Miracle-dz/UniFAR-FTUs huggingface dataset:
Systems pathology analysis identifies neurodegenerative nature of age-related retinal diseases

Aging is a phenomenon associated with profound medical implications. Idiopathic epiretinal membrane (iEMR) and macular hole (MH) are the major vision-threatening vitreoretinal diseases affecting millions of aging people globally, making these conditions an important public health issue. The iERM is characterized by fibrous tissue developing on the surface of the macula, leading to biomechanical and biochemical macular damage. MH is a small breakage in the macula associated with many ocular conditions. Although several individual factors and pathways are suggested, a systems pathology level understanding of the molecular mechanisms underlying these disorders is lacking. Therefore, we performed mass spectrometry based label-free quantitative proteomics analysis of the vitreous proteomes from patients with iERM (n=26) and MH (n=21) to identify the key proteins as well as the multiple interconnected biochemical pathways contributing to the development of these diseases. We identified a total of 1014 unique proteins, of which many were linked to inflammation and complement cascade, revealing the inflammational processes in retinal diseases. Additionally, we detected a profound difference in proteomes of the iEMR and MH compared to the non-proliferative diabetic retinopathy. A large number of neuronal proteins were present at higher levels in iERM and MH vitreous, including neuronal adhesion molecules, nervous system development proteins and signalling molecules. This points toward the important role of neurodegeneration component in the pathogenesis of age-related vitreoretinal diseases. Despite of marked similarities, several unique vitreous proteins were identified in both iERM and MH conditions, providing a candidate targets for diagnostic and new therapeutic approaches. Identification of previously reported and novel proteins in human vitreous humor from patient with iERM and MH provide renewed understanding of the pathogenesis of age-related vitreoretinal diseases.
Sequence analysis of mitochondrial COII gene fragment from five Culicinae mosquito species

Sequence analysis of the mitochondrial COII gene has been used for molecular taxonomy in many insects and to reveal phylogenetic relationship among them. A ~500 to 550bp sequence of mitochondrial Cytochrome Oxidase II (COII) gene has been analyzed to construct molecular database and to establish the phylogenetic relation among the five Culicinae mosquito species (Aedes vittatus, Aedes aegypti, Culex bitaeniorhynchus, Culex vishnui and Culex quinquefasciatus) from the state of Punjab and adjoining areas (India). The sequences were found to be A+T rich and in substitution the rate of transitions was higher than the rate of transversions. Individuals of the same species grouped closely together in a Neighbor-Joining tree regardless of collection site. Conspecifics showed 2% with K2P (range = 4.1% to 15.0%).
The Mutations of Topoisomerase Genes and Their Effect on Resistance to Fluoroquinolones in Extended-Spectrum β-Lactamase-Producing Escherichia coli

Background: Fluoroquinoloneshavebeenusedforempiricaltreatmentof urinarytractinfectionsinrecentyears. Thisstudyaimed atidentifyingmutationsin gyrA and parC genesandtheircorrelationwithﬂuoroquinoloneminimalinhibitoryconcentration(MIC) among extended-spectrum β -lactamase-producing (ESBL) Escherichia coli . Methods: A total of 240 E. coli were isolated from urine of patients during 2014 and 2015 in the west of Iran. The isolates were screened for ESBL-producing phenotype using combined disc diﬀusion test. The susceptibility of ESBL isolates to ciproﬂoxacin and levoﬂoxacin was determined by disk diﬀusion and microdilution assay. PCR, sequencing and bioinformatics analysis were performed to identify mutations in gyrA and parC genes. Results: Of 240 isolates, 66 (27.5%) were ESBL positive. Of them, 45 (68.1%) isolates were resistant to both ciproﬂoxacin and levoﬂoxacin. Sequence analysis showed mutations in the quinolone resistance determining region (QRDR) in the 2 codons (Ser-83, Asp-87) of gyrA and 2 codons (Ser-80, Glu-84) of parC . One mutation at codon of Ala-192 was found outside the QRDR in parC . Conclusions: IsolateswithmutationsinQRDRof parC and gyrA hadthehigherMIClevelcomparedtoisolateswithmutationsonly in gyrA . The highest level of resistance was detected in isolates with accumulation of mutations in gyrA and parC . A high frequency of ﬂuoroquinoloneresistanceamongESBLproducing E.coli isolatesindicatedtheclusteredtransmissionof resistancegenesinthis bacterium. A new mutation outside the QRDR of parC was detected, which may play a role in ﬂuoroquinolone resistance.
Biological and evolutionary significance of cysteine-rich 'B' class pollen coat proteins (PCP-Bs) in the early stages of the Arabidopsis thaliana pollen-stigma interaction

The early stages of post-pollination in angiosperms involve multiple phases of interaction between male and female reproductive tissues. The establishment of the pollen-stigma interaction is proposed to involve a basal compatibility system that enables compatible pollen to be recognised by the receptive stigma. Divergence of components involved in this system could facilitate the establishment of prezygotic breeding barriers that would limit wasted mating opportunities, restrict interspecies gene flow and contribute to reproductive isolation. A diverse family of small secreted cysteine-rich proteins (CRPs) found in the pollen coat of members of the Brassicaceae, the pollen coat proteins (PCPs), are emerging as important regulators of the pollen-stigma interaction. One class of PCPs isolated from the pollen coat of Brassica oleracea, the PCP-Bs, have previously been described, but their function was unknown. In this study, four putative Arabidopsis thaliana PCP-B-encoding genes were identified, determined to be gametophytically expressed during the late stages of pollen development and confirmed as pollen coat proteins. Bioassays utilising single and multiple pcp-b gene knockouts revealed that AtPCP-Bs function in the early stages of post-pollination. To identify the stigmatic targets of AtPCP-B ligands, a series of protein-protein interaction (PPI) assays were carried out with heterologously expressed AtPCP-Bs and isolated stigmatic proteins. To provide insight into the evolutionary characters of PCP-Bs, phylogenetic analysis and molecular evolutionary study revealed evidence of positive selection acting on sites of genes encoding PCP-Bs and PCP-B-like proteins. Such evidence suggests that AtPCP-Bs are important components of the basal compatibility system by establishing a molecular dialogue between compatible pollen grains and the stigma. Proteomic analyses of pollen coat from Arabidopsis thaliana and Brassica oleracea uncovered large numbers of small CRPs, which may act as important regulatory factors of pollen-stigma interaction. This project shed new light on the biological and evolutionary significance of pollen coat CRPs in plant reproductive signalling.
Modeling of Craniofacial Anatomy, Variation, and Growth

s and Papers not Included in the Thesis [194] Signe S. Thorup, Tron A. Darvann, Nuno V. Hermann, Hildur Ólafsdóttir, Per Larsen, Rasmus R. Paulsen, Rasmus Larsen, Chad A. Perlyn, Sven Kreiborg. Automatic assessment of craniofacial growth in a mouse model of Crouzon syndrome. Accepted for the American Cleft Palate Craniofacial Association’s 66th Annual Meeting and Pre-Conference Symposium, 2009. [195] Signe S. Thorup, Hildur Ólafsdóttir, Tron A. Darvann, Nuno V. Hermann, Per Larsen, Rasmus R. Paulsen, Chad A. Perlyn, Gillian M. Morriss-Kay, Sven Kreiborg, Rasmus Larsen. Multivariate Analysis of Variance: Finding significant growth in mice with craniofacial dysmorphology caused by the Crouzon mutation. Accepted for Proceedings of the 8th FrenchDanish Workshop on Spatial Statistics and Image Analysis in Biology. 2010. [49] Tron A. Darvann, Nuno V. Hermann, Sune Demant, Per Larsen, Hildur Ólafsdóttir, Signe S. Thorup, Marek Zak, Angelo B. Lipira, Alex A. Kane, Daniel Govier, Helena Schatz, Daniel Rueckert, Sven Kreiborg. Automated Quantification and Analysis of Facial Asymmetry in Children with Arthritis in the Temporomandibular Joint. Accepted for International Symposium on Biomedical Imaging, 2011. [78] Michael S. Hansen, Signe S. Thorup, Simon K. Warfield. Polyaffine Parametrization of Image Registration based on Geodesic Flows. Accepted for Mathematical Methods in Biomedical Image Analysis 2012. Other Material • Signe S. Thorup, Michael S. Hansen, Tron A. Darvann, Nuno V. Hermann, Per Larsen, Rasmus R. Paulsen, Sven Kreiborg, Rasmus Larsen, Simon. K Warfield. Poster on 2D Single Image Super-Resolution, Summer school 2011, Bornholm, Denmark. • Signe S. Thorup, Tron A. Darvann, Nuno V. Hermann, Per Larsen, Hildur Ólafsdóttir, Rasmus R. Paulsen, Alex A. Kane, Dan Govier, Lun-Jou Lo, Sven Kreiborg, Rasmus Larsen. Poster on Cleft Variation (PCA/SPCA) and Cleft Prediction (linear regression), Summer school 2010, Holar, Iceland.
Recherches de facteurs génétiques impliqués dans l'élaboration du rendement sous contrainte hydrique chez le tournesol Helianthus annuus par génétique d'association et analyse de liaison dans une population recombinante

La disponibilite en eau est un facteur essentiel pour le rendement des principales especes cultivees. Le tournesol figurant parmi les especes d'importance economique majeure est concerne par cet enjeu. L'objectif de cette these est d'identifier les regions genomiques permettant d'expliquer la variabilite du rendement sous contraintes hydriques. Une approche de genetique d'association a ete menee sur un panel de 384 lignees cultivees et elites evalue en combinaison hybride sur un reseau experimental de 17 environnements. L'analyse separee de chaque environnement a permis d'identifier 157 marqueurs associes avec au moins un caractere grâce a l'utilisation d'un modele prenant en compte la structuration du panel en deux groupes : restauratrices de fertilite et mainteneuses de sterilite mâle. Parmi ces marqueurs significatifs, 34 etaient associes avec un caractere lie a la productivite, mais ceci, le plus souvent, de maniere specifique a un environnement, soulignant ainsi l'importance de l'interaction genotype-environnement. Un modele eco-physiologique simulant la performance de genotypes en fonction des conditions environnementales, a permis de caracteriser le stress hydrique au sein du reseau. En utilisant des varietes temoins definies dans le modele, un index de stress a ete estime pour chaque environnement. La reponse du panel a cet index a ensuite ete testee en genetique d'association permettant d'identifier de nouveaux loci impliques dans la tolerance au stress hydrique et la stabilite du rendement. Enfin, La detection de QTL a partir d'une population bi-parentale a permis de confirmer certaines zones detectees en genetique d'association et d'en decouvrir de nouvelles.
Insect community response to switchgrass intercropping and stand age of loblolly pine (Pinus taeda) plantations

Intercropping switchgrass (Panicum virgatum) between rows in managed pine stands is a potential, emerging method for biofuel feedstock production in forestry systems. Switchgrass intercropping likely alters vegetation characteristics within a stand by increasing herbaceous vegetation cover and thus influences insect communities positively. However, its effect may vary with stand age, which often determines canopy closure and vegetation structure within a stand: effects of switchgrass intercropping may be stronger in old pine stands with a closed canopy than in young pine stands with an open canopy. We examined how switchgrass intercropping and stand age, namely 3–4‐year‐old pine (YPine) and 8–9‐year‐old pine (OPine), influenced insect abundance and diversity in loblolly pine (Pinus taeda) stands in Mississippi, U.S.A. , during May to August 2013–2014. We captured insects at 36 locations throughout 12 stands (three stands per each of four treatments; intercropping and non‐intercropping treatment in YPine and OPine stands), using pan traps. Abundance and family level richness were greater in YPine stands and Shannon–Wiener diversity and evenness at family level was higher in OPine stands both years. However, insect abundance and diversity did not differ between intercropping and non‐intercropping treatments. Community composition was also influenced by stand age, which explained > 90% of constrained inertia, rather than switchgrass intercropping. Our findings suggest that switchgrass intercropping is unlikely to significantly affect insect communities in managed pine stands, whereas stand age, as well as associated successional changes, can be a main factor affecting insects, as often observed in other animal taxa in managed pine landscapes.
Anatomia ecológica e potencial econômico da madeira de espécies nativas da Mata Atlântica, Serra da Jiboia, Bahia, Brasil

Esse trabalho teve como objetivo contribuir para o conhecimento da anatomia do lenho de especies arboreas da Mata Atlântica, discutindo seu valor ecologico/funcional, alem de qualificar estas especies para geracao de energia e/ou fabricacao de papel, baseando-se nos valores derivados das dimensoes das fibras e na densidade aparente. A Serra da Jiboia e uma das areas indicadas como prioritarias para conservacao da Mata Atlântica e classificada como de extrema importância biologica no quesito vegetacao. Foram coletadas de tres a dez amostras de 25 especies nesta area, localizada no municipio de Elisio Medrado, Bahia. Considerou-se a porcao entre 1-3 cm a partir da casca para confeccao de macerado, das lâminas histologicas e afericao da densidade aparente. Os resultados estao apresentados em dois capitulos, e dois apendices. No capitulo 1, examinou-se a existencia de tendencias ecologicas para a Mata Atlântica da Serra da Jiboia, registrou-se alta frequencia para aneis de crescimento distintos, porosidade difusa, ausencia de arranjo dos vasos, presenca simultânea de vasos solitarios e multiplos, placa de perfuracao simples, comprimento dos elementos de vasos maior que 350 m, fibras com areola das pontoacoes simples a reduzida, presenca de fibras nao septadas, comprimento da fibra entre 900-1600 m, 4-12 raios por milimetro, raios e elementos axiais nao estratificados e presenca de inclusoes inorgânicas. A maioria destas caracteristicas foi interpretada como tendencias ecologicas para a Mata Atlântica atraves da discussao com a literatura sobre seus significados funcionais e a correlacao destes com as caracteristicas ambientais desse ambiente. Uma menor quantidade foi avaliada como decorrente das tendencias evolutivas gerais para as angiospermas. A area de conducao, indice de vulnerabilidade e mesomorfismo apresentaram grande variacao, trabalhos mais integrativos, envolvendo a anatomia da madeira, que considerem outros aspectos das plantas, devem ser desenvolvidos para uma melhor compreensao das tendencias ecologicas, bem como da variacao que se contrapoem a esta. No capitulo 2, no qual e feita a qualificacao anatomica e fisica da madeira para fabricacao de papel e/ou producao de energia, quatro valores derivados – fracao parede, coeficiente de flexibilidade, indice de Runkel e indice de enfeltramento – e a densidade aparente foram mensurados. Nenhuma especie apresentou todos os valores derivados otimos para a producao de papel, embora se considerado cada valor derivado isoladamente muitas delas podem ser qualificadas positivamente para este fim. A maioria das especies apresentou-se aptas a geracao de energia por exibirem fracao parede, indice de Runkel e densidade aparente alta e baixo coeficiente de flexibilidade, destacando-se Aspidosperma discolor, Helicostylis tomentosa, Miconia amoena e Myrsine guianensis. Conclui-se, portanto, que a Serra da Jiboia apresenta-se como uma area em potencial para estudos de manejo sustentavel de madeiras economicamente viaveis.
Developing flow-ecology relationships: implications of nonlinear biological responses for water management.

Empirical relationships between stream flow and ecological responses (flow–ecology relationships) are essential for establishing environmental flows and evaluating tradeoffs between instream values and out-of-stream uses. Establishing the shape of flow–ecology relationships (i.e. slope, linearity versus nonlinearity) is particularly important to avoid crossing ecological thresholds in water management. This review focuses on ecological responses to discharge at low summer flows when out-of-stream water demand is often highest, and identifying ecological contexts where nonlinearities are most likely. Most physical attributes (temperature, dissolved oxygen, available habitat) and ecological responses (energy flow, fish survival, recruitment, community structure) show at least some evidence of nonlinear relationships with flow, although assumptions of linearity may be reasonable across limited discharge ranges which may include low flows. Nonlinearities are most likely in systems that are near existing thresholds (e.g. cold-water transitional fish communities that are close to upper thermal tolerances). The probability of nonlinearities is likely to increase under future landuse and climate change scenarios, particularly in combination with other stressors, such as eutrophication, which may greatly accelerate temperature-related decline in dissolved oxygen under climate warming. Managers need to anticipate changes in flow–ecology relationships and develop management systems that are robust to change. Field programmes to establish the slope and linearity of local flow–ecology relationships are essential for regional management, but developing generalisable flow–ecology relationships that are transferrable to regions with limited resources also needs to be a priority. Generalised relationships can be generated through meta-analysis of empirical flow–ecology relationships, and may prove especially useful if they can capture how environmental and ecological context (channel size and morphology, landuse, flow regime, antecedent conditions, habitat or taxonomic guild) affect flow–ecology relationships. For instance, linking empirical data from flow–ecology relationships to available habitat predicted by physical habitat simulation models (e.g. PHABSIM) may provide a better mechanistic basis for modelling ecological responses, while providing much needed validation for habitat simulation approaches. This would also help bridge the gap between emerging holistic environmental flow modelling approaches and more traditional habitat simulation methods.
Response of Nitrogen Metabolism in Pak-choi Plants Treated with Different Sodium Selenate (Na2SeO4) Concentrations

Currently, biofortification breeding programs are being conducted to increase the selenium (Se) content of crops. Se is an element essential to humans and is mostly acquired via consumption of vegetables. However, the effects of Se on the main plant metabolisms such as nitrogen metabolism are unclear. The main objective of this study was to determine the effect of the application of different concentrations of Se (10, 20, and 30 μM) as Na2SeO4 on nitrogen metabolism in Pak-choi grown hydroponically. Supplemental Se increased all enzyme activities analyzed, including nitrate reductase (NR), glutamine synthetase (GS), and glutamate synthase (GOGAT). In 20-μM Se treatment of two cultivars, the fresh weight was significantly increased and the foliar NO3 content was significantly decreased. Compared to the control, the data on Se treatments showed stronger activations of NR, GS, and GOGAT, as well as greater concentrations of total ammonium, amino acid, and protein, and a higher nitrogen use efficiency, resulting in increased biomass production. This suggests the mechanism of Se applied to Pak-choi to decrease NO3 content was due to increasing nitrogen metabolism and protein synthesis to biomass.
The Genetic Program of Myc-potentiated Apoptosis: Systems Development

Myc is a powerful oncogene frequently deregulated i n cancer yet deregulated Myc alone does not lead to cellular transformation due to the intrinsic safety mechanism of deregulated Myc potentiating apoptosis. The mechanism by which Myc potentiates apoptosis remains unclear, however, because the regions of Myc essent ial for apoptosis are also required for Myc to function as a regulator of gene transcriptio n, it is thought that Myc’s role in apoptosis is a function of its regulation of an apoptotic gen etic program. We hypothesize that under apoptotic conditions, Myc differentially binds and/ or regulates a specific cohort of genes to potentiate apoptosis. The foremost approach to addr essing this hypothesis is the employment of ChIP-chip coupled with expression microarray ana lyses. Here, using the MCF10A breast epithelial and SHEP neuroblastoma cell lines, we de veloped and characterized two independent human systems for subsequent ChIP-chip and expression array analyses to elucidate the genetic program of Myc-potentiated ap optosis.
A study of a novel self-fertility mechanism in the hermaphroditic nematode Rhabditis sp. SB347

Germ cell development and gametogenesis are essential for the continuity of future generations in most eukaryotic organisms, including humans. One well-established system for studying the complex mechanisms of gametogenesis is the nematode species, Caenorhabditis elegans. The fact that C. elegans hermaphrodite germlines undergo different cellular development at the same life stage in a linear progression makes C. elegans a model system for the study of the conversion of uncommitted germ cells into either oocytes or sperm. C. elegans hermaphrodite produces spermatocytes during the final larval stage and then makes a one-time switch over to oogenesis as the worm enters adulthood. Recently our lab made the surprising discovery that hermaphrodites of another nematode species, Rhabditis sp. SB347, evolved an alternative mechanism for achieving self-fertility. In Chapter one, we describe that the germline in R. sp. SB347 hermaphrodites is capable of producing both sperm and oocytes from the final larval stage throughout adulthood. Along the length of SB347 hermaphrodite germline, we found clusters of distinct “mystery cells” that divide mitotically outside of stem cell. These “mystery cells” serve as spermatocyte progenitors and share features of spermatogonial cells that are key components of sperm production in other organisms, including Drosophila, mice and humans. Our finding is significant for the understanding of germ cell development because it reveals a completely new reproductive characteristic that is not present in C. elegans but in other model organisms. In Chapter two, we look at further characterization of spermatogonial cells using a key molecular player known as fem-3 binding factor (FBF). Previously described to regulate both mitosis/meiosis switch and oocyte/sperm determination in Caenorhabditis elegans, FBF belongs to PUF (Pumilio and FBF) protein family and shares a conserved role of germline stem cell regulation. We report the presence of FBF in both the distal germline and the spermatogonia, and unexpectedly, in late maturing oocytes. Our results highlight SB347 spermatogonial cells as an intermediate stage of partially committed spermatocyte progenitors that remain features of germline stem cells. Through this study of the first reported case of spermatogonial cells in the phylum nematode, we hope to extend our knowledge of germline stem cell development to decipher features of stem cell differentiation and provide more insights with broader, medical implications.