach based on a limited number of clinical and laboratory features. This decision rule may improve the pretest probability of a positive test result, increase the quality of test utilization, and reduce costs.

Recovery of left ventricular systolic function in peripartum cardiomyopathy: an observational study from rural Tanzania.

BACKGROUND: The aim of this study was to evaluate the recovery rate of the left ventricular systolic function of women diagnosed with peripartum cardiomyopathy receiving specialized care in rural Tanzania. METHODS: In this observational study, women diagnosed with peripartum cardiomyopathy at a referral center in rural Tanzania between December 2015 and September 2021 were included. Women diagnosed between February and September 2021 were followed prospectively, those diagnosed between December 2015 and January 2021 were tracked back for a follow-up echocardiography. All participants received a clinical examination, a comprehensive echocardiogram, and a prescription of guideline-directed medical therapy. The primary outcome was recovery of the left ventricular systolic function (left ventricular ejection fraction > 50%). RESULTS: Median age of the 110 participants was 28.5 years (range 17-45). At enrolment, 49 (45%) participants were already on cardiac medication, 50 (45%) had severe eccentric hypertrophy of the left ventricle, and the median left ventricular ejection fraction was 30% (range 15-46). After a median follow-up of 8.98 months (IQR 5.72-29.37), 61 (55%) participants were still on cardiac medication. Full recovery of the left ventricular systolic function was diagnosed in 76 (69%, 95% CI 59.6-77.6%) participants. In the multivariate analysis, a higher left ventricular ejection fraction at baseline was positively associated with full recovery (each 5% increase; OR 1.7, 95% CI 1.10-2.62, p = 0.012), while higher age was inversely associated (each 10 years increase; OR 0.40, 95% CI 0.19-0.82, p = 0.012). CONCLUSION: Left ventricular systolic function recovered completely in 69% of study participants with peripartum cardiomyopathy from rural Tanzania under specialized care.

A Naturally Inspired Extrusion-Based Microfluidic Approach for Manufacturing Tailorable Magnetic Soft Continuum Microrobotic Devices.

Soft materials play a crucial role in small-scale robotic applications by closely mimicking the complex motion and morphing behavior of organisms. However, conventional fabrication methods face challenges in creating highly integrated small-scale soft devices. In this study, microfluidics is leveraged to precisely control reaction-diffusion (RD) processes to generate multifunctional and compartmentalized calcium-cross-linkable alginate-based microfibers. Under RD conditions, sophisticated alginate-based fibers are produced for magnetic soft continuum robotics applications with customizable features, such as geometry (compact or hollow), degree of cross-linking, and the precise localization of magnetic nanoparticles (inside the core, surrounding the fiber, or on one side). This fine control allows for tuning the stiffness and magnetic responsiveness of the microfibers. Additionally, chemically cleavable regions within the fibers enable disassembly into smaller robotic units or roll-up structures under a rotating magnetic field. These findings demonstrate the versatility of microfluidics in processing highly integrated small-scale devices.

The Andes as a semi-permeable geographical barrier: Genetic connectivity between structured populations in a widespread spider.

Geographical barriers like mountain ranges impede genetic exchange among populations, promoting diversification. The effectiveness of these barriers in limiting gene flow varies between lineages due to each species' dispersal modes and capacities. Our understanding of how the Andes orogeny contributes to species diversification comes from well-studied vertebrates and a few arthropods and plants, neglecting organisms unable to fly or walk long distances. Some arachnids, such as Gasteracantha cancriformis, have been hypothesized to disperse long distances via ballooning (i.e. using their silk to interact with the wind). Yet, we do not know how the environment and geography shape its genetic diversity. Therefore, we tested whether the Andes contributed to the diversification of G. cancriformis acting as an absolute or semi-permeable barrier to genetic connectivity between populations of this spider at opposite sides of the mountain range. We sampled thousands of loci across the distribution of the species and implemented population genetics, phylogenetic, and landscape genetic analyses. We identified two genetically distinct groups structured by the Central Andes, and a third less structured group in the Northern Andes that shares ancestry with the previous two. This structure is largely explained by the altitude along the Andes, which decreases in some regions, possibly facilitating cross-Andean dispersal and gene flow. Our findings support that altitude in the Andes plays a major role in structuring populations in South America, but the strength of this barrier can be overcome by organisms with long-distance dispersal modes together with altitudinal depressions.

Las barreras geográficas como las cordilleras montañosas impiden el intercambio genético entre poblaciones, promoviendo la diversificación. La efectividad de estas barreras para limitar el flujo genético varía entre linajes debido a los modos y capacidades de dispersión de cada especie. Nuestra comprensión de cómo la orogenia de los Andes contribuye a la diversificación de especies proviene de vertebrados y algunos artrópodos y plantas bien estudiados, descuidando a los organismos incapaces de volar o caminar grandes distancias. Se ha hipotetizado que algunas arañas, como Gasteracantha cancriformis, se dispersan a grandes distancias mediante la técnica de "ballooning" (es decir, utilizando su seda para interactuar con el viento). Sin embargo, no sabemos cómo el entorno y la geografía han dado forma a su diversidad genética. Por lo tanto, probamos si los Andes contribuyeron a la diversificación de G. cancriformis actuando como una barrera absoluta o permeable para la conectividad genética entre poblaciones de esta araña en lados opuestos de la cordillera. Muestreamos miles de loci a través de la distribución de la especie e implementamos análisis de genética de poblaciones, filogenéticos y de genética del paisaje. Identificamos dos grupos genéticamente distintos estructurados por los Andes Centrales, y un tercer grupo menos estructurado en los Andes del Norte que comparte ascendencia con los dos anteriores. Esta estructura se explica en gran medida por la altitud a lo largo de los Andes, que disminuye en algunas regiones, posiblemente facilitando la dispersión y el flujo genético a través de los Andes. Nuestros hallazgos apoyan que la altitud en los Andes juega un papel importante en la estructuración de las poblaciones en América del Sur, pero la fuerza de esta barrera puede ser superada por organismos con modos de dispersión a larga distancia junto con depresiones altitudinales.

Mathematical Model-Driven Deep Learning Enables Personalized Adaptive Therapy.

Standard-of-care treatment regimens have long been designed for maximal cell killing, yet these strategies often fail when applied to metastatic cancers due to the emergence of drug resistance. Adaptive treatment strategies have been developed as an alternative approach, dynamically adjusting treatment to suppress the growth of treatment-resistant populations and thereby delay, or even prevent, tumor progression. Promising clinical results in prostate cancer indicate the potential to optimize adaptive treatment protocols. Here, we applied deep reinforcement learning (DRL) to guide adaptive drug scheduling and demonstrated that these treatment schedules can outperform the current adaptive protocols in a mathematical model calibrated to prostate cancer dynamics, more than doubling the time to progression. The DRL strategies were robust to patient variability, including both tumor dynamics and clinical monitoring schedules. The DRL framework could produce interpretable, adaptive strategies based on a single tumor burden threshold, replicating and informing optimal treatment strategies. The DRL framework had no knowledge of the underlying mathematical tumor model, demonstrating the capability of DRL to help develop treatment strategies in novel or complex settings. Finally, a proposed five-step pathway, which combined mechanistic modeling with the DRL framework and integrated conventional tools to improve interpretability compared with traditional "black-box" DRL models, could allow translation of this approach to the clinic. Overall, the proposed framework generated personalized treatment schedules that consistently outperformed clinical standard-of-care protocols. SIGNIFICANCE: Generation of interpretable and personalized adaptive treatment schedules using a deep reinforcement framework that interacts with a virtual patient model overcomes the limitations of standardized strategies caused by heterogeneous treatment responses.

Case report: C1/2 rotational instability progressing to extreme subaxial hyperkyphosis in an adolescent with severe catatonia.

Introduction: Autism spectrum disorder (ASD) is characterized by deficits in social communication, repetitive behaviors, and can be accompanied by a spectrum of psychiatric symptoms, such as schizophrenia and catatonia. Rarely, these symptoms, if left untreated, can result in spinal deformities. Research question and case description: This case report details the treatment of a 16-year-old male ASD patient with catatonic schizophrenia and mutism, presenting with neck pain, left-rotated torticollis, and fever. MRI revealed atlantoaxial rotational instability and spinal cord compression from a dislocated dens axis. After inconclusive biopsies, empirical antibiotics, hard collar and halo fixation treatment, persistent instability necessitated C1/2 fusion. The ongoing catatonia was addressed with electroconvulsive therapy. Concurrently, he developed severe subaxial hyperkyphosis. The report examines the decision-making between conservative and surgical management for an adolescent with significant psychiatric comorbidity and progressive spinal symptoms against a backdrop of uncertain etiology. Materials and methods: A case report and review of the literature. Results: Posterior C1-C7 stabilization was successfully executed, effectively restoring cervical sagittal alignment, which was maintained throughout a two-year follow-up. Concurrently, the catatonia resolved. Discussion and conclusion: To our knowledge, this is the third reported case of severe cervical deformity associated with fixed posture in a psychiatric patient. This case report emphasizes the critical importance of multidisciplinary collaboration in managing the interplay between neuropsychiatric disorders and severe spinal deformities. It showcases the practicality and efficacy of surgical intervention for persistent cervical deformity in pediatric schizophrenia patients, highlighting the necessity for a comprehensive risk-benefit analysis.

Structural Analysis of Breast-Milk αS1-Casein: An α-Helical Conformation Is Required for TLR4-Stimulation.

Breast-milk αS1-casein is a Toll-like receptor 4 (TLR4) agonist, whereas phosphorylated αS1-casein does not bind TLR4. The objective of this study was to analyse the structural requirements for these effects. In silico analysis of αS1-casein indicated high α-helical content with coiled-coil characteristics. This was confirmed by CD-spectroscopy, showing the α-helical conformation to be stable between pH 2 and 7.4. After in vitro phosphorylation, the α-helical content was significantly reduced, similar to what it was after incubation at 80 °C. This conformation showed no in vitro induction of IL-8 secretion via TLR4. A synthetic peptide corresponding to V77-E92 of αS1-casein induced an IL-8 secretion of 0.95 ng/mL via TLR4. Our results indicate that αS1-casein appears in two distinct conformations, an α-helical TLR4-agonistic and a less α-helical TLR4 non-agonistic conformation induced by phosphorylation. This is to indicate that the immunomodulatory role of αS1-casein, as described before, could be regulated by conformational changes induced by phosphorylation.

A scalable synthesis of adjuvanting antigen depots based on metal-organic frameworks.

Vaccines have saved countless lives by preventing and even irradicating infectious diseases. Commonly used subunit vaccines comprising one or multiple recombinant proteins isolated from a pathogen demonstrate a better safety profile than live or attenuated vaccines. However, the immunogenicity of these vaccines is weak, and therefore, subunit vaccines require a series of doses to achieve sufficient immunity against the pathogen. Here, we show that the biomimetic mineralization of the inert model antigen, ovalbumin (OVA), in zeolitic imidazolate framework-8 (ZIF-8) significantly improves the humoral immune response over three bolus doses of OVA (OVA 3×). Encapsulation of OVA in ZIF-8 (OVA@ZIF) demonstrated higher serum antibody titers against OVA than OVA 3×. OVA@ZIF vaccinated mice displayed higher populations of germinal center (GC) B cells and IgG1+ GC B cells as opposed to OVA 3×, indicative of class-switching recombination. We show that the mechanism of this phenomenon is at least partly owed to the metalloimmunological effects of the zinc metal as well as the sustained release of OVA from the ZIF-8 composite. The system acts as an antigen reservoir for antigen-presenting cells to traffic into the draining lymph node, enhancing the humoral response. Lastly, our model system OVA@ZIF is produced quickly at the gram scale in a laboratory setting, sufficient for up to 20 000 vaccine doses.

Impact of sex and gender on post-COVID-19 syndrome, Switzerland, 2020.

BackgroundWomen are overrepresented among individuals with post-acute sequelae of SARS-CoV-2 infection (PASC). Biological (sex) as well as sociocultural (gender) differences between women and men might account for this imbalance, yet their impact on PASC is unknown.AimWe assessed the impact of sex and gender on PASC in a Swiss population.MethodOur multicentre prospective cohort study included 2,856 (46% women, mean age 44.2 ± 16.8 years) outpatients and hospitalised patients with PCR-confirmed SARS-CoV-2 infection.ResultsAmong those who remained outpatients during their first infection, women reported persisting symptoms more often than men (40.5% vs 25.5% of men; p < 0.001). This sex difference was absent in hospitalised patients. In a crude analysis, both female biological sex (RR = 1.59; 95% CI: 1.41-1.79; p < 0.001) and a score summarising gendered sociocultural variables (RR = 1.05; 95% CI: 1.03-1.07; p < 0.001) were significantly associated with PASC. Following multivariable adjustment, biological female sex (RR = 0.96; 95% CI: 0.74-1.25; p = 0.763) was outperformed by feminine gender-related factors such as a higher stress level (RR = 1.04; 95% CI: 1.01-1.06; p = 0.003), lower education (RR = 1.16; 95% CI: 1.03-1.30; p = 0.011), being female and living alone (RR = 1.91; 95% CI: 1.29-2.83; p = 0.001) or being male and earning the highest income in the household (RR = 0.76; 95% CI: 0.60-0.97; p = 0.030).ConclusionSpecific sociocultural parameters that differ in prevalence between women and men, or imply a unique risk for women, are predictors of PASC and may explain, at least in part, the higher incidence of PASC in women. Once patients are hospitalised during acute infection, sex differences in PASC are no longer evident.

Occurrence of Major Perfluorinated Alkylate Substances in Human Blood and Target Organs.

Human exposure to perfluorinated alkylate substances (PFASs) is usually assessed from the concentrations in serum or plasma, assuming one-compartment toxicokinetics. To characterize body distributions of major PFASs, we obtained and extracted tissue samples from 19 forensic autopsies of healthy adult subjects who had died suddenly and were not known to have elevated levels of PFAS exposure. As target organs of toxicological importance, we selected the liver, kidneys, lungs, spleen, and brain, as well as whole blood. Samples weighing about 0.1 g were analyzed by liquid chromatography coupled to triple mass spectrometers. Minor variations in PFAS concentrations were found between the kidney cortex and medulla and between lung lobes. Organ concentrations of perfluorooctanoic sulfonate (PFOS) and perfluorononanoate (PFNA) correlated well with blood concentrations, while perfluorooctanoate (PFOA) and perfluorohexanoic sulfonate (PFHxS) showed more variable associations. Likewise, the liver concentrations correlated well with those of other organs. Calculations of relative distributions were carried out to assess the interdependence of organ retentions. Equilibrium model predictions largely explained the observed PFAS distributions, except for the brain. Although the samples were small and affected by a possible lack of homogeneity, these findings support the use of blood-PFAS concentrations as a measure of PFAS exposure, with the liver possibly acting as the main organ of retention.

On-Command Disassembly of Microrobotic Superstructures for Transport and Delivery of Magnetic Micromachines.

Magnetic microrobots have been developed for navigating microscale environments by means of remote magnetic fields. However, limited propulsion speeds at small scales remain an issue in the maneuverability of these devices as magnetic force and torque are proportional to their magnetic volume. Here, a microrobotic superstructure is proposed, which, as analogous to a supramolecular system, consists of two or more microrobotic units that are interconnected and organized through a physical (transient) component (a polymeric frame or a thread). The superstructures consist of microfabricated magnetic helical micromachines interlocked by a magnetic gelatin nanocomposite containing iron oxide nanoparticles (IONPs). While the microhelices enable the motion of the superstructure, the IONPs serve as heating transducers for dissolving the gelatin chassis via magnetic hyperthermia. In a practical demonstration, the superstructure's motion with a gradient magnetic field in a large channel, the disassembly of the superstructure and release of the helical micromachines by a high-frequency alternating magnetic field, and the corkscrew locomotion of the released helices through a small channel via a rotating magnetic field, is showcased. This adaptable microrobotic superstructure reacts to different magnetic inputs, which can be used to perform complex delivery procedures within intricate regions of the human body.

In Silico and In Vitro Search for Dual Inhibitors of the Trypanosoma brucei and Leishmania major Pteridine Reductase 1 and Dihydrofolate Reductase.

The parasites Trypanosoma brucei (Tb) and Leishmania major (Lm) cause the tropical diseases sleeping sickness, nagana, and cutaneous leishmaniasis. Every year, millions of humans, as well as animals, living in tropical to subtropical climates fall victim to these illnesses' health threats. The parasites' frequent drug resistance and widely spread natural reservoirs heavily impede disease prevention and treatment. Due to pteridine auxotrophy, trypanosomatid parasites have developed a peculiar enzyme system consisting of dihydrofolate reductase-thymidylate synthase (DHFR-TS) and pteridine reductase 1 (PTR1) to support cell survival. Extending our previous studies, we conducted a comparative study of the T. brucei (TbDHFR, TbPTR1) and L. major (LmDHFR, LmPTR1) enzymes to identify lead structures with a dual inhibitory effect. A pharmacophore-based in silico screening of three natural product databases (approximately 4880 compounds) was performed to preselect possible inhibitors. Building on the in silico results, the inhibitory potential of promising compounds was verified in vitro against the recombinant DHFR and PTR1 of both parasites using spectrophotometric enzyme assays. Twelve compounds were identified as dual inhibitors against the Tb enzymes (0.2 µM < IC50 < 85.1 µM) and ten against the respective Lm enzymes (0.6 µM < IC50 < 84.5 µM). These highly promising results may represent the starting point for the future development of new leads and drugs utilizing the trypanosomatid pteridine metabolism as a target.

Improved computational epitope profiling using structural models identifies a broader diversity of antibodies that bind to the same epitope.

The function of an antibody is intrinsically linked to the epitope it engages. Clonal clustering methods, based on sequence identity, are commonly used to group antibodies that will bind to the same epitope. However, such methods neglect the fact that antibodies with highly diverse sequences can exhibit similar binding site geometries and engage common epitopes. In a previous study, we described SPACE1, a method that structurally clustered antibodies in order to predict their epitopes. This methodology was limited by the inaccuracies and incomplete coverage of template-based modeling. In addition, it was only benchmarked at the level of domain-consistency on one virus class. Here, we present SPACE2, which uses the latest machine learning-based structure prediction technology combined with a novel clustering protocol, and benchmark it on binding data that have epitope-level resolution. On six diverse sets of antigen-specific antibodies, we demonstrate that SPACE2 accurately clusters antibodies that engage common epitopes and achieves far higher dataset coverage than clonal clustering and SPACE1. Furthermore, we show that the functionally consistent structural clusters identified by SPACE2 are even more diverse in sequence, genetic lineage, and species origin than those found by SPACE1. These results reiterate that structural data improve our ability to identify antibodies that bind to the same epitope, adding information to sequence-based methods, especially in datasets of antibodies from diverse sources. SPACE2 is openly available on GitHub (https://github.com/oxpig/SPACE2).

Paired Liver:Plasma PFAS Concentration Ratios from Adolescents in the Teen-LABS Study and Derivation of Empirical and Mass Balance Models to Predict and Explain Liver PFAS Accumulation.

Animal studies have pointed at the liver as a hotspot for per- and polyfluoroalkyl substances (PFAS) accumulation and toxicity; however, these findings have not been replicated in human populations. We measured concentrations of seven PFAS in matched liver and plasma samples collected at the time of bariatric surgery from 64 adolescents in the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study. Liver:plasma concentration ratios were perfectly explained (r2 > 0.99) in a multilinear regression (MLR) model based on toxicokinetic (TK) descriptors consisting of binding to tissue constituents and membrane permeabilities. Of the seven matched plasma and liver PFAS concentrations compared in this study, the liver:plasma concentration ratio of perfluoroheptanoic acid (PFHpA) was considerably higher than the liver:plasma concentration ratio of other PFAS congeners. Comparing the MLR model with an equilibrium mass balance model (MBM) suggested that complex kinetic transport processes are driving the unexpectedly high liver:plasma concentration ratio of PFHpA. Intratissue MBM modeling pointed to membrane lipids as the tissue constituents that drive the liver accumulation of long-chain, hydrophobic PFAS, whereas albumin binding of hydrophobic PFAS dominated PFAS distribution in plasma. The liver:plasma concentration data set, empirical MLR model, and mechanistic MBM modeling allow the prediction of liver from plasma concentrations measured in human cohort studies. Our study demonstrates that combining biomonitoring data with mechanistic modeling can identify underlying mechanisms of internal distribution and specific target organ toxicity of PFAS in humans.

Interaction of Substrates with γ-Secretase at the Level of Individual Transmembrane Helices-A Methodological Approach.

Intramembrane proteases, such as γ secretase, typically recruit multiple substrates from an excess of single-span membrane proteins. It is currently unclear to which extent substrate recognition depends on specific interactions of their transmembrane domains (TMDs) with TMDs of a protease. Here, we investigated a large number of potential pairwise interactions between TMDs of γ secretase and a diverse set of its substrates using two different configurations of BLaTM, a genetic reporter system. Our results reveal significant interactions between TMD2 of presenilin, the enzymatic subunit of γ secretase, and the TMD of the amyloid precursor protein, as well as of several other substrates. Presenilin TMD2 is a prime candidate for substrate recruitment, as has been shown from previous studies. In addition, the amyloid precursor protein TMD enters interactions with presenilin TMD 4 as well as with the TMD of nicastrin. Interestingly, the Gly-rich interfaces between the amyloid precursor protein TMD and presenilin TMDs 2 and 4 are highly similar to its homodimerization interface. In terms of methodology, the economics of the newly developed library-based method could prove to be a useful feature in related future work for identifying heterotypic TMD-TMD interactions within other biological contexts.

The heat is on: Investigating the effect of psychological pressure on competitive performance in elite surfing.

Competitive sport often creates a high-stake and thus a high-pressure environment for its athletes. In the past, research has pointed to the negative effect that competitive pressure might have on skills and movement executions that have been perfected through prior practice. The Attentional Control Theory: Sport (ACTS) suggests that specifically high situational pressure and prior performance failures may negatively affect an athlete's subsequent performance. This study aimed to investigate the influence of situational pressure and previous performance errors on performance (i.e., wave score) in elite surfing while considering various contextual factors. A total of 6497 actions, performed by 80 elite surfers (female n = 28; male n = 52), were annotated based on video recordings of the 2019 World Championship Tour (WCT). A multi-level model was used to analyse the effect of pressure, previous errors and other contextual factors on the wave scores of individual surfers (i.e., events were nested within athletes). Partially confirming previous research, prior errors caused a significant decrease in surfing performance on the following ride. However, neither a significant effect of situational pressure on performance nor inter-individual differences in how prior-errors and situational pressure affected performance were found.

Fe- and B-Chains in the Ti5-xFe1-yOs6+x+yB6 Structure Type Derived from Chemical Twinning of the Nb1-xOs1+xB Type: Experimental and Computational Investigations.

The complex metal-rich boride Ti5-xFe1-yOs6+x+yB6 (0 < x,y < 1), crystallizing in a new structure type (space group Cmcm, no. 63), was prepared by arc-melting. The new structure contains both isolated boron atoms and zigzag boron chains (B-B distance of 1.74 Å), a rare combination among metal-rich borides. In addition, the structure also contains Fe-chains running parallel to the B-chains. Unlike in previously reported structures, these Fe-chains are offset from each other and arranged in a triangular manner with intrachain and interchain distances of 2.98 and 6.69 Å, respectively. Density functional theory (DFT) calculations predict preferred ferromagnetic interactions within each chain but only small energy differences for different magnetic interactions between them, suggesting a potentially weak long-range order. This new structure offers the opportunity to study new configurations and interactions of magnetic elements for the design of magnetic materials.

Self-assembly of a fluorescent virus-like particle for imaging in tissues with high autofluorescence.

Virus-like particles (VLPs) are engineered nanoparticles that mimic the properties of viruses-like high tolerance to heat and proteases-but lack a viral genome, making them non-infectious. They are easily modified chemically and genetically, making them useful in drug delivery, enhancing vaccine efficacy, gene delivery, and cancer immunotherapy. One such VLP is Qß, which has an affinity towards an RNA hairpin structure found in its viral RNA that drives the self-assembly of the capsid. It is possible to usurp the native way infectious Qß self-assembles to encapsidate its RNA to place enzymes inside the VLP's lumen as a protease-resistant cage. Further, using RNA templates that mimic the natural self-assembly of the native capsid, fluorescent proteins (FPs) have been placed inside VLPs in a "one pot" expression system. Autofluorescence in tissues can lead to misinterpretation of results and unreliable science, so we created a single-pot expression system that uses the fluorescent protein smURFP, which avoids autofluorescence and has spectral properties compatible with standard commercial filter sets on confocal microscopes. In this work, we were able to simplify the existing "one-pot" expression system while creating high-yielding fluorescent VLP nanoparticles that could easily be imaged inside lung epithelial tissue.