Miracle-dz/UniFAR-FTUs huggingface dataset:
flexLiTE: flexible micro-LED integrated optoelectrodes for minimally-invasive chronic deep-brain study

Understanding complex neuronal circuitry and its functions of a living organism requires a specialized tool which is capable of (i) recording a large ensemble of neuronal signals at single cell resolution, (ii) modulating neuronal activities optogenetically at the same time, and (iii) sustaining functionality for long-term chronic experiments without significant tissue degeneration or device migration. We hereby present an ultra-flexible, minimally-invasive, Michigan-type neural probe for chronic opto-electrophysiology studies: flexLiTE (flexible micro-LED integrated optoelectrodes). flexLiTE incorporates monolithically integrated, soma-sized micro-inorganic LEDs (μILEDs, 12 individually operated) and 32 recording electrodes. The stimulation and recording modalities are integrated by stacking two modules on a flexible shank, resulting in a 115 μm-wide,12 μm-thick, 10 mm-long optoelectrode. From prototype devices, we demonstrated the reliable operation of flexLiTEs for recording and modulation of hippocampal neurons in a freely moving mouse for over ~2 month.
Reionization during hierarchical clustering in a universe dominated by cold dark matter

We investigate reheating of the universe by early formation of stars and quasars in the hierarchical clustering scheme of cold dark matter scenario, with perturbation fluctuations normalized by the COBE data. It is found that ionizing uv flux from OB stars with the abundance given by the standard initial mass function is strong enough to ionize the universe from $z\approx 30$ to the present epoch, if 1--2\% of the collapsed baryons go into stars. This lessens significantly the CMB anisotropies at a small angular scale. Reionization also increases the Jeans mass to $M_{\rm luminous}\approx 10^9M_\odot$ for $z\lsim 10$, which leads to a cut-off of the luminosity function of normal galaxies on a faint side. A strong uv flux is expected at $z\approx 2-5$, and the null result of the Gunn-Peterson test is naturally explained. Early star formation also results in production of heavy elements, and the observational metal abundance sets a strong constraint on the photon energy injection into the intergalactic space.
ATG5- and ATG7-mediated autophagy regulates pollen tube guidance and male fertility in Arabidopsis thaliana

Autophagy functions as a crucial cellular scavenger by targeting cytoplasmic cargo to specific lysosome/vacuole for degradation. Autophagy-related (ATG) core proteins including ATG5 and ATG7 are evolutionarily conserved factors that are spatiotemporally orchestrated to regulate multiple processes of autophagy in yeast, mammalian and plant cells. However, autophagy is believed to be functionally dispensable in Arabidopsis thaliana since severe defects during plant growth, development and reproduction have not been observed in most of the ATG loss-of-function mutants, including atg5 and atg7, under standard cultivation conditions. In this study, we report that autophagy does in fact play roles in regulating pollen tube growth guidance and male fertility in Arabidopsis thaliana. A detailed re-assessment of atg5 and atg7 mutants revealed greatly reduced autophagy activity in germinated pollens and the seed formation within siliques is partially abolished. Next, we demonstrated that both the pollen germination ratio and pollen tube length of the mutants decreased at the beginning of germination by time-lapse tracking of pollen germination in vitro and in vivo. Additionally, we observed occurrences of pollen tube twisting and stacking during their growth towards the ovules. Finally, we found abnormal pollen grains containing only a single sperm cell or an undivided generative nucleus. Collectively, these results indicate that ATG5- and ATG7-mediated autophagy is functionally involved in regulating pollen germination, tube growth guidance and sperm cell development in Arabidopsis thaliana.
Implementation of the β-hydroxyaspartate cycle increases growth performance of Pseudomonas putida on the PET monomer ethylene glycol

Ethylene glycol (EG) is a promising next generation feedstock for bioprocesses. It is a key component of the ubiquitous plastic polyethylene terephthalate (PET) and other polyester fibers and plastics, used in antifreeze formulations, and can also be generated by electrochemical conversion of syngas, which makes EG a key compound in a circular bioeconomy. The majority of biotechnologically relevant bacteria assimilate EG via the glycerate pathway, a wasteful metabolic route that releases CO2 and requires reducing equivalents as well as ATP. In contrast, the recently characterized β-hydroxyaspartate cycle (BHAC) provides a more efficient, carbon-conserving route for C2 assimilation. Here we aimed at overcoming the natural limitations of EG metabolism in the industrially relevant strain Pseudomonas putida KT2440 by replacing the native glycerate pathway with the BHAC. We first prototyped the core reaction sequence of the BHAC in Escherichia coli before establishing the complete four-enzyme BHAC in Pseudomonas putida. Directed evolution on EG resulted in an improved strain that exhibits 35% faster growth and 20% increased biomass yield compared to a recently reported P. putida strain that was evolved to grow on EG via the glycerate pathway. Genome sequencing and proteomics highlight plastic adaptations of the genetic and metabolic networks in response to the introduction of the BHAC into P. putida and identify key mutations for its further integration during evolution. Taken together, our study shows that the BHAC can be utilized as ‘plug-and-play’ module for the metabolic engineering of two important microbial platform organisms, paving the way for multiple applications for a more efficient and carbon-conserving upcycling of EG in the future.
Pacsin 2-dependent N-cadherin internalization regulates the migration behaviour of malignant cancer cells

Cell migration is essential for both physiological and pathological processes such as embryonic morphogenesis, wound repair and metastasis of cancer cells. Collective cell migration is the coordinated movement of multiple cells connected with cadherin-based adherence junctions. Cadherins undergo dynamic intracellular trafficking and their surface level is determined by a balance between endocytosis, recycling and degradation. However, regulatory mechanisms of cadherin turnover in the collective cell migration remain to be elucidated. In this study, we show that a BAR domain protein pacsin 2 plays an essential role in collective cell migration by regulating the internalization of N-cadherin in human bladder cancer cells T24. Pacsin 2 and its associating GTPase dynamin 2 colocalized with N-cadherin at the cell periphery in T24 cells. Depletion of either pacsin 2 or dynamin 2 induced interdigitating cell-cell contacts enriched with N-cadherin. Imaging analyses of the wound healing assay showed that pacsin 2-depleted T24 cells migrated in a collective and directed manner in contrast with randomly migrating control cells. Furthermore, cell-surface biotinylation assay showed that internalization of N-cadherin is attenuated in pacsin 2-depleted cells. Interestingly, the GST-pulldown assay demonstrated that the SH3 domain of pacsin 2 binds to the cytoplasmic domain of N-cadherin, suggesting that surface levels of N-cadherin are regulated by pacsin 2-mediated endocytosis. These data support new insights into a novel endocytic route of N-cadherin in collective cell migration providing pacsin 2 as a possible therapeutic target for cancer metastasis.
A complex role of Arabidopsis CDKD;3 in meiotic progression and cytokinesis

Meiosis is a specialized cell division that halves the number of chromosomes in two consecutive rounds of chromosome segregation. In angiosperm plants is meiosis followed by mitotic divisions to form rudimentary haploid gametophytes. In Arabidopsis, termination of meiosis and transition to gametophytic development is governed by TDM1 and SMG7 that mediate inhibition of translation. Mutants deficient in this mechanism do not form tetrads, but instead undergo multiple cycles of aberrant nuclear divisions, that are likely caused by the failure to downregulate cyclin dependent kinases during meiotic exit. A suppressor screen to identify genes that contribute to meiotic exit uncovered a mutation in CDKD;3 that alleviates meiotic defects in smg7 deficient plants. The CDKD;3 deficiency prevents aberrant meiotic divisions observed in smg7 mutants, or delays their onset after initiation of cytokinesis, which permits formation of functional microspores. Although CDKD;3 acts as an activator of CDKA;1, the main cyclin dependent kinase that regulates meiosis, cdkd;3 mutation appears to promote meiotic exit independently of CDKA;1. Furthermore, analysis of CDKD;3 interactome revealed enrichment for proteins implicated in cytokinesis suggesting a more complex function of CDKD;3 in cell cycle regulation.
Genetic drivers of chromosomal integron stability

The integron is a bacterial recombination system that allows acquisition, stockpiling and expression of promoterless genes embedded in cassettes. Some integrons, like the one found in the second chromosome of Vibrio cholerae , can be particularly massive and contain hundreds of non-expressed cassettes. It is unclear how such genetic structures can be stabilized in bacterial genomes. Here, we reveal that the orientation of integrons toward replication within bacterial chromosomes is essential to their stability. Indeed, we show that upon inversion of the V. cholerae chromosomal integron, its plasticity is dramatically increased. This correlates with a strong growth defect which we show is mostly due to the excision of a particular type of cassettes bearing their own promoter and encoding toxin-antitoxin systems. This so called “abortive excision” of toxin-antitoxin systems can prevent the inversion of chromosomal integrons and the associated extensive loss of cassettes. Our analysis of the available sedentary chromosomal integrons in genome database show a robust correlation between the size of the cassette array and the number of toxin-antitoxin cassettes. This study thus provides a striking example of the relationship between genome organization, genome stability, and an emerging property of toxin-antitoxin systems.
Patterns of numtogenesis in sixteen different mice strains

Numtogenesis is the phenomenon of mitochondrial sequence localisation and integration into the nuclear genome. This is an ongoing process which contributed to the complexity of eukaryotic genomes. The sequences that are integrated into the nuclear genome are called nuclear mitochondrial sequences (numt). numts have a wide variety of applications in tumor biology, phylogenetic studies, forensic research and so on. Mus musculus musculus is the most popular model organism. Numerous mouse strains are used in medical research to model human diseases. numts were described in the genome of Mus musculus musculus just like in many other species however the characterisation of numts in different mouse strains is missing. In this study we explored the patterns of numtogenesis in 16 mouse strains by aligning the nuclear genomes with the corresponding mitochondria. Investigation of numts shed light on strain specific differences and resembles the phylogenetic relationships as to our current knowledge in most of the cases.
MOSQUITO MICROBIOMES OF RWANDA: CHARACTERIZING MOSQUITO HOST AND MICROBIAL COMMUNITIES IN THE LAND OF A THOUSAND HILLS

Mosquitoes are a complex nuisance around the world, and tropical countries bear the greatest brunt of the burden of mosquito-borne diseases. Rwanda has had success in reducing malaria and some arboviral diseases over the last few years, but still faces challenges to elimination. By building our understanding of in situ mosquito communities in Rwanda at a disturbed, human-occupied site and at a natural, preserved site, we can build our understanding of natural mosquito microbiomes toward the goal of implementing novel microbial control methods. Here, we examined the composition of collected mosquitoes and their microbiomes at two diverse sites using Cytochrome c Oxidase I sequencing and 16S V4 barcode sequencing. The majority of mosquitoes captured and characterized in this study are the first-known record of their species for Rwanda but have been characterized in other nations in East Africa. Beta diversity metrics were significantly different between sampling sites, mosquito genera, and mosquito species, but not between mosquito sexes, catch method, or presumed bloodfed status. Bacteria of interest for arbovirus control, Asaia, Serratia, and Wolbachia, were found in abundance at both sites, but were more prevalent at the disturbed site and varied greatly by species. Additional studies to build our understanding of naturally-formed microbial communities are essential to safely employing microbial control methods and further reducing the burden of mosquito-borne diseases.
Esearch3D: propagating gene expression in chromatin networks to illuminate active enhancers

Most cell type-specific genes are regulated by the interaction of enhancers with their promoters. The identification of enhancers is not trivial as enhancers are diverse in their characteristics and dynamic in their interaction partners. Currently, enhancer-associated features such as histone modifications, co-activators or bi-directional transcription are used in lieu of any definitive and universal enhancer feature. We present Esearch3D, a new approach that leverages network theory approaches to identify active enhancers. Our work is based on the fact that enhancers act as a source of regulatory information to increase the rate of transcription of their target genes and that the flow of this information is mediated by the folding of chromatin in the three-dimensional (3D) nuclear space between the enhancer and the target gene promoter. Esearch3D reverse engineers this flow of information to calculate the likelihood of enhancer activity in intergenic regions by propagating the transcription levels of genes across 3D-genome networks. Regions predicted to have high enhancer activity are shown to be enriched in annotations indicative of enhancer activity. These include: enhancer-associated histone marks, bi-directional CAGE-seq, STARR-seq, P300 and RNA polymerase II ChIP-seq, and expression quantitative trait loci (eQTL). Esearch3D successfully leverages the relationship between chromatin architecture and global transcription and represents a novel approach to predict active enhancers and understand the complex underpinnings of regulatory networks. The method is available at: https://github.com/InfOmics/Esearch3D.
Bachelor Thesis Mediainformatics ENSO impact on river discharge in South America

The impact of the El Ni˜no Southern Oscillation on hydrological systems such as rivers is well known, but most existing studies are severely limited by data coverage. Time series of gauging stations fade in and out over time, which makes hydrological large scale and long time analysis challenging. Especially when investigating rarely occurring extreme events missing data is either con-straining the spatial area or the timespan of the study. A data driven analysis of the ENSO impact on river discharge in South America is therefore missing. The purpose of this study is to overcome this spatio-temporal trade-oﬀ and ﬁll the gap of such an assessment using in situ data. We use Gaussian Process Regression to infer missing streamﬂow data based on temporal correlations of stations with missing values to others with data. By using 216 stations, from the ”Global Streamﬂow Indices and Metadata Archive”, that initially cover the 56 year timespan, we were able to extend the data by over 11-fold as we could estimate missing data for 2210 stations. The spatial impact of strong ENSO events between 1960 and 2016 has then been analysed with the extended dataset. For both La Ni˜na and El Ni˜no events the area of their spatial impact was much larger than its impact on climate would suggest. Eastern Paciﬁc El Ni˜nos had an exceptionally strong impact, like the strong event of 1982/83, which was by far the most intense event in our study. The top-level maps reveal that strong ENSO events are capable of impacting peak river discharge and ﬂoods over the whole continent whereas the individual impact maps show very diﬀerent characteristics and severity in its impact pattern.
The Signature of Lithospheric Anisotropy at Post‐Subduction Continental Margins: New Insight From XKS Splitting Analysis in Northern Borneo

The relative paucity of recent post‐subduction environments globally has meant that, so far, little is known about tectonic processes that occur during and after subduction termination, as previously convergent tectonic plates adjust to the new stress regime. The region of Southeast Asia that now encompasses northern Borneo has been host to two sequential episodes of subduction—both now terminated—since the mid‐Paleogene. It is expected that these processes will have left signatures in the fabric of the upper mantle, which are manifest in the form of seismic anisotropy. We investigate the evidence for, and alignment of, anisotropic fabrics by measuring the splitting of a family of teleseismic shear phases. These observations provide a measure of the orientation of the effective anisotropic elastic tensor, in the form of the orientation of the fast shear‐wave polarization, ϕ, and add constraints on the strength of the anisotropic fabric, in the form of the delay time, δt. We observe two principal trends across northern Borneo that appear to be confined to the lithosphere. These patterns are likely related to tectonic processes associated with subduction, continental collision, and oceanic basin formation, events that can exert primary influence on the formation of post‐subduction settings.
Note on the order of successive displacements

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Die Werte der Franz-Reidemeister-Torsion bei torsionsberandenden Mannigfaltigkeiten.

Ist f r eine rc-dimensionale unberandete Mannigfaltigkeit) M" eine Franz-Reidemeister-Torsion erkl rt, so folgt aus der Existenz dualer Zellzerlegungen im Homotopiekettenring nach Franz [3] f r die Torsionswerte: Δ (Μ) · Δ(Μ)~ ~ 1; dabei entsteht die Konjugation durch den bergang χ -> x~ in π^Μ). F r berandete Mannigfaltigkeiten M mit Rand dM hat Milnor in [7] eine analoge Beziehung angegeben: aus der Existenz von Δ (M) folgt diejenige von Δ(3Μ), und es gilt
IRRITABLE BOWLE SYNDROME: SIMPLE SIGN DEEP PROBLEM

: Irritable bowel syndrome (IBS), referred to previously as spastic or nervous colon, and spastic bowel, is a functional gastrointestinal disorder characterized by a group of symptoms accompanied together that include abdominal pain and changes in the consistency of bowel movements. These symptoms occur over a long time, often years. It has been classified into four main types depending on whether diarrhea is common, constipation is common, both are common (mixed/alternating), or neither occurs very often (IBS-D, IBS-C, IBS-M/IBS-A, or IBS-U, respectively). IBS negatively affects quality of life and may result in missed school or work. Disorders such as anxiety, major depression, and chronic fatigue syndrome are common among people with IBS. IBS does not lead to malabsorption. The causes of IBS are not clear. Theories include combinations of gut–brain axis problems, gut motility disorders, pain sensitivity, infections including small intestinal bacterial overgrowth, neurotransmitters, genetic factors, and food sensitivity. Onset may be triggered by an intestinal infection or stressful life event. Diagnosis based on symptoms in the absence of worrisome features and once other potential conditions have been ruled out. Worrisome features include onset at greater than 50 years of age, weight loss, blood in the stool, or a family history of inflammatory bowel disease. Other conditions that may present similarly include celiac disease, microscopic colitis, inflammatory bowel disease, bile acid malabsorption, and colon cancer. There is no known cure for IBS. Treatment is carried out to improve symptoms, this may include dietary changes, medication, taking human milk oligosaccharides, probiotics, and counseling. Dietary measures include increasing soluble fiber intake, a gluten-free diet, or a short-term diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs). The medication loperamide may be used to help with diarrhea while laxatives may be used to help with constipation. Antidepressants may improve overall symptoms and reduce pain. Patient education and a good doctor–patient relationship are an important part of care.
Interactive Stratospheric Aerosol models response to different amount and altitude of SO 2 injections during the 1991 Pinatubo eruption

Recent model inter-comparison studies highlighted model discrepancies in reproducing the climatic impacts of large explosive volcanic eruptions, calling into question the reliability of global aerosol model simulations for future scenarios. Here, we analyse the simulated evolution of the stratospheric aerosol plume following the well observed June 1991 Mt. Pinatubo eruption by six interactive stratospheric aerosol microphysics models in comparison to a range of observational data sets. Our primary focus is on the uncertainties regarding initial SO 2 emission following the Pinatubo eruption in 1991, as pre- 5 scribed in the Historical Eruptions SO 2 Emission Assessment experiments (HErSEA), in the framework of the Interactive Stratospheric Aerosol Model Intercomparison Project (ISA-MIP). Six global models with interactive aerosol microphysics took part in this study: ECHAM6-SALSA, EMAC, ECHAM5-HAM, SOCOL-AERv2, ULAQ-CCM and UM-UKCA. Model simulations are performed by varying SO 2 injection amount (ranging between 5 and 10 Tg-S), and the altitude of injection (between 18-25 km). sets of initial parameters for the stratospheric SO 2 , both in terms of magnitude (5, 7 or 10 Tg-S injected) and altitude of the SO 2 plume (18-20, 21-23, 18-23 km, uniformly distributed). We found that different sets of initial conditions of the volcanic emissions are required in different models to reproduce available observations from that time period. The experiment protocol that best ﬁts the observation also changes in some models depending on the variables to be considered (aerosol optical depth, effective radius, sulfate burden, surface area density).