Miracle-dz/UniFAR-FTUs huggingface dataset:
Partial RNA Design

RNA design is a key technique to achieve new functionality in fields like synthetic biology or biotechnology. Computational tools could help to find such RNA sequences but they are often limited in their formulation of the search space. In this work, we propose partial RNA design, a novel RNA design paradigm that addresses the limitations of current RNA design formulations. Partial RNA design describes the problem of designing RNAs from arbitrary RNA sequences and structure motifs with multiple design goals. By separating the design space from the objectives, our formulation enables the design of RNAs with variable lengths and desired properties, while still allowing precise control over sequence and structure constraints at individual positions. Based on this formulation, we introduce a new algorithm, libLEARNA, capable of efficiently solving different constraint RNA design tasks. A comprehensive analysis of various problems, including a realistic riboswitch design task, reveals the outstanding performance of libLEARNA and its robustness.
Gliogenesis from the subventricular zone modulates the extracellular matrix at the glial scar after brain ischemia

Activation of the subventricular zone (SVZ) after cerebral ischemia is one of the early responses in the brain to counteract the loss of neurons and reduce tissue damage. Impaired brain regions communicate with the SVZ through many chemotactic messages that result in neural stem cells (NSC) migration and differentiation. However, the activation of gliogenesis and the role of newborn astrocytes in the post-ischemic scenario is still under debate. We have previously shown that adenosine release after brain ischemia prompts the SVZ to generate new astrocytes. Here, we use transient brain ischemia in mice to define the cellular origin of these astrocytes in the SVZ neurogenic niche and investigate their role in the pathological process. By combining immunofluorescence, BrdU-tracing and genetic cellular labelling, we tracked the migration of newborn astrocytes, positive for the proteoglycan marker Thbs4, from the dorsal and medial SVZ to the perilesional barrier surrounding the ischemic core, termed “glial scar”. We found that these Thbs4-positive astrocytes modulate the dense extracellular matrix at the lesion border by synthesis but also degradation of hyaluronan. We also show that while the accumulation of this polymer at the lesion is sufficient to recruit newborn astrocytes, its degradation at the SVZ correlates with gliogenesis. These results point to newborn astrocytes as a plausible pharmacological target to modulate the glial scar after brain ischemia and facilitate tissue regeneration.
Diversity and connectivity of principal neurons in the lateral and basal nuclei of the mouse amygdala

The basolateral amygdala is a non-layered cortical structure playing a role in various cognitive processes. Despite many studies focusing on local information processing within the circuits of the basolateral amygdala, the characteristics of excitatory principal neurons (PNs) are still not fully revealed. Here, we combined neuroanatomical, electrophysiological, and tracing techniques to determine the single-cell features, dendritic and axonal projections of PNs within the lateral (LA) and basal amygdala (BA). Using a mouse reporter line, we found that cholecystokinin (CCK) expression defines two spatially and functionally segregated groups of PNs both in the LA and BA. PNs in CCK-positive (CCK+) areas of the LA (LAa) had small somata and short dendrites which matched their single-cell electrophysiological properties. PNs in CCK-negative (CCK-) areas of the LA (LAp) and all BA had similarly ramified dendrites and single-cell features with some differences. Importantly, the dendritic arbors of PNs were restricted to the subnuclei defined by CCK expression, which corresponded to various extra-amygdalar afferents indicating specific inputs on distinct PN groups. Axonal arborization patterns of PNs within the basolateral amygdala and surrounding areas showed consistency to their soma location. For instance, BA PNs that projected to the medial prefrontal cortex but not to the lateral nucleus of the central amygdala were present in CCK+ areas. In contrast, those BA PNs that projected to the lateral part of the central nucleus were found in the subnucleus lacking CCK. Our study revealed that the basolateral amygdala is composed of functionally different subnuclei with specific inputs and outputs. This structural arrangement may empower the LA and BA to flexibly channel processed information toward their downstream regions, which can be a key requirement for diverse amygdala functions in cognitive operation.
Rapid and specific detection of single nanoparticles and viruses in microfluidic laminar flow via confocal fluorescence microscopy

Mainstream virus detection relies on the specific amplification of nucleic acids via polymerase chain reaction, a process that is slow and requires extensive laboratory expertise and equipment. Other modalities, such as antigen-based tests, allow much faster virus detection but have reduced sensitivity. In this study, we report the development of a flow virometer for the specific and rapid detection of single nanoparticles based on confocal microscopy. The combination of laminar flow and multiple dyes enable the detection of correlated fluorescence signals, providing information on nanoparticle volumes and specific chemical composition properties, such as viral envelope proteins. We evaluated and validated the assay using fluorescent beads and viruses, including SARS-CoV-2. Additionally, we demonstrate how hydrodynamic focusing enhances the assay sensitivity for detecting clinically-relevant virus loads. Based on our results, we envision the use of this technology for clinically relevant bio-nanoparticles, supported by the implementation of the assay in a portable and user-friendly setup.
Trivalent mRNA vaccine-candidate against seasonal flu with cross-specific humoral immune response

Seasonal influenza remains a serious global health problem, leading to high mortality rates among the elderly and individuals with comorbidities. It also imposes a substantial economic burden through increased absenteeism during periods of active pathogen circulation. Vaccination is generally accepted as the most effective strategy for influenza prevention. As both influenza A and B viruses circulate and cause seasonal epidemics, vaccines need to include multiple antigens derived from different viral subtypes. While current influenza vaccines are effective, they still have limitations, including narrow specificity for certain serological variants, which may result in a mismatch between vaccine antigens and circulating strains. Additionally, the rapid variability of the virus poses challenges in providing extended protection beyond a single season. Therefore, mRNA technology is particularly promising for influenza prevention, as it enables the rapid development of multivalent vaccines and allows for quick updates of their antigenic composition. mRNA vaccines have already proven successful in preventing COVID-19 by eliciting rapid cellular and humoral immune responses. In this study, we present the development of a trivalent mRNA vaccine candidates, evaluate its immunogenicity using the hemagglutination inhibition assay, and assess its efficacy in animals. We demonstrate the higher immunogenicity of the mRNA vaccine candidates compared to the inactivated split influenza vaccine and its enhanced ability to generate a cross-specific humoral immune response. These findings highlight the potential mRNA technology in overcoming current limitations of influenza vaccines and hold promise for ensuring greater efficacy in preventing seasonal influenza outbreaks.
Transient power-law behaviour following induction distinguishes between competing models of stochastic gene expression

What features of transcription can be learnt by fitting mathematical models of gene expression to mRNA count data? Given a suite of models, fitting to data selects an optimal one, thus identifying a probable transcriptional mechanism. Whilst attractive, the utility of this methodology remains unclear. Here, we sample steady-state, single-cell mRNA count distributions from parameters in the physiological range, and show they cannot be used to confidently estimate the number of inactive gene states, i.e. the number of rate-limiting steps in transcriptional initiation. Distributions from over 99% of the parameter space generated using models with 2, 3, or 4 inactive states can be well fit by one with a single inactive state. However, we show that if the mRNA lifetime is hours long, then for many minutes following induction, the increase in the mean mRNA count obeys a power law whose exponent equals the sum of the number of states visited from the initial inactive state to the active state and the number of rate-limiting post-transcriptional processing steps. Our study shows that non-linear regression estimation of the exponent from eukaryotic data is sufficient to estimate the total number of regulatory steps in transcription initiation, splicing, and nuclear export.
Cell density couples tissue mechanics to control the elongation speed of the body axis

The vertebrate body forms by progressive addition and segmentation of tissues in an anterior to posterior direction. The posterior presomitic mesoderm (pPSM), which receives new cells from the tailbud, produces an expansive force that drives axis elongation1–3. Elongation moves an FGF gradient that controls the boundary placement of new segments in conjunction with the oscillatory genes of the segmentation clock4. As the period of the segmentation clock is insensitive to body size5,6 or elongation progress7,8, the number and size consistency of segments depend on stable, robust elongation. How elongation speed is constrained remains unknown. Here we utilised modeling and tissue force microscopy9 on chicken embryos to show that cell density of the pPSM dynamically modulates elongation speed in a negative feedback loop. Elongation alters the cell density in the pPSM, which in turn controls progenitor cell influx through the mechanical coupling of body axis tissues. This enables responsive cell dynamics in over- and under-elongated axes that consequently self-adjust speed to achieve long-term robustness in axial length. Our simulations and experiments further suggest that cell density and activity under FGF signalling act synergistically to drive elongation. Our work supports a simple mechanism of morphogenetic speed control where the cell density relates negatively to progress, and positively to force generation.
The Primary Function of MTL is Memory, not Navigation: Grid Cells are Non-spatial (what) and Place Cells are Memories (what and where) that Cause Grid Fields through Retrieval

A theory and neurocomputational model are presented that explain grid cell responses as the byproduct of equally dissimilar hippocampal memories. On this account, place and grid cells are not best understood as providing a navigational system. Instead, place cells represent memories that are conjunctions of both spatial and non-spatial attributes, and grid cells primarily represent the non-spatial attributes (e.g., odors, surface texture, etc.) found throughout the two-dimensional recording enclosure. Place cells support memories of the locations where non-spatial attributes can be found (e.g., positions with a particular odor), which are arranged in a hexagonal lattice owing to memory encoding and consolidation processes (pattern separation) as applied to situations in which the non-spatial attributes are found at all locations of a two-dimensional surface. Grid cells exhibit their spatial firing pattern owing to feedback from hippocampal place cells (i.e., a hexagonal pattern of remembered locations for the non-spatial attribute represented by a grid cell). The model explains: 1) grid fields that appear to be centered outside the box; 2) the toroidal nature of grid field representations; 3) grid field alignment with the enclosure borders; 4) modules in which grid cells have the same orientation and spacing but different phases; 5) head direction conjunctive grid cells that become simple head direction cells in the absence of hippocampal feedback; 6) the instant existence of grid fields in a novel environment; 7) the slower learning of place cells; 8) the manner in which head direction sensitivity of place cells changes near borders and in narrow passages; 9) the kinds of changes that underlie remapping of place cells; and 10) grid-like responses for two-dimensional coordinate systems other than navigation.
Genome-wide characterisation of pathogenicity-related proteins in Mycena citricolor, the causal agent of the American Leaf Spot in coffee

Mycena citricolor is a fungus that causes the American Leaf Spot (ALS) disease in multiple hosts, including coffee and avocado. This hemibiotroph penetrates the plant through damage induced by oxalic acid. This can cause 20-90% crop losses in coffee depending on the environmental and production conditions. M. citricolor is the only known pathogenic species in the Mycena genus, a large group of saprophytic mushrooms. Comparing the saprophytic and pathogenic genomes can allow us to identify genetic machinery associated with the pathogen’s genome-wide functional acquisitions to cause disease. To identify pathogenicity-related genes in M. citricolor, we analysed protein family copy-number variation, secretome prediction, and homology to known virulence factors in two M. citricolor assemblies, including a newly assembled and annotated long-read genome. We found that the pathogenic M. citricolor had a higher proportion of secreted genes expanded in copy-number, and expanded gene copies homologous to known virulence factors than the saprophytic Mycena. We shortlisted over 300 candidate genes in each M. citricolor assembly. Focusing on genes strongly regulated during plant interaction, we found over 100 candidates, primarily from multiple copies (up to 4-3 times) of 42 well-known virulence factors (e.g. MFS1, CUTA, NoxA/B, OLE1, NorA), plus a few clade-specific uncharacterised genes. M. citricolor transition to a pathogenic lifestyle reflected genome-wide functional changes. M. citricolor seems to primarily depend on well-known virulence factors in large copy numbers, suggesting the molecular plant-interaction processes involved are like those of better-studied fungi. Hypothetically, the development of ALS resistance could mirror studied responses to these virulence factors.
Identifying Individual Changes in Race and Ethnicity: An Example from U.S. Panel Data, 1880-1940 (Very Preliminary)

This paper investigates the fluidity of ethnic identity and the extent to which individuals experience a change in reported ethnicity during their lifetime in the historical U.S. context. First, we document that approximately 21 to 22% of males identified as mixed race and 16 to 17% of males identified as black will “pass” for white at some point in their lifetime. Second, we show that passing is almost always accompanied by geographic relocation and typically occurs when an individual is twenty to thirty years of age. Third, by tracing an individual over time, we find that a significant number of those who pass for white will later “un-pass”. Finally, imputed wage data suggests that the probability of passing is positively correlated with the black-white wage gap in the county of birth. Our results indicate race is fluid, race change is a quantitatively important phenomenon and likely to be endogenous to economic variables.
SYSTEMI - Systemic organ communication in STEMI: Design and rationale of a cohort study of patients with ST-segment elevation myocardial infarction

Background: (335/350) ST-segment elevation myocardial infarction (STEMI) still causes significant mortality and morbidity despite best-practice revascularization and adjunct medical strategies. Within the STEMI population, there is a spectrum of higher and lower risk patients with respect to major adverse cardiovascular and cerebral events (MACCE) or re-hospitalization due to heart failure. Myocardial and systemic metabolic disorders modulate patient risk in STEMI. Systematic cardiocirculatory and metabolic phenotyping to assess the bidirectional interaction of cardiac and systemic metabolism in myocardial ischemia is lacking. Methods: Systemic organ communication in STEMI (SYSTEMI) is an all-comer open-end prospective study in STEMI patients >18 years of age to assess the interaction of cardiac and systemic metabolism in STEMI by systematically collecting data on a regional and systemic level. Primary endpoint will be myocardial function, left ventricular remodelling, myocardial texture and coronary patency at 6 month after STEMI. Secondary endpoint will be all-cause death, MACCE, and re-hospitalisation due to heart failure or revascularisation assessed 12 month after STEMI. The objective of SYSTEMI is to identify metabolic systemic and myocardial master switches that determine primary and secondary endpoints. In SYSTEMI 150-200 patients are expected to be recruited per year. Patient data will be collected at the index event, within 24 hours, 5 days as well as 6 and 12 months after STEMI. Data acquisition will be performed in multilayer approaches. Myocardial function will be assessed by using serial cardiac imaging with cineventriculography, echocardiography and cardiovascular magnetic resonance. Myocardial metabolism will be analysed by multi-nuclei magnetic resonance spectroscopy. Systemic metabolism will be approached by serial liquid biopsies and analysed with respect to glucose and lipid metabolism as well as oxygen transport. In summary, SYSTEMI enables a comprehensive data analysis on the levels of organ structure and function alongside hemodynamic, genomic and transcriptomic information to assess cardiac and systemic metabolism. Discussion: SYSTEMI aims to identify novel metabolic patterns and master-switches in the interaction of cardiac and systemic metabolism to improve diagnostic and therapeutic algorithms in myocardial ischemia for patient-risk assessment and tailored therapy.
Pregnancy Outcomes After a Long Amnioinfusion Via Subcutaneously Implanted Port System in Women with Preterm Rupture of Membranes with Oligo-And Agidramnionom At 22-27 Weeks Of Gestation.

Preterm premature rupture of membranes (PPROM) represents one of the main causes of high neonatal mortality and morbidity. Amnitotic fluid loss with oligo/ anhydramnios is associated with extreme preterm birth, pulmonar y hypoplasia and the „fetal inflammatory response syndrome“ (FIRS). About 40% of these extreme preterm delivery children die during next 5 years. Preterm birth, for those babies who remain alive, is in higher risk of disability, which surely burdensome for families and health care’s system. The aim of the study was to prolong the PPROM-delivery interval without to increase the risk of FIRS using continuous amnioinfusion with artificial amniotic fluid “flush out” therapy, through a subcutaneously implanted p ort-system. The 11 patients were carefully
Modeling two-qubit Grover’s algorithm implementation in a linear optical chip

This paper introduces a model of Grover’s algorithm suitable for implementation in a linear photonic chip. We compare two known realizations of its main components, two-qubit CZ gates, in order to define optimal chip architecture. The algorithm operation is simulated considering directional coupler imperfection influence on the scheme parameters. We also determined tolerance boundaries for distortions of the coupler dimensions.
Psychometric Evaluation of the Chinese Version of the Resilience Scale for Children with Cancer

Background: To test the psychometric properties of a traditional Chinese version of the Resilience Scale for Children (RS-10) and examine its factorial structure via a confirmatory factor analysis (CFA). Methods: One hundred and eighty-six Hong Kong Chinese children with cancer were recruited in the paediatric oncology units of two public acute-care hospitals in Hong Kong to participate in this cross-sectional study. The psychometric properties of the traditional Chinese version of the RS-10 were assessed, namely its content validity, convergent and discriminant validity, construct validity, internal consistency and test–retest reliability.Results: The newly translated traditional Chinese version of the RS-10 demonstrated adequate internal consistency, excellent test–retest reliability, good content validity and appropriate convergent and discriminant validity. The CFA results demonstrated that there was a good fit between the factor structure of the Chinese version of the RS-10 and the observed data, thereby confirming the construct validity of this instrument.Conclusions: The traditional Chinese version of the RS-10 was found to be a reliable and valid tool for assessing the resilience of Hong Kong Chinese children with cancer. The newly developed traditional Chinese version of the RS-10 is an appropriate clinical research tool for evaluating the effectiveness of nursing interventions in enhancing the resilience of and promoting mental well-being in children with cancer. Trial registration: NCT03544190
Geometry and kinematics of the Triassic rift basin in Jameson Land (East Greenland)

The Triassic rift basin along the east Greenland margin described in this paper is represented by NE‐SW trending basins and highs segmented by NW‐SE trending transfer zones. Coarse‐grained sediments along the eastern side of Jameson Land are shown to be hosted in half‐graben structures belonging to the Carlsberg Fjord Basin that is bounded by NW dipping normal faults mapped and described after fieldwork in the Klitdal area in Liverpool Land. New aeromagnetic and electromagnetic data together with new drill cores allow the reinterpretation of available seismic lines showing the continuation of the Triassic rift basin toward the SW where it is buried under the Upper Triassic postrift sediments and the Jurassic successions of the Jameson Land Basin. The N‐S trending Liverpool Land, interpreted as the boundary block of the Triassic basin, is shown to represent a structural high inherited from the Late Carboniferous tectonics and faulted during the Triassic rifting. The Carlsberg Fjord Basin and the Klitdal Fault System described in this paper should be seen as analogues to the Helgeland Basin in the Norwegian offshore that is bounded by the Ylvingen Fault Zone and to the Papa and West of Shetlands Basins that are bounded by the Spine Fault. The Triassic rift zone and transfer faults on both conjugate margins show a straightforward correlation with the trends of the initial spreading line and fracture zones of the northeast Atlantic indicating a possible inheritance of the Triassic rifting.