julilili42/papers huggingface dataset:
The Damietta Server: a comprehensive protein design toolkit
2024-04-25

Abstract The growing importance of protein design to various research disciplines motivates the development of integrative computational platforms that enhance the accessibility and interoperability of different design tools. To this end, we describe a web-based toolkit that builds on the Damietta protein design engine, which deploys a tensorized energy calculation framework. The Damietta Server seamlessly integrates different design tools, in addition to other tools such as message-passing neural networks and molecular dynamics routines, allowing the user to perform multiple operations on structural models and forward them across tools. The toolkit can be used for tasks such as core or interface design, symmetric design, mutagenic scanning, or conformational sampling, through an intuitive user interface. With the envisioned integration of more tools, the Damietta Server will provide a central resource for protein design and analysis, benefiting basic and applied biomedical research communities. The toolkit is available with no login requirement through https://damietta.de/.
α‐Synuclein seed amplification assay detects Lewy body co‐pathology in autosomal dominant Alzheimer's disease late in the disease course and dependent on Lewy pathology burden
2024-04-26

Abstract INTRODUCTION Amyloid beta and tau pathology are the hallmarks of sporadic Alzheimer's disease (AD) and autosomal dominant AD (ADAD). However, Lewy body pathology (LBP) is found in ≈ 50% of AD and ADAD brains. METHODS Using an α‐synuclein seed amplification assay (SAA) in cerebrospinal fluid (CSF) from asymptomatic ( n = 26) and symptomatic ( n = 27) ADAD mutation carriers, including 12 with known neuropathology, we investigated the timing of occurrence and prevalence of SAA positive reactivity in ADAD in vivo. RESULTS No asymptomatic participant and only 11% (3/27) of the symptomatic patients tested SAA positive. Neuropathology revealed LBP in 10/12 cases, primarily affecting the amygdala or the olfactory areas. In the latter group, only the individual with diffuse LBP reaching the neocortex showed α‐synuclein seeding activity in CSF in vivo. DISCUSSION Results suggest that in ADAD LBP occurs later than AD pathology and often as amygdala‐ or olfactory‐predominant LBP, for which CSF α‐synuclein SAA has low sensitivity. Highlights Cerebrospinal fluid (CSF) real‐time quaking‐induced conversion (RT‐QuIC) detects misfolded α‐synuclein in ≈ 10% of symptomatic autosomal dominant Alzheimer's disease (ADAD) patients. CSF RT‐QuIC does not detect α‐synuclein seeding activity in asymptomatic mutation carriers. Lewy body pathology (LBP) in ADAD mainly occurs as olfactory only or amygdala‐predominant variants. LBP develops late in the disease course in ADAD. CSF α‐synuclein RT‐QuIC has low sensitivity for focal, low‐burden LBP.
Facile Energy Release from Substituted Dewar Isomers of 1,2‐Dihydro‐1,2‐Azaborinines Catalyzed by Coinage Metal Lewis Acids
2024-04-26

Abstract Molecular solar thermal systems (MOST) represent an auspicious solution for the storage of solar energy. We report silver salts as a unique class of catalysts, capable of releasing the stored energy from the promising 1,2‐dihydro‐1,2‐azaborinine based MOST system. Mechanistic investigations provided insights into the silver catalyzed thermal backreaction, concurrently unveiling the first crystal structure of a 2‐aza‐3‐borabicyclo[2.2.0]hex‐5‐ene, the Dewar isomer of 1,2‐dihydro‐1,2‐azaborinine. Quantification of activation energies by kinetic experiments has elucidated the advantageous energy change associated with Lewis acid catalysts, a phenomenon corroborated through computational analysis. By means of low temperature NMR spectroscopy, mechanistic insights into the coordination of Ag + to the 1,2‐dihydro‐1,2‐azaborinine were gained.
Digital Health Interventions and Patient Safety in Abdominal Surgery
2024-04-26

Importance Over the past 2 decades, several digital technology applications have been used to improve clinical outcomes after abdominal surgery. The extent to which these telemedicine interventions are associated with improved patient safety outcomes has not been assessed in systematic and meta-analytic reviews. Objective To estimate the implications of telemedicine interventions for complication and readmission rates in a population of patients with abdominal surgery. Data Sources PubMed, Cochrane Library, and Web of Science databases were queried to identify relevant randomized clinical trials (RCTs) and nonrandomized studies published from inception through February 2023 that compared perioperative telemedicine interventions with conventional care and reported at least 1 patient safety outcome. Study Selection Two reviewers independently screened the titles and abstracts to exclude irrelevant studies as well as assessed the full-text articles for eligibility. After exclusions, 11 RCTs and 8 cohort studies were included in the systematic review and meta-analysis and 7 were included in the narrative review. Data Extraction and Synthesis Data were extracted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline and assessed for risk of bias by 2 reviewers. Meta-analytic estimates were obtained in random-effects models. Main Outcomes and Measures Number of complications, emergency department (ED) visits, and readmissions. Results A total of 19 studies (11 RCTs and 8 cohort studies) with 10 536 patients were included. The pooled risk ratio (RR) estimates associated with ED visits (RR, 0.78; 95% CI, 0.65-0.94) and readmissions (RR, 0.67; 95% CI, 0.58-0.78) favored the telemedicine group. There was no significant difference in the risk of complications between patients in the telemedicine and conventional care groups (RR, 1.05; 95% CI, 0.77-1.43). Conclusions and Relevance Findings of this systematic review and meta-analysis suggest that perioperative telehealth interventions are associated with reduced risk of readmissions and ED visits after abdominal surgery. However, the mechanisms of action for specific types of abdominal surgery are still largely unknown and warrant further research.
Xpert-Ultra Assay in Stool and Urine Samples to Improve Tuberculosis Diagnosis in Children: The Médecins Sans Frontières Experience in Guinea-Bissau and South Sudan
2024-04-26

Abstract Background More than half of childhood tuberculosis cases remain undiagnosed yearly. The World Health Organization recommends the Xpert-Ultra assay as a first pediatric diagnosis test, but microbiological confirmation remains low. We aimed to determine the diagnostic performance of Xpert-Ultra with stool and urine samples in presumptive pediatric tuberculosis cases in 2 high-tuberculosis-burden settings. Methods This Médecins Sans Frontières cross-sectional multicentric study took place at Simão Mendes Hospital, Guinea-Bissau (July 2019 to April 2020) and in Malakal Hospital, South Sudan (April 2021 to June 2023). Children aged 6 months to 15 years with presumptive tuberculosis underwent clinical and laboratory assessment, with 1 respiratory and/or extrapulmonary sample (reference standard [RS]), 1 stool, and 1 urine specimen analyzed with Xpert-Ultra. Results A total of 563 children were enrolled in the study, 133 from Bissau and 400 from Malakal; 30 were excluded. Confirmation of tuberculosis was achieved in 75 (14.1%), while 248 (46.5%) had unconfirmed tuberculosis. Of 553 with an RS specimen, the overall diagnostic yield was 12.4% (66 of 533). A total of 493 stool and 524 urine samples were used to evaluate the performance of Xpert-Ultra with these samples. Compared with the RS, the sensitivity and specificity of Xpert-Ultra were 62.5% (95% confidence interval, 49.4%–74%) and 98.3% (96.7%–99.2%), respectively, with stool samples, and 13.9% (7.5%–24.3%) and 99.4% (98.1%–99.8%) with urine samples. Nine patients were positive with stool and/or urine samples but negative with the RS. Conclusions Xpert-Ultra in stool samples showed moderate to high sensitivity and high specificity compared with the RS and an added diagnostic yield when RS results were negative. Xpert-Ultra in stool samples was useful in extrapulmonary cases. Xpert-Ultra in urine samples showed low test performance. Clinical Trials Registration NCT06239337
Understanding the impact of modiolus porosity on stimulation of spiral ganglion neurons by cochlear implants
2024-04-26

Abstract Moderate-to-profound sensorineural hearing loss in humans is treatable by electrically stimulating the auditory nerve (AN) with a cochlear implant (CI). In the cochlea, the modiolus presents a porous bony interface between the CI electrode and the AN. New bone growth caused by the presence of the CI electrode or neural degeneration inflicted by ageing or otological diseases might change the effective porosity of the modiolus and, thereby, alter its electrical material properties. Using a volume conductor description of the cochlea, with the aid of a ‘mapped conductivity’ method and an ad-hoc ‘regionally kinetic’ equation system, we show that even a slight variation in modiolus porosity or pore distribution can disproportionately affect AN stimulation. Hence, because of porosity changes, an inconsistent CI performance might occur if neural degeneration or new bone growth progress after implantation. Appropriate electrical material properties in accordance with modiolar morphology and pathology should be considered in patient-specific studies. The present first-of-its-kind in-silico study advocates for contextual experimental studies to further explore the utility of modiolus porous morphology in optimising the CI outcome.
Tectonic imprints in Permian paleomagnetic data of Morocco
2024-04-26

Although Pangea as Earth's youngest supercontinent has continuously served as a pivotal reference mark in paleogeographic reconstructions, its assembly is still a matter of debate. This is mainly due to poor paleomagnetic data coverage for Permian times for Africa, core element of Pangea. Paleomagnetic data from Adria, thought to be the African promontory in the Permian, yield paleolatitudes which, when compared to the European data set, result in a significant continental overlap and seem to confirm the original Pangea B concept of Irving (1977). In order to improve the paleomagnetic data situation for Africa, volcanic and sedimentary rocks were sampled in the Permo-Carboniferous basins of Morocco, yielding a total of 97 sites and 615 samples. Rock magnetic results are diagnostic for magnetite and hematite in various proportions as main carriers of the paleomagnetic signal. After removal of low and intermediate coercivity/blocking temperature components a characteristic component of magnetization pointing to the SE with declinations strung out along a small circle from 107° to 182° and with inclinations around −7° after tectonic correction was identified in 76% of the samples. In nine out of the ten basins studied, positive inclination only fold tests support the primary character of magnetization. Furthermore, three reversals were identified at the basins of M'Tal, Chougrane and Souk El Had Bouhsoussene lending further support to our interpretation of primary magnetization. VGPs are distributed along a NE-SW trending small circle band intersecting the Late Paleozoic segment of the Gondwana APWP with a rotation pole located in the sampling area. The resulting paleolatitudes yield a position of the Meseta block close to the paleo-equator at ∼280 Ma. The widespread presence of vertical axis rotations in the Meseta basins on the other hand, could be related to proposed intra-Pangea shear zones and would provide additional constraints on the extent of such shear zones towards the northern margin of Gondwana. However, tectonic models based on vertical axis rotations in this region need to be treated with caution, since the timing of these rotations remains ambiguous with the current data situation. Using our paleomagnetic data from the Meseta block as representative for Gondwana, a large latitudinal overlap between Gondwana and Laurussia is not required.
A shade-responsive microProtein in the Arabidopsis ATHB2 gene regulates elongation growth and root development
2024-04-26

Abstract The ability of plants to thrive under suboptimal light conditions, such as shade, is crucial for their overall survival and reproductive success. Here, we show that Arabidopsis seedlings produce a large number of alternative transcripts when exposed to shade. Notably, one of the identified transcript candidates, which was upregulated in shade conditions, was found to be an alternative transcript of the ATHB2 gene. ATHB2 belongs to the HD-ZIPII class of transcription factors and is a well-established regulator of the shade avoidance response. The function of the alternative transcript and the small leucine zipper protein encoded by it, ATHB2miP, was investigated. We found that ATHB2miP is primarily expressed in the shoot meristem and interacts with full-length ATHB2 protein to inhibit its activity through a negative feedback mechanism. Deletion of the genomic region encoding the leucine zipper domain of the ATHB2 gene using CRISPR, resulted in plants exhibiting altered shade avoidance responses and root development. We show that the leucine zipper domain is required for dimerising and localising to nuclear photobodies. There is a significant overlap in deregulated genes between plants ectopically expressing ATHB2miP and athb2 mutant plants. The analysis of gene ontology and clustering revealed that the most affected processes are auxin synthesis and signaling, root development, and iron homeostasis. Shade growth experiments at different iron concentrations revealed a role for ATHB2 in regulating iron uptake and showed that iron availability affects shade growth in an ATHB2-dependent manner. This study identifies ATHB2miP as a novel regulator of shade avoidance responses in Arabidopsis, highlighting the intricate transcriptional regulation underlying these processes.
Author response: Asymmetric distribution of color-opponent response types across mouse visual cortex supports superior color vision in the sky
2024-04-26

Color is an important visual feature that informs behavior, and the retinal basis for color vision has been studied across various vertebrate species. While we know how color information is processed in visual brain areas of primates, we have limited understanding of how it is organized beyond the retina in other species, including most dichromatic mammals. In this study, we systematically characterized how color is represented in the primary visual cortex (V1) of mice. Using large-scale neuronal recordings and a luminance and color noise stimulus, we found that more than a third of neurons in mouse V1 are color-opponent in their receptive field center, while the receptive field surround predominantly captures luminance contrast. Furthermore, we found that color-opponency is especially pronounced in posterior V1 that encodes the sky, matching the statistics of natural scenes experienced by mice. Using unsupervised clustering, we demonstrate that the asymmetry in color representations across cortex can be explained by an uneven distribution of green-On/UV-Off color-opponent response types that are represented in the upper visual field. This type of color-opponency in the receptive field center of V1 neurons was not present in the receptive field center of retinal ganglion cells and, therefore, is likely computed by integrating center and surround information down-stream of the retina. Finally, a simple model with natural scene-inspired parametric stimuli shows that green-On/UV-Off color-opponent response types may enhance the detection of "predatory"-like dark UV-objects in noisy day-light scenes. The results from this study highlight the relevance of color processing in the mouse visual system and contribute to our understanding of how color information is organized in the visual hierarchy across species. More broadly, they support the hypothesis that the visual cortex combines upstream information towards computing neuronal selectivity to behaviorally-relevant sensory features.
Structural insights into the GTP-driven monomerization and activation of a bacterial LRRK2 homolog using allosteric nanobodies
2024-04-26

Roco proteins entered the limelight after mutations in human LRRK2 were identified as a major cause of familial Parkinson’s disease. LRRK2 is a large and complex protein combining a GTPase and protein kinase activity, and disease mutations increase the kinase activity, while presumably decreasing the GTPase activity. Although a cross-communication between both catalytic activities has been suggested, the underlying mechanisms and the regulatory role of the GTPase domain remain unknown. Several structures of LRRK2 have been reported, but structures of Roco proteins in their activated GTP-bound state are lacking. Here, we use single-particle cryo-electron microscopy to solve the structure of a bacterial Roco protein (CtRoco) in its GTP-bound state, aided by two conformation-specific nanobodies: Nb Roco1 and Nb Roco2 . This structure presents CtRoco in an active monomeric state, featuring a very large GTP-induced conformational change using the LRR-Roc linker as a hinge. Furthermore, this structure shows how Nb Roco1 and Nb Roco2 collaborate to activate CtRoco in an allosteric way. Altogether, our data provide important new insights into the activation mechanism of Roco proteins, with relevance to LRRK2 regulation, and suggest new routes for the allosteric modulation of their GTPase activity.
Asymmetric distribution of color-opponent response types across mouse visual cortex supports superior color vision in the sky
2024-04-26

Color is an important visual feature that informs behavior, and the retinal basis for color vision has been studied across various vertebrate species. While we know how color information is processed in visual brain areas of primates, we have limited understanding of how it is organized beyond the retina in other species, including most dichromatic mammals. In this study, we systematically characterized how color is represented in the primary visual cortex (V1) of mice. Using large-scale neuronal recordings and a luminance and color noise stimulus, we found that more than a third of neurons in mouse V1 are color-opponent in their receptive field center, while the receptive field surround predominantly captures luminance contrast. Furthermore, we found that color-opponency is especially pronounced in posterior V1 that encodes the sky, matching the statistics of natural scenes experienced by mice. Using unsupervised clustering, we demonstrate that the asymmetry in color representations across cortex can be explained by an uneven distribution of green-On/UV-Off color-opponent response types that are represented in the upper visual field. This type of color-opponency in the receptive field center of V1 neurons was not present in the receptive field center of retinal ganglion cells and, therefore, is likely computed by integrating center and surround information down-stream of the retina. Finally, a simple model with natural scene-inspired parametric stimuli shows that green-On/UV-Off color-opponent response types may enhance the detection of “predatory”-like dark UV-objects in noisy day-light scenes. The results from this study highlight the relevance of color processing in the mouse visual system and contribute to our understanding of how color information is organized in the visual hierarchy across species. More broadly, they support the hypothesis that the visual cortex combines upstream information towards computing neuronal selectivity to behaviorally-relevant sensory features.
Can't help processing numbers with text: Eye-tracking evidence for simultaneous instead of sequential processing of text and numbers in arithmetic word problems
2024-04-26

Solving arithmetic word problems requires individuals to create a correct mental representation, and this involves both text processing and number processing. The latter comprises understanding the semantic meaning of numbers (i.e., their magnitudes) and potentially executing the appropriate mathematical operation. However, it is not yet clear whether number processing occurs after text processing or both take place simultaneously. We hypothesize that number processing occurs early and simultaneously with other problem-solving processes such as text processing. To test this hypothesis, we created non-solvable word problems that do not require any number processing and we manipulated the calculation difficulty using carry/borrow vs. non-carry/non-borrow within addition and subtraction problems. According to a strictly sequential model, this manipulation should not matter, because the problem is non-solvable, and no calculation is required. In contrast, according to an interactive model, attention to numbers would be higher when word problems require a carry/borrow compared to a non-carry/non-borrow operation. Eye-tracking was used to measure attention to numbers and text in 63 adults, operationalized by static (duration and count of fixations and regressions) and dynamic measures (count of transitions). An interaction between difficulty and operation was found for all static and dynamic eye-tracking variables as well as for response times and error rates. The observed number processing in non-solvable word problems, which indicates that it occurs simultaneously with text processing, is inconsistent with strictly sequential models.
The complexity of human subjective experience during binocular rivalry
2024-04-26

Our subjective experience of the sensory information is rich and complex. Yet, typical cognitive and perception psychology paradigms reduce it to a few pre-defined discrete categories, like yes/no answers or the Likert scales. In the current study, we examined the complexity of subjective visual experience during binocular rivalry, a major experimental paradigm used to study conscious visual perception and its neural mechanisms. Binocular rivalry occurs when the two eyes are presented with two different images that cannot be fused into a uniform percept. As a result, the conscious perception alternates between the two images with brief transition phases in-between. Fifty-two subjects viewed binocular rivalry produced by pairs of stimuli with different visual information (images, orthogonal gratings or moving dots). After each rivalry period, they indicated how many different transition types they perceived and described their perception of each transition type. Using content analysis we identified 20 unique categories over all subjects, sessions, and stimuli. On average, participants reported 2-3 unique transition categories for each visual stimulus combination. The categories were consistent for each observer over time but varied across participants and stimulus content. Our results show that perceptual transitions during binocular rivalry appear in different forms and depend on the specific visual stimulus content that induces rivalry. Our findings have implications for neuroimaging studies of binocular rivalry, which may yield different results depending on the exact experience of transitions. They also demonstrate how the complexity of subjective visual experience may be underestimated in traditional perception paradigms.
Reliability in Machine Learning
2024-04-27

Abstract Issues of reliability are claiming center‐stage in the epistemology of machine learning. This paper unifies different branches in the literature and points to promising research directions, whilst also providing an accessible introduction to key concepts in statistics and machine learning – as far as they are concerned with reliability.