Miracle-dz/UniFAR-FTUs huggingface dataset:
Graph combinatorics based group-level network inference for brain connectome analysis

We consider group-level statistical inference for networks, where outcomes are multivariate edge variables constrained in an adjacency matrix. The graph notation is used to represent the network outcome variables, where nodes are identical biological units (e.g. brain regions) shared across subjects and edge-variables indicate the strengths of the interactive relationships between nodes. The edge-variables vary across subjects and may be associated with covariates of interest. The statistical inference for multivariate edge-variables is challenging because both localized inference on individual edges and the joint inference of a combinatorial of edges (network-level) are desired. We develop a group-level network inference model to integrate graph theory and combinatorics into group-level network statistical inference. We first propose an objective function with ℓ0 norm regularization to capture latent subgraphs/subnetworks accurately by suppressing false positive edges. We next statistically test each detected subnetwork using graph combinatorics based statistical inferential procedure. We apply the proposed approach to a brain connectome study to identify latent brain functional subnetworks that are associated with brain disorders and verify the findings using an independent replicate data set. The results demonstrate the proposed method outperform existing multivariate statistical methods by simultaneously reducing false positive and false negative discovery rates and increasing replicability.
Birds of a feather: Hearing and potential noise impacts in puffins (Fratercula arctica)

Seabirds are perhaps the most imperiled group of birds. They can readily transit between air and water and enact key behaviors in both habitats. With this amphibious lifestyle, they likely face unique auditory constraints in air, underwater, and even subterranean. Unfortunately, like many other birds, anthropogenic noise seems to be a stressor, yet we have few data on seabird hearing abilities and noise impacts. Here we examined the hearing in the Atlantic puffin, Fratercula arctica . Hearing tests were conducted in-air in a portable semi-anechoic crate using physiological, auditory evoked potential (AEP) methods with temporarily wild-caught, sedated birds. Hearing data were quite clear and provided an auditory curve that was not unlike AEP hearing thresholds in other birds. Lowest measured thresholds were found at 1-2 kHz with a gradual increase in AEP-thresholds at lower frequencies and a steeper increase at higher frequencies. Responses were measurable from 0.5 to 6 kHz. Obtaining auditory data for seabirds is particularly valuable considering their conservation status, population-level declines, and a minimal understanding of how they may use or be influenced by their acoustic habitat. These data show sensitive in-air hearing, and supports concerns about coastal noise which could have clear ecologically relevant consequences.Seabirds are perhaps the most imperiled group of birds. They can readily transit between air and water and enact key behaviors in both habitats. With this amphibious lifestyle, they likely face unique auditory constraints in air, underwater, and even subterranean. Unfortunately, like many other birds, anthropogenic noise seems to be a stressor, yet we have few data on seabird hearing abilities and noise impacts. Here we examined the hearing in the Atlantic puffin, Fratercula arctica . Hearing tests were conducted in-air in a portable semi-anechoic crate using physiological, auditory evoked potential (AEP) methods with temporarily wild-caught, sedated birds. Hearing data were quite clear and provided an auditory curve that was not unlike AEP hearing thresholds in other birds. Lowest measured thresholds were found at 1-2 kHz with a gradual increase in AEP-thresholds at lower frequencies and a steeper increase at higher frequencies. Responses were measurable from 0.5 to 6 kHz. Obtaining auditory data for sea.
Genome-wide association analysis of 95 549 individuals identifies novel loci and genes influencing optic disc morphology.

Optic nerve head morphology is affected by several retinal diseases. We measured the vertical optic disc diameter (DD) of the UK Biobank (UKBB) cohort (N = 67 040) and performed the largest genome-wide association study (GWAS) of DD to date. We identified 81 loci (66 novel) for vertical DD. We then replicated the novel loci in International Glaucoma Genetic Consortium (IGGC, N = 22 504) and European Prospective Investigation into Cancer-Norfolk (N = 6005); in general the concordance in effect sizes was very high (correlation in effect size estimates 0.90): 44 of the 66 novel loci were significant at P < 0.05, with 19 remaining significant after Bonferroni correction. We identified another 26 novel loci in the meta-analysis of UKBB and IGGC data. Gene-based analyses identified an additional 57 genes. Human ocular tissue gene expression analysis showed that most of the identified genes are enriched in optic nerve head tissue. Some of the identified loci exhibited pleiotropic effects with vertical cup-to-disc ratio, intraocular pressure, glaucoma and myopia. These results can enhance our understanding of the genetics of optic disc morphology and shed light on the genetic findings for other ophthalmic disorders such as glaucoma and other optic nerve diseases.
The effect of ATP-binding cassette (ABC) transporters in human cancers

Multi-drug resistance (MDR) can be defined as a negative effect on the drug-target relationships, decreasing in intracellular drug aggregation. ABC (ATP-binding cassette) are popular transporter proteins in the development of MDR. ABC proteins in the cell membrane structure reduce the therapeutic efficacy and cause drug resistance in cancer patients. Resistance to chemotherapy is a remarkable and important issue in the treatment of cancer patients. These drug resistance proteins interfere with the drugs administered to patients, resulting in a decrease in bioavailability of these drugs and a reduction in their passage through the blood-brain barrier. ABC transporters are the largest family of transmembrane proteins with 8 subfamilies assigned from A to G based on sequence and structural homology. In this review, general information about ABC proteins is mentioned and the role of ABC proteins causing MDR in cancers is also discussed.
Molecular phylogeny of the large South American genus
 Eriosyce
 (Notocacteae, Cactaceae): Generic delimitation and proposed changes in infrageneric and species ranks

Eriosyce is one of most species‐rich genera within Notocacteae (Cactaceae) harboring a variety of stem and flower morphologies, and fruits with basal abscission. The lack of a well‐sampled molecular phylogeny contributes to the current taxonomic instability of the genus, where its circumscription and infrageneric classification has been questioned. Specimens of Eriosyce (63 taxa) plus 19 outgroups were analyzed through sequencing three plastid noncoding introns (rpl32‐trnL, trnL‐trnF, trnH‐psbA), one plastid gene (ycf1), and one nuclear gene (PHYC). Individual markers and concatenated matrices were analyzed using maximum likelihood and Bayesian approaches. Phylogenetic analyses strongly support the monophyly of Eriosyce s.l. Furthermore, seven clades within Eriosyce s.l. were defined based on supported branches, although one of them was weakly supported. Our results suggest that some past taxonomic proposals have low phylogenetic support and should no longer be used, e.g., based on their scattered positions in the phylogenetic reconstruction, several infraspecific taxa appear unrelated to the typical form of the species in which they had been placed. We present a phylogeny‐informed infrageneric classification of the genus Eriosyce, and new combinations are proposed to update the nomenclature of species and sections.
Mutation of the ALBOSTRIANS Ohnologous Gene HvCMF3 Impairs Chloroplast Development and Thylakoid Architecture in Barley due to Reduced Plastid Translation

Gene pairs resulting from whole genome duplication (WGD), so-called ohnologous genes, are retained only if at least one gene of the pair undergoes neo- or subfunctionalization. Sequence-based phylogenetic analyses of the ohnologous genes ALBOSTRIANS (HvAST/HvCMF7) and ALBOSTRIANS-LIKE (HvASL/HvCMF3) of barley (Hordeum vulgare) revealed that they belong to a newly identified subfamily of genes encoding CCT domain proteins with putative N-terminal chloroplast transit peptides. Recently, we showed that HvCMF7 is needed for chloroplast ribosome biogenesis. Here we demonstrate that mutations in HvCMF3 lead to seedlings delayed in development. They exhibit a xantha phenotype and successively develop pale green leaves. Compared to the wild type, plastids of the mutant seedlings show decreased PSII efficiency and lower amounts of ribosomal RNAs; they contain less thylakoids and grana with a higher number of more loosely stacked thylakoid membranes. Site-directed mutagenesis of HvCMF3 identified a previously unknown functional region, which is highly conserved within this subfamily of CCT domain containing proteins. HvCMF3:GFP fusion constructs localized to plastids. Hvcmf3Hvcmf7 double mutants indicated epistatic activity of HvCMF7 over HvCMF3. The chloroplast ribosome deficiency is discussed as the primary defect of the Hvcmf3 mutants. Our data suggests that HvCMF3 and HvCMF7 have similar but not identical functions. One-sentence summary Phylogenetic and mutant analyses of the barley protein HvCMF3 (ALBOSTRIANS-LIKE) identified, in higher plants, a subfamily of CCT domain proteins with essential function in chloroplast development.
Noninvasive DNA sampling and camera trapping suggest dramatic regional conservation status of an understudied carnivore: the Rüppell’s fox in Tunisia

ABSTRACT Rüppell’s fox, Vulpes rueppellii, is one of the four fox species occurring in North Africa. Its population status and ecology remains largely unknown. Here, we collected occurrence data from camera trapping and scat-collection based mitochondrial control region sequencing to assess the distribution range and status of the species across potential habitats in Tunisia. The collection and analysis of 342 scat samples resulted in 234 sequences of the mitochondrial control region. Our results did not reveal any evidence of Rüppell’s fox presence in Tunisia. In contrast, three other mesocarnivores were commonly recorded by camera trapping and molecular data, namely African wolf ‘Canis lupaster’, red fox ‘Vulpes vulpes’ and fennec fox ‘V. zerda’. The three species exhibited distinct geographical affinities, which are reflected in different habitat selection patterns. To the best of our knowledge, this is the first study focusing on the distribution of V. rueppellii in North Africa using both camera trapping and noninvasive genetic methods. In terms of conservation, it seems urgent to characterise the status of this species in North Africa, and particularly in Tunisia.
Investigation of the pathophysiology of progression in multiple sclerosis: studies on cerebrospinal fluid biomarkers

Investigation of the pathophysiology of progression in multiple sclerosis – Studies on cerebrospinal fluid biomarkers We work in the dark – we do what we can – we give what we have. Our doubt is our passion and our passion is our task. The rest is the madness of art. Abstract Multiple Sclerosis (MS) is considered an autoimmune disease of the central nervous system (CNS). It usually starts with a relapsing remitting (RR) course that eventually transforms into progressive (P)MS, showing neurodegenerative features. The pathogenesis behind the transition from RRMS to PMS is essentially unknown. The aim of this thesis was to investigate if biomarkers in the cerebrospinal fluid (CSF) of MS patients could provide new insights into the pathophysiology of MS progression, and if biomarker levels could reflect disease activity, disability progression , or therapeutic efficacy. Three study designs were established. The first was cross sectional and comprised MS patients, healthy controls (HC) and control subjects with another inflammato-ry disease. The second used a long-term follow-up setting in which RRMS, PMS and HC were assessed twice 8-10 years apart. The third used immunomodulatory or immunosuppressive intervention (natalizumab, mitoxantrone or rituximab) and assessed MS patients pre-and 12-24 months post-treatment. CSF biomarkers were analyzed for i) axonal damage (neurofilament light, NFL), ii) astrogliosis (glial fibrillary acidic protein, GFAP), iii) amyloid precursor protein metabolism (BACE1 activity, and sAPP/Aβ metabolites) iv) B-cell regulation (CXCL13) and v) intrathe-cal IgG synthesis (IgG index, oligoclonal IgG bands (OCB)). Increased mean GFAP levels were found in all courses of MS with the highest levels in PMS, whereas the mean NFL level of this MS population was not different from that of HC (Paper I). At long-term follow-up GFAP levels correlated with disability and had prognostic value. In contrast, increased NFL levels were found in another MS population compared to HC (Paper IV). This discrepancy might be explained by differences in disease activities between the investigated populations and due to improved sensitivity of the NFL immunoassay. We found signs of downregula-tion of BACE1 activity (Paper II) and sAPP/Aβ metabolism (Paper III) in MS. The levels of sAPP/Aβ in MS were generally decreased compared to HC suggestive of impaired neuronal function in MS. Mass spectrometry studies indicated that the sAPP/Aβ metabolism was changed in PMS compared to HC by formation of other decomposition products. We demonstrated, in opposite to the general view, changed number and pattern of OCB in …
Microtubules deform the nucleus and force chromatin reorganization during early differentiation of human hematopoietic stem cells

Hematopoietic stem cells (HSC) can differentiate into all hematopoietic lineages to support hematopoiesis. Cells from the myeloid and lymphoid lineages fulfill distinct functions with specific shapes and intra-cellular architectures. The role of cytokines in the regulation of HSC differentiation has been intensively studied but our understanding of the potential contribution of inner cell architecture is relatively poor. Here we show that large invaginations are generated by microtubule constraints on the swelling nucleus of human HSCs during early commitment toward the myeloid lineage. These invaginations are associated with chromatin reorganization, local loss of H3K9 trimethylation and changes in expression of specific hematopoietic genes. This establishes the role of microtubules in defining the unique lobulated nuclear shape observed in myeloid progenitor cells and suggests that this shape is important to establish the gene expression profile specific to this hematopoietic lineage. It opens new perspectives on the implications of microtubule-generated forces, in the early specification of the myeloid lineage.
Dimensionality changes actin network through lamin A and C and zyxin

The actin cytoskeleton plays a key role in differentiation of human mesenchymal stromal cells (hMSCs), but its regulation in 3D tissue engineered scaffolds remains poorly studied. hMSCs cultured on 3D electrospun scaffolds made of a stiff material do not form actin stress fibers, contrary to hMSCs on 2D films of the same material. On 3D electrospun- and 3D additive manufactured scaffolds, hMSCs also displayed fewer focal adhesions, lower lamin A and C expression and less YAP1 nuclear localization. Together, this shows that dimensionality prevents the build-up of cellular tension, even on stiff materials. Knock down of either lamin A and C or zyxin resulted in fewer stress fibers in the cell center. Zyxin knock down reduced lamin A and C expression, but not vice versa, showing that this signal chain starts from the outside of the cell. Our study demonstrates that dimensionality changes the actin cytoskeleton through lamin A and C and zyxin, an important insight for future scaffold design, as the actin network, focal adhesions and nuclear stiffness are all critical for hMSC differentiation.
Resource acquisition strategies facilitate Gilbertiodendron dewevrei monodominance in African lowland forests

Tropical forests are hyperdiverse, yet extensive areas of monodominant forest occur in the tropics worldwide. Most long‐lived and persistent monodominant tree species form ectomycorrhizal fungi symbioses, allowing them to obtain nutrients directly from soil organic matter. This might promote monodominance by reducing nutrient availability to co‐occurring species, the majority of which form associations with arbuscular mycorrhizal fungi. Gilbertiodendron dewevrei forest is the most widespread monodominant forest in tropical Africa. Its distribution appears determined in part by moisture availability, but its monodominance is not thought to be driven by its fungal partner or soil fertility. Here, we compare soil fertility of 20 G. dewevrei stands to mixed forest from three sites across an 8,400 km2 region of the Central African Republic and the Republic of Congo. In contrast to previous studies, we find monodominant G. dewevrei stands associated with infertile soils, as base cations (calcium, magnesium, total exchangeable bases) and extractable manganese are extremely low, and significantly lower in soils under G. dewevrei forest compared to mixed forest. Further, and consistent with ectomycorrhizal forests globally, soil carbon to nitrogen and carbon to phosphorus ratios are significantly higher in G. dewevrei stands than in mixed forest stands, providing evidence in support of direct acquisition of nitrogen and phosphorus from soil organic matter by ectomycorrhizal fungi. Gilbertiodendron dewevrei recruits from the seedling bank, with its large seedlings surviving in high densities for over a decade. We tested whether light plasticity could facilitate monodominance by growing seedlings of G. dewevrei under controlled light conditions. We found that its seedlings grow well under a wide range of irradiance levels and conclude that this plasticity affords a competitive advantage. Synthesis. We reframe the discussion of factors contributing to monodominance of Gilbertiodendron dewevrei into one of resource acquisition and use efficiency. In particular, G. dewevrei is associated with moist and infertile soils and competes well under a variety of light conditions. Our data are consistent with a model where root associations with ectomycorrhizal fungi drive monodominance through the direct acquisition of nutrients from soil organic matter, promoting nutrient limitation of co‐occurring species.
Low air humidity during cultivation promotes stomatal closure ability in rose

In greenhouse horticulture, evaporative demand varies between seasons. For instance, plants are typically exposed to low relative air humidity (RH) during summer, whereas elevated RH prevails in winter. Since high RH during cultivation impairs stomatal functioning, some opposite changes might be expected, when plants are subjected to long-term low RH. To investigate this, Rosa hybrida ‘Pasadena’ was cultivated at 40, 60 or 90% RH. Plant performance, transpiration, stomatal closing ability and anatomy were recorded. As RH increased from 40 to 60% as well as from 60 to 90%, plants showed larger leaf area and thinner leaves. Plant water loss was mainly determined by ambient RH in the growing environment, with stomatal conductance (gs) being of secondary importance. With increasing RH, plant transpiration declined at growth environment. Larger stomata were found at 90% RH, as compared to 40 or 60%. Stomatal physiology was considerably affected by 90% RH, including reduced gs oscillations within the photoperiod, attenuated opening response following dark/light transition, as well as reduced closing response upon darkening. The plants cultivated at 90% RH had a reduced ability to control water loss upon water deprivation, compared to those grown at 60%. In contrast, cultivation at 40% RH resulted in stomata, which were much more responsive to water stress, compared to 60% RH-grown plants. This superiority was dual: lower transpiration rate combined with less severe leaf drying to induce stomatal closure. In conclusion, low RH during cultivation, which is typical during summer, leads to thicker leaves with very responsive stomata.
Regulation of infrapopulations of Cryptocotyle lingua on cod

To study the infection dynamics of metacercariae of the digenean Cryptocotyle lingua, wild living Atlantic cod, Gadus morhua, were caged for 18 months close to the shore. Here they were exposed to naturally occurring transmission stages of the parasite. First, both the abundance and the variance to mean ratio of metacercariae increased, but during the second half of the study the abundance levelled out, and the variance to mean ratio showed a significant decrease. Host mortality was negligible throughout the study. Based on the relationship between pigment spots and metacercariae observed by skin digestion, there was no indication of density-dependent parasite mortality. We conclude that the infrapopulations of metacercariae on the caged cod probably were regulated by density-dependent host responses acting against the cercariae.
Understanding and engineering the cytosolic redox balance of Saccharomyces cerevisiae during glycerol catabolism

The valorization of carbon-rich industrial waste-streams, such as crude glycerol derived from the biodiesel industry, is a promising avenue to overcome the dependence on fossil resources for the production of certain chemicals. Glycerol has a higher degree of reduction compared to sugars, allowing higher theoretical yields of small reduced molecules, when used as a substrate in industrial biotechnological processes. Several microorganisms are able to catabolize glycerol, including the Saccharomyces cerevisiae strain CBS 6412-13A. In order to utilize glycerol’s degree of reduction for S. cerevisiae-based synthesis of fermentation products, metabolic engineering is required. A replacement of the native FAD-dependent L-glycerol 3-phosphate pathway by the artificial NADH-delivering dihydroxyacetone pathway is supposed to provide glycerol-derived electrons for the cytosolic formation of fermentation products. However, S. cerevisiae has potent respiratory mechanisms, that maintain cytosolic redox balance by transferring electrons from cytosolic NADH to oxygen. During growth with e.g. ethanol or low glucose concentrations, the external NADH dehydrogenases (Nde1/2) and the L-G3P shuttle (composed of Gpd1/2 and Gut2), are contributing to cytosolic NAD+ regeneration. Their contribution with glycerol as carbon source was not investigated so far. It is demonstrated here, that in particular Nde1 significantly contributes to cytosolic redox balance in S. cerevisiae catabolizing glycerol. S. cerevisiae’s major native fermentative mechanism to oxidize NADH is alcoholic fermentation, even when oxygen is available. However, glycerol is generally considered to be a ‘non-fermentable’ carbon source for S. cerevisiae. The current work demonstrates that at least S. cerevisiae strains catabolizing glycerol via the DHA pathway are able to perform alcoholic fermentation. The results of this thesis provide important insights into the redox metabolism of S. cerevisiae catabolizing glycerol.