Miracle-dz/UniFAR-FTUs huggingface dataset:
From gas to sugar: Trehalose production in Cupriavidus necator from CO2 and hydrogen gas

The paradigm of a fossil based, non-renewable economy will have to change in the future due to environmental concerns and the inevitable depletion of resources. Therefore, the way we produce and consume chemicals has to be rethought: The bio-economy offers such a concept for the sustainable production of commodity chemicals using waste streams or renewable electricity and CO2. Residual biomass or organic wastes can be gasified to energy rich mixtures that in turn can be used for synthesis gas fermentation. Within this scope, we present a new process for the production of trehalose from gaseous substrates with the hydrogen-oxidizing bacterium Cupriavidus necator H16. We first show that C. necator is a natural producer of trehalose, accumulating up to 3.6% of its cell dry weight as trehalose when stressed with 150 mM sodium chloride. Bioinformatic investigations revealed a so far unknown mode of trehalose and glycogen metabolism in this organism. Next, we evaluated different concepts for the secretion of trehalose and found that expression of the sugar efflux transporter A (setA) from Escherichia coli was able to lead to a trehalose-leaky phenotype. Finally, we characterized the strain under autotrophic conditions using a H2/CO2/O2-mixture and other substrates. Even without overexpressing trehalose synthesis genes, titers of 0.47 g/L and yields of around 10% were reached, which shows the great potential of this process. Taken together, this process represents a new way to produce sugars with a higher areal efficiency than photosynthesis by crop plants. With further metabolic engineering, we anticipate an application of this technology for the renewable production of trehalose and other sugars, as well as for the synthesis of 13C-labeled sugars. Graphical abstract
In vitro endoderm emergence and self-organisation in the absence of extraembryonic tissues and embryonic architecture

The endoderm is the cell lineage which gives rise in the embryo to the organs of the respiratory and gastrointestinal system. Uniquely, endodermal tissue does not just derive from descendants of the embryo proper (the epiblast) but instead arises from their gradual incorporation into an extraembryonic substrate (the visceral endoderm). Given the configuration of the early embryo, such a paradigm requires epiblast endodermal progenitors to negotiate embryonic compartments with very diverse epithelial character, a developmental contingency reflected by the fact that key early endodermal markers such as Foxa2 and Sox17 have been consistently found to be embedded within gene programmes involved in epithelialisation. To explore the underlying cell biology of embryonic endoderm precursors, and to explore the relationship between endoderm development, epithelial identity, and extraembryonic mixing, we leveraged Gastruloids, in vitro models of early development. These self-organising three-dimensional aggregates of mouse embryonic stem cells do not possess an extraembryonic component, nor do they appear to display typical tissue architecture. Yet, they generate cells expressing endodermal markers. By tracking these cells throughout in vitro development, we highlight a persistent and uninterrupted pairing between epithelial and endodermal identity, with FoxA2+/Sox17+ endoderm progenitors never transitioning through mesenchymal intermediates and never leaving the epithelial compartment in which they arise. We also document the dramatic morphogenesis of these progenitors into a macroscopic epithelial primordium extending along the entire anterior-posterior axis of the Gastruloid. Finally, we find that this primordium correctly patterns into broad domains of gene expression, and matures cells with anterior foregut, midgut, and hindgut identities within 7 days of culture. We thus postulate that Gastruloids may serve as a potential source of endodermal types difficult to obtain through classical 2D differentiation protocols.
Feature Extraction Approaches for Biological Sequences: A Comparative Study of Mathematical Models

The number of available biological sequences has increased significantly in recent years due to various genomic sequencing projects, creating a huge volume of data. Consequently, new computational methods are needed to analyze and extract information from these sequences. Machine learning methods have shown broad applicability in computational biology and bioinformatics. The utilization of machine learning methods has helped to extract relevant information from various biological datasets. However, there are still several obstacles that motivate new algorithms and pipeline proposals, mainly involving feature extraction problems, in which extracting significant discriminatory information from a biological set is challenging. Considering this, our work proposes to study and analyze a feature extraction pipeline based on mathematical models (Numerical Mapping, Fourier, Entropy, and Complex Networks). As a case study, we analyze Long Non-Coding RNA sequences. Moreover, we divided this work into two studies, e.g., (I) we assessed our proposal with the most addressed problem in our review, e.g., lncRNA vs. mRNA; (II) we tested its generalization on different classification problems, e.g., circRNA vs. lncRNA. The experimental results demonstrated three main contributions: (1) An in-depth study of several mathematical models; (2) a new feature extraction pipeline and (3) its generalization and robustness for distinct biological sequence classification.
Context Sensitivity Across Multiple Time and Frequency Scales

Everyday auditory stimuli contain structure at multiple time and frequency scales. Using EEG, we demonstrate sensitivity of human auditory cortex to the content of past stimulation in unattended sequences of equiprobable tones. In 3 experiments including 79 participants overall, we found that at different latencies after stimulus onset, neural responses were sensitive to frequency intervals computed over distinct time scales. To account for these results, we tested a model consisting of neural populations with frequency-specific but broad tuning that undergo adaptation with exponential recovery. We found that the coexistence of neural populations with distinct recovery rates can explain our results. Furthermore, the adaptation bandwidth depends on spectral context – it is wider when the stimulation sequence has a wider frequency range. Our results provide electrophysiological evidence as well as a possible mechanistic explanation for dynamic and multi-scale context-dependent auditory processing in the human cortex.
A Program for Efficient Phasing of Three-Generation Trio SNP Genotype Data

Here, we report a computer program written in Python, which phases SNP genotypes and infers inherited deletions based on the pattern of Mendelian inheritance within a trio pedigree. When tiered trio genotypes that encompass three generations are available, it narrows a recombination event down to a region between two consecutive heterozygous markers. In addition, the phase information that is inferred from the upper trio that is formed by one of the parents and grandparents can be propagated to phase the genotypes of the lower trio that is formed by the parents and an offspring.
Recurrent Dynamics of Rupture Transitions of Single Giant Vesicles at Solid Surfaces

Single giant vesicles (GVs) rupture spontaneously from their salt-laden suspension onto solid surfaces. At hydrophilic surfaces, they rupture via a recurrent burst-heal dynamics: during burst, single pores nucleate at the contact boundary of the adhering vesicles facilitating asymmetric spreading and producing a “heart” shaped membrane patch. During the healing phase, the competing pore closure produces a daughter vesicle. At hydrophobic surfaces, by contrast, the GVs rupture via a distinctly different, yet recurrent, bouncing ball rhythm: Rendered tense by the substrate interactions, GVs porate and spread monomolecular layer on the hydrophobic surface in a symmetric manner. Here too, the competition from pore closure produces a daughter vesicle, which re-engages with the substrate. In both cases, the pattern of burst-reseal events repeats multiple times splashing and spreading the vesicular fragments as bilayer patches at the solid surface in a pulsatory manner. These remarkable recurrent dynamics arise not because of the elastic properties of the solid surface but because the competition between membrane spreading and pore healing, prompted by the surface-energy dependent adhesion, determine the course of the topological transition. STATEMENT OF SIGNIFICANCE Giant lipid vesicles adhering to a solid surface experience strong mechanical stresses. The contacting membrane segment loses thermal fluctuations and accumulates mechanical tension, the equilibration of which can give rise to global shape changes, lipid phase separation, and traction forces. Beyond a threshold tension, vesicles porate, unravel, and spread. Here, we find that a competition from pore-healing can make rupture iterative, rather than a single all-or-nothing event. During burst, single pores expand, spreading a lipid bilayer on the hydrophilic surface and a monolayer on the hydrophobic one. During heal, pore-healing can produce daughter vesicles. This burst-reseal event reiterates “splashing” portions of single vesicles at the solid surface and “bouncing” the remainder as a secondary vesicle in multiple steps.
The hypothalamus as a hub for putative SARS-CoV-2 brain infection

Most patients with COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), display neurological symptoms, and respiratory failure in certain cases could be of extra-pulmonary origin. With reports detecting SARS-CoV-2 in some post-mortem patient brains, the routes, targets and consequences of brain infection merit investigation. Hypothalamic neural circuits play key roles in sex differences, diabetes, hypertension, obesity and aging, all risk factors for severe COVID-19, besides being connected to brainstem cardiorespiratory centers. Here, human brain gene-expression analyses reveal that the hypothalamus and associated regions express angiotensin-converting enzyme 2 and transmembrane proteinase, serine 2, which mediate SARS-CoV-2 cellular entry, in correlation with several genes or pathways involved in physiological functions or viral pathogenesis. Immunolabeling in human and animal brains suggests that the hypothalamus could be central to SARS-CoV-2 brain invasion through multiple routes, and that sex hormones and metabolic diseases influence brain susceptibility.
Syntax-sensitive regions of Broca’s area and the posterior temporal lobe are differentially recruited by production and perception

Neuroimaging studies of syntactic processing typically result in similar activation profiles in Broca’s area and the posterior temporal lobe (PTL). However, substantial functional dissociations between these regions have been demonstrated with respect to lesion-symptom mapping in aphasia. To account for this, Matchin & Hickok (2020) proposed that both regions play a role in syntactic processing, broadly construed, but attribute distinct functions to these regions with respect to production and comprehension. Here we report an fMRI study designed to test this hypothesis by contrasting the subvocal articulation and comprehension of structured jabberwocky phrases (syntactic), sequences of real words (lexical), and sequences of pseudowords (phonological). We defined two sets of language-selective regions of interest (ROIs) in individual subjects for Broca’s area and the PTL using the contrasts [syntactic > lexical] and [syntactic > phonological]. We found robust significant interactions of comprehension and production between these two regions at the syntactic level, for both sets of language-selective ROIs. This suggests a core difference in the function of these regions: language-selective subregions of Broca’s area play a role in syntax driven by the demands of production, whereas language-selective subregions of the PTL play a role in syntax driven by the demands of comprehension.
No modulatory effect of rhythmic visual alpha/gamma stimulation in a bistable motion illusion

The ‘motion quartet’, also called stroboscopic alternative motion (SAM), is a bistable apparent motion paradigm where dots are perceived as moving either horizontally or vertically. These two percepts are known to switch randomly depending on both alpha (8 – 12 Hz) and gamma (30 – 80 Hz) oscillations within and between hemispheres, respectively. However, whether these oscillations play a causal role in triggering perceptual switches remains unknown. Here, we aimed to entrain brain oscillations in the visual system by presenting flickering stimuli. Two LEDs were flickering either at 10 Hz, 40 Hz or corresponding jittered stimulation frequencies on the left and right sides of the visual field during the presentation of a motion quartet. In our control condition (no stimulation), we show that interhemispheric gamma connectivity (spectral coherence) between the visual cortices of both hemispheres is important for sensory feature integration. On the other hand, alpha power did not predict perceptual switches for the motion quartet. Rhythmic visual stimulation with 10 Hz and 40 Hz evoked resonance-like neural responses but did not alter visual perception. Thus, although sensory stimuli seem to entrain ongoing brain rhythms, the effect on human behavior differs from the principles observed for endogenous brain oscillations.
Segmented K-Space Blipped-Controlled Aliasing in Parallel Imaging (Skipped-CAIPI) for High Spatiotemporal Resolution Echo Planar Imaging

Purpose A segmented k-space blipped-CAIPI (skipped-CAIPI) sampling strategy for echo planar imaging (EPI) is proposed, which allows for a flexible choice of EPI factor and phase encode bandwidth independent of the controlled aliasing (CAIPIRINHA) pattern. Theory and Methods With previously proposed approaches, exactly two EPI trajectories were possible given a specific CAIPIRINHA pattern: either with slice gradient blips (blipped-CAIPI), or following a shot-selective approach (higher resolution). Recently, interleaved multi-shot segmentation along shot-selective CAIPI trajectories has been applied for high-resolution anatomical imaging. For more flexibility and a broader range of applications, we propose segmentation along any blipped-CAIPI trajectory. Thus, all EPI factors and phase encode bandwidths available with traditional segmented EPI can be combined with controlled aliasing. Results Temporal signal-to-noise ratios of moderate-to-high-resolution time series acquisitions at varying undersampling factors demonstrate beneficial sampling alternatives to blipped-CAIPI or shot-selective CAIPI. Rapid high-resolution scans furthermore demonstrate SNR-efficient and motion-robust structural imaging with almost arbitrary EPI factor and minimal noise penalty. Conclusions Skipped-CAIPI sampling increases protocol flexibility for high spatiotemporal resolution EPI. In terms of signal-to-noise ratio and efficiency, high-resolution functional or structural scans benefit vastly from a free choice of the CAIPIRINHA pattern. Even at moderate resolutions, the independence of sampling pattern, echo time and image matrix size is valuable for optimized functional protocol design. Although demonstrated with 3D-EPI, skipped-CAIPI is also applicable with simultaneous multislice EPI.
Transgenic goats producing an improved version of cetuximab in milk

Therapeutic monoclonal antibodies (mAbs) represent one of the most important classes of pharmaceutical proteins to treat human diseases. Most are produced in cultured mammalian cells which is expensive, limiting their availability. Goats, striking a good balance between a relatively short generation time and copious milk yield, present an alternative platform for the cost-effective, flexible, large-scale production of therapeutic mAbs. Here, we focused on cetuximab, a mAb against epidermal growth factor receptor, that is commercially produced under the brand name Erbitux and approved for anti-cancer treatments. We generated several transgenic goat lines that produce cetuximab in their milk. Two lines were selected for detailed characterization. Both showed stable genotypes and cetuximab production levels of up to 10g/L. The mAb could be readily purified and showed improved characteristics compared to Erbitux. The goat-produced cetuximab (gCetuximab) lacked a highly immunogenic epitope that is part of Erbitux. Moreover, it showed enhanced binding to CD16 and increased antibody-dependent cell-dependent cytotoxicity compared to Erbitux. This indicates that these goats produce an improved cetuximab version with the potential for enhanced effectiveness and better safety profile compared to treatments with Erbitux. In addition, our study validates transgenic goats as an excellent platform for large-scale production of therapeutic mAbs.
Atrophy associated with tau pathology precedes overt cell death in a mouse model of progressive tauopathy

Spread of tau pathology in a mouse model of AD assessed by MRI is associated with reduced brain tissue volume but not neuron loss. Tau pathology in Alzheimer’s disease (AD) first develops in the entorhinal cortex (EC), then spreads to the hippocampus, followed by the neocortex. Overall, tau pathology correlates well with neurodegeneration and cell loss, but the spatial and temporal association between tau pathology and overt volume loss (atrophy) associated with structural changes or cell loss is unclear. Using in vivo magnetic resonance imaging (MRI) with tensor-based morphometry (TBM), we mapped the spatiotemporal pattern of structural changes in a mouse model of AD-like progressive tauopathy. A novel, coregistered in vivo MRI atlas was then applied to identify regions in the medial temporal lobe that had a significant volume reduction. Our study shows that in a mouse model of tauopathy spread, the propagation of tau pathology from the EC to the hippocampus is associated with TBM-related atrophy, but atrophy in the dentate gyrus and subiculum precedes overt cell loss.
The Mechanism of Vesicle Solubilization by the Detergent Sodium Dodecyl Sulfate

Membrane solubilization by sodium dodecyl sulfate (SDS) is indispensable for many established biotech-nological applications, including viral inactivation and protein extraction. Although the ensemble thermo-dynamics have been thoroughly explored, the underlying molecular dynamics have remained inaccessible, owing to major limitations of traditional measurement tools. Here, we integrate multiple advanced biophysical approaches to gain multi-angle insight into the time-dependence and fundamental kinetic steps associated with the solubilization of single sub-micron sized vesicles in response to SDS. We find that the accumulation of SDS molecules on in-tact vesicles triggers biphasic solubilization kinetics comprising an initial vesicle expansion event followed by rapid lipid loss and micellization. Our findings support a general mechanism of detergent-induced membrane solubilization and we expect the framework of correlative biophysical technologies presented here will form a general platform for elucidating the complex kinetics of membrane perturbation induced by a wide variety of surfactants and disrupting agents.
Epigenetic Consequences of Hormonal Interactions between Opposite-sex Twin Fetuses

In human opposite-sex twins, certain phenotypic traits of the female are affected negatively by testosterone transfer from the male, while the male may or may not be affected by the female in utero. However, no study was carried out to uncover the epigenetic basis of these effects. Here, we generated DNA methylation data from 54 newborn twins and histone modification data from 14 newborn twins, including female-female (FF), female-male (FM), and male-male (MM) newborn twins, to exclude the effects of postnatal environment and socialization, and investigated the epigenetic consequences of prenatal interactions between female and male gonadal hormones. We found that FM-Fs (female in FM twins) were distinguishable from FF twins by their DNA methylome, as were FM-Ms (male in FM twins) from MM twins. The correlation between genome-wide DNA methylation of females and males showed that FM-Fs, but not FFs, were closer to males from FM-Ms and MMs. Interestingly, the DNA methylomic differences between FM-Fs and FFs, but not those between FM-Ms and MMs, were linked to cognition and the nervous system. Meanwhile, FM-Ms and MMs, but not FM-Fs and FFs, displayed differential histone modification of H3K4me3, which were linked to immune responses. These findings provide epigenetic evidence for the twin testosterone transfer hypothesis and explain how prenatal hormone exposure is linked to reported and novel traits of childhood and adult through the epigenome in opposite-sex twins. Author Summary Prenatal exposure to testosterone may affect physiological, cognitive, and behavioral traits in females with male co-twins, while the males in opposite-sex twins present weak and inconsistent influences. In this study, we systematically investigated the hormonal interactions between opposite-sex twins in newborns from epigenetics including DNA methylation and histone modifications. We show that DNA methylome in FM-Fs (female in FM twins) was different from FF twins and their DNA methylomic differences were associated with cognition and the nervous system. We also suggest that FM-Ms (male in FM twins) were distinguishable from MM twins by their DNA methylome and FM-Ms versus MMs displayed differential histone modification of H3K4me3, which were linked to immune responses. Our study provides insight into the epigenetic explanation for hormonal influences between opposite-sex fetuses.
The framework of lncRNAs and genes at early pollen developmental stage in a PTGMS wheat line

Wheat photo-thermosensitive genic male sterile (PTGMS) line is a vital material in the two-line hybrid wheat breeding system in which functional pollen production is highly associated with temperature during early developmental stage. Understanding the potential mechanism of pollen infertility induced by low temperature in PTGMS wheat is crucial for the effective utilization of genetic resources to guide wheat breeding. Herein, we combined full-length single-molecular sequencing and Illumina short reads sequencing data to obtain the high-resolution spatio-temporal transcriptome map of pollen under low temperature stress at mother cell, dyad and tetrad stages in PTGMS line BS366. Cytological descriptions and whole transcriptome analysis revealed a global landscape of low temperature altered pollen fertility transformation via regulating the transcriptional patterns of cytoskeleton-related lncRNAs and their target genes, which involved in the calcium signaling and vesicle trafficking pathways on cytoskeleton homeostasis at different stages of meiosis. Overall, our results provided the transcriptional and cytological evidences for understanding the low temperature-induced pollen sterility deficiency in PTGMS wheat line.
A new method for distinguishing human and mouse cells in situ

The mouse xenograft model is one of the most widely used animal model for biomedicine research. It is vital to distinguish the cells from different species, especially for the spatial distribution information. However, the available strategies of species-specific detection are either inapplicable in situ or of low specificity. Here, we reported a method based on DAPI staining, which offers an effective, convenient way that accurately identifies human and mouse nuclei at single-cell level in situ. This method was proven to be effective in cell co-culture and tumor xenograft tissue section. Microscopic imaging results shows obvious DAPI plaques-like structures in mouse nuclei, but absent in human nuclei. Moreover, we found these structures are co-localized with mouse major satellite DNA, which is located pericentromere in mouse, but absent in human. Our study provides a high-performance method that can be widely used for distinguish human and mouse cell in situ.