Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeted Sequencing Of Chromosome 9 Genes Associated With Papillary Type 1 Renal Cell Carcinoma

We have completed a targeted sequencing study of 6 patient Papillary Type 1 tumors. Fragment libraries were created for 456 exons of 43 genes on the p-arm of chromosome 9 between reference positions 1,051,050-14,150,350 using biotinylated DNA hybridization probes to enrich 112.5 kb of sequence. The selected fragments were collected, concentrated, and subjected to a second round of hybridization, capture, wash, and amplification followed by sequencing on the Ion Torrent PGM using the 318 v2 chip. Analysis was performed using the GenomAnalytics (GenomOncology, Westlake, OH) server and all findings were confirmed by manual curation of the sequence using the Integrated Genome Viewer (Broad Institute, Canbridge, MA). We previously identified significant copy number losses specific to Papillary Type 2 renal tumors in the GLDC, SLC1A1, and CDC37L1 genes of each tumor. Also, we identified 3 single nucleotide substitutions that were identical in every tumor sample within the coding regions of 3 genes (TPD52L3, PDCD1LG2 and KIAA0020) in this genomic domain. Papillary Type 1 tumors were sequenced to determine if they exhibit different single nucleotide and copy number variants than those identified in Papillary Type 2 samples. The long-range goal is to develop a low cost, highresolution test requiring minimal substrate to rapidly distinguish among Papillary Type 1 and Type 2 cancers using small biopsy specimens or fine needle aspirates.
Onset of a vector borne disease due to human circulation - uniform, local and network reproduction ratios

We study the effect of human circulation on the onset of an epidemics for a arboviral (mosquito-borne) illness such as dengue. The underlying dynamics on a metapopulation is given by a classical SIR (human)/SI (vector) model. We consider three concepts of reproduction numbers: local (for each isolated subsys- tem), uniform or mixing (disregarding movement and non-uniformity in the whole region), and network (coupling the patches via human circulation). Interrelations between the three concepts are obtained. Depending on the biological contact as- sumptions, two types of network models result. In destination type models, the force of infection depends on mosquito density, relative to human population or to area. In origin based models, it is assumed that the transmission is determined by the behaviour of susceptible humans. Archetypal examples can be found where each node has local reproduction ratio less than one, the uniform reproduction number is also less than one, but the network reproduction number is greater than one. This shows that the disease can propagate among the patches solely as a consequence of human circulation. An estimate about the effect of vector control on a given patch is given. The conceptual framework presented here may help decision makers to plan vector control policies and medical care in case of an outbreak.
Atomic structure of the mitochondrial inner membrane AAA+ protease YME1 reveals the mechanism of substrate processing

We present the first atomic model of a substrate-bound inner mitochondrial membrane AAA+ quality control protease, YME1. Our ~3.4 Å cryo-EM structure reveals how the ATPases form a closed spiral staircase encircling an unfolded substrate, directing it toward the flat, symmetric protease ring. Importantly, the structure reveals how three coexisting nucleotide states allosterically induce distinct positioning of tyrosines in the central channel, resulting in substrate engagement and translocation to the negatively charged proteolytic chamber. This tight coordination by a network of conserved residues defines a sequential, around-the-ring ATP hydrolysis cycle that results in step-wise substrate translocation. Furthermore, we identify a hinge-like linker that accommodates the large-scale nucleotide-driven motions of the ATPase spiral independently of the contiguous planar proteolytic base. These results define the first molecular mechanism for a mitochondrial inner membrane AAA+ protease and reveal a translocation mechanism likely conserved for other AAA+ ATPases.
DIFFERENTIAL EFFICACY OF BORTEZOMIB IN SUBTYPES OF DIFFUSE LARGE B‐CELL LYMPHOMA (DLBL): a PROSPECTIVE RANDOMISED STUDY STRATIFIED BY TRANSCRIPTOME PROFILING: REMODL‐B

DLBL subtypes identified by patterns of gene expression correspond to germinal center (GCB) or activated (ABC) B‐cells like. The latter demonstrate dysregulation of the NF‐KB pathway. Outcomes of treatment with R‐CHOP are inferior for ABC DLBL in retrospective series. This study investigated whether adding bortezomib (B), a putative NF‐KB inhibitor, can reverse this phenotype.
Production of naringenin from D‐xylose with co‐culture of E. coli and S. cerevisiae

Heterologous production of naringenin, a valuable flavonoid with various biotechnological applications, was well studied in the model organisms such as Escherichia coli or Saccharomyces cerevisiae. In this study, a synergistic co‐culture system was developed for the production of naringenin from xylose by engineering microorganism. A long metabolic pathway was reconstructed in the co‐culture system by metabolic engineering. In addition, the critical gene of 4‐coumaroyl‐CoA ligase (4CL) was simultaneously integrated into the yeast genome as well as a multi‐copy free plasmid for increasing enzyme activity. On this basis, some factors related with fermentation process were considered in this study, including fermented medium, inoculation size and the inoculation ratio of two microbes. A yield of 21.16 ± 0.41 mg/L naringenin was produced in this optimized co‐culture system, which was nearly eight fold to that of the mono‐culture of yeast. This is the first time for the biosynthesis of naringenin in the co‐culture system of S. cerevisiae and E. coli from xylose, which lays a foundation for future study on production of flavonoid.
Biomarcadores sanguíneos para a doença de Alzheimer : avaliação da expressão gênica da ADAM10 e de micro- RNAs

8 APRESENTAÇÃO . 12 1. INTRODUÇÃO . 14 1.1 Envelhecimento populacional e alterações cognitivas . 14 1.2 Fisiopatologia da DA . 15 1.3 ADAM10 e DA . 18 1.4 micro-RNAs e DA . 26 1.5 Biomarcadores sanguíneos para DA . 30 2. OBJETIVOS . 34 3. REFERÊNCIAS BIBLIOGRÁFICAS . 36 4. MANUSCRITOS . 46 4.1 MANUSCRITO I . 46 4.2 MANUSCRITO II . 65 5. CONCLUSÕES . 95 6. ANEXOS . 97 6.1 MANUSCRITO III . 97 6.2 MANUSCRITO IV . 117
Assessment of morpho-anatomical traits of red fescue (Festuca rubra L.) germplasm differing in origin.

Thirty-eight accessions of red fescue (Festuca rubra L.), collected from different bioclimatic regions of Ukraine and Latvia, were evaluated for 16 quantitative traits in the Central Lowland of Lithuania. The research was aimed to evaluate morpho-anatomical traits of the populations and reveal the relationship with their geographic origin. The data collected indicated that F. rubra populations differing in origin were quite similar in their morphology. However, significant differences in length of lemma, flag and stem leaf laminas, number of leaf ribs, veins and sclerenchyma bundles were established between the Ukrainian and Latvian populations. Moreover, a greater variation of morpho-anatomical traits was noted for the populations from southern part of F. rubra distribution range. Principal component analysis enabled us to differentiate 7 most promising populations (of which 6 were from Ukraine) based on the most important pre-breeding traits such as seed number per plant and plant height.
Determination of complete mitogenome sequence for Eastern Asian population of Cheilonereis cyclurus (Harrington, 1897) (Polychaeta: Nereididae)

Abstract Complete mitogenome sequence for eastern Asian population of Cheilonereis cyclurus (Polychaeta: Nereididae) was determined for the first time. The length of circular genome of C. cyclurus is 14,917 bp including 13 protein-coding genes, two rRNA genes, 22 tRNA genes, and a non-coding region of 383 bp. The gene order of C. cyclurus is identical to that of the following four nereidid species: Hediste diadroma, Namalycastis abiuma, Paraleonnates uschakovi, Tylorrhynchus heterochaetus. The phylogenetic position of C. cyclurus compared to 16 selected polychaetes was conducted and present species is closely related to the clade containing Perinereis nuntia, P. aibuhitensis, and Platynereis dumerilii with high bootstrap value.
Assessment of Genetic Diversity among Pigeon pea Male Sterile lines and Popular Cultivars using SSR Markers

In the present study genetic diversity studies have been carried out using twenty five SSR markers in a set of pigeonpea genotypes comprising of male sterile lines and popular cultivars. The primers amplified a total of 99 bands with highest PIC of 0.79. The SSR markers grouped the genotypes into four clusters based on UPGMA and Principal Component Analysis. The male sterile lines along with PRG158 were grouped into three clusters while, the remaining cultivars formed a distinct cluster indicating the narrow genetic base of released cultivars. PCA revealed that phenotypic variation explained by the SSRs ranged from 4.7% to 49.6% with PC1 and PC2 accounting for 49.6% and 30.8% of total variation. The study indicated the existence of diversity between the male sterile lines and the popular cultivars which can be exploited for hybrid breeding program.
Immigrant and extrinsic hybrid seed inviability contribute to reproductive isolation between forest and dune ecotypes of Epipactis helleborine (Orchidaceae)

Reproductive isolation caused by divergent natural selection arising from differences between ecological environments or ecological interactions represents a major mechanism contributing to speciation, but its relative importance is poorly known. In this study, controlled reciprocal crossings and seed germination experiments were combined with genetic and morphometric analyses to test the hypothesis that previously described differences in mycorrhizal communities between forest and dune ecotypes of Epipactis helleborine were sufficiently strong to create complete reproductive isolation between the two ecotypes. Molecular analyses using 770 SNP markers showed that the two ecotypes were genetically distinct and that populations of the dune ecotype were genetically impoverished compared to populations of the forest ecotype. Morphologically, the two ecotypes were also significantly different, with plants of the dune ecotype generally being smaller than plants of the forest ecotype. The results further showed that immigrant seeds had a significantly lower probability of protocorm formation than native seeds, indicating strong immigrant inviability. Although both ecotypes were able to cross easily and to produce a large number of viable seeds, hybrid seeds showed significantly lower protocorm formation than pure seeds, further contributing to reproductive isolation. Overall, these results indicate that interfertile populations of a widespread orchid adapting to contrasting environments diverge as a consequence of concurrent selection acting against immigrants and hybrids and suggest that mycorrhizal fungi can play a role in the early stages of plant speciation.
A Rabbit model for evaluating the efficacy of recombinant adenovirus vaccine expressing E0-E2 antigens of classical swine fever virus

This study investigated the efficacy of a recombinant adenovirus vaccine expressing E0-E2 antigens (rAd-E0-E2) of the classical swine fever virus (CSFV) and determined its minimum effective dose in rabbits. Forty rabbits were randomly divided into five groups. Three groups were immunized intramuscularly with rAd-E0-E2 at doses of 107.0, 106.0 and 105.0 IFU, respectively. CSFV C strain was administered to one group and saline to another group (negative control). Fourteen days after immunization, the animals were challenged intramuscularly with CSFV C strain. Stereotypical thermal responses were monitored to assess the protective efficacy of the vaccine. No typical thermal response was observed in either the 107.0 IFU or CSFV C strain groups. Mean spleen weight to body weight ratios in these groups were 0.055% and 0.05%, respectively, no evidence of hyperemia was observed in the splenic tissue, and no CSFV C strain was detected in the spleens by either RT-PCR or indirect fluorescent antibody (IFA) test. In the 106.0 IFU group, 6/8 rabbits showed typical thermal response and the spleen weight to body weight ratio was 0.074%. Further, in 6/8 rabbits, the splenic tissues showed hyperemia and virus was detected by IFA. In both 105.0 IFU and control groups, all animals developed fever and the spleen weight to body weight ratios were 0.099% and 0.102%, respectively. Severe hyperemia was observed and the virus was detected in the splenic tissue by RT-PCR and IFA. In conclusion, rAd-E0-E2 confers protection against CSFV C strain infection, and a rabbit model for evaluating the efficacy of the vaccine has been successfully established. The minimum effective dose in rabbits in this study was 107.0 IFU.
Acute Pro-inflammatory Immune Response Following Different Resistance Exercise Protocols in Trained Men

The successful regeneration of muscle tissue is dependent upon the infiltration of phagocytic CD14++CD16monocytes that support the proliferation and differentiation of myogenic precursor cells. Physiologically, the magnitude of the cellular response following resistance exercise is dictated by the level of receptor expression on the plasma membrane of the monocyte, as well as the secretion of their cognate ligands from tissue resident cells. However, it remains unclear whether the innate pro-inflammatory immune response varies with different resistance training protocols, and how it may impact recovery and the muscle remodeling process. Therefore, the purpose of this investigation was to examine temporal changes in the expression of chemotactic and adhesion receptors following an acute bout of high-volume, moderate-intensity (VOL) versus high-intensity, low-volume (HVY) lower-body resistance exercise in experienced, resistance trained men. Changes in receptor expression were assessed in conjunction with plasma concentrations of MCP-1, TNFα, and cortisol. Ten resistance-trained men (90.1 ± 11.3 kg; 176.0 ± 4.9 cm; 24.7 ± 3.4 yrs; 14.1 ± 6.1% body fat) performed each resistance exercise protocol in a random, counterbalanced order. Blood samples were obtained at baseline (BL), immediately (IP), 30 minutes (30P), 1 hour (1H), 2 hours (2H), and 5 hours (5H) post-exercise. Analysis of target receptor expression on CD14++CD16monocytes was completed at BL, IP, 1H, 2H and 5H time points via flow cytometric analysis. Plasma concentrations of myoglobin, and LDH AUC were significantly greater following HVY compared to VOL (p = 0.003 and p = 0.010 respectively). Changes in plasma TNFα, MCP-1, and expression of CCR2, CD11b, and GCR on CD14++CD16monocytes were similar following HVY and VOL. When collapsed across groups, TNFα was significantly increased at IP, 30P, 1H and 2H post-exercise
FGF/MAPK signaling sets the switching threshold of a bistable circuit controlling cell fate decisions in ES cells

Intracellular transcriptional regulators and extracellular signaling pathways together regulate the allocation of cell fates during development, but how their molecular activities are integrated to establish the correct proportions of cells with particular fates is not known. Here we study this question in the context of the decision between the epiblast (Epi) and the primitive endoderm (PrE) fate that occurs in the mammalian preimplantation embryo. Using an embryonic stem (ES) cell model, we discover two successive functions of FGF/MAPK signaling in this decision. First, the pathway needs to be inhibited to make the PrE-like gene expression program accessible for activation by GATA transcription factors in ES cells. In a second step, MAPK signaling levels determine the threshold concentration of GATA factors required for PrE-like differentiation, and thereby control the proportion of cells differentiating along this lineage. Our findings can be explained by a simple mutual repression circuit modulated by FGF/MAPK signaling. This may be a general network architecture to integrate the activity of signal transduction pathways and transcriptional regulators, and serve to balance proportions of cell fates in several contexts.
Optimal Media for In-Vitro Regeneration of Two Local Genotypes of Chili Pepper (Capsicum annuum L.) from West Sumatera

Genetic engineering strategy in chilli pepper ( Capsicum annuum L.) has been applied so far in order to improve its genetic capacity for instance against some important diseases. This strategy needs an established system for calli preparation as well as transformant regeneration. In most cases, this necessity is genotype dependent especially for some local genotypes. Based on this, we optimized media for calli induction, shoot and root regeneration of our three local cultivars namely Kampung, Kopay and Trisula. Media combinations basically were composed of MS and combined with some growth factors for instance IAA, BAP, NAA and TDZ with different combinations for each calli induction, shoot and root regeneration. All media compositions were supplemented with 30 GL -1 sucrose. The best medium for calli induction was MS media supplemented with 4 mgL -1 BAP, 0.5 mgL -1 IAA and L2 vitamin (Thiamin-HCl and Pyrodoxine-HCl). While the best medium for shoot induction and elongation was MS supplemented with 1mgL -1 BAP, 5 mgL -1 AgNO 3 , 2 mgL -1 GA 3 , 2 mgL -1 Calcium Pantotenate and L2 vitamin. Furthermore, the best medium for root induction and elongation was WPM (Woody Plant Medium) supplemented with 0.4 mgL -1 NAA. This finding should provide optimal media for calli induction and shoot-root regeneration for the three local cultivars Kampung, Kopay and Trisula.
Exploring the Neural Control of Axolotl Limb Regeneration

Nerve dependence is a phenomenon observed across a stunning array of species and tissues. From zebrafish to fetal mice to humans, research across various animal models has shown that nerves are critical for the support of tissue repair and regeneration. Although the study of this phenomenon has persisted for centuries, largely through research conducted in salamanders, the cellular and molecular mechanisms of nerve dependence remain poorly-understood. Here we highlight the near-ubiquity and clinical relevance of vertebrate nerve dependence while providing a timeline of its study and an overview of recent advancements towards understanding the mechanisms behind this process. In presenting a brief history of the research of nerve dependence, we provide both historical and modern context to our recent work on nerve dependent limb regeneration in the Mexican axolotl.
Habitat use, nest-sites and chick diet of Grey Partridge Perdix perdix on hill farms in north east England

ABSTRACT Capsule: Breeding Grey Partridges Perdix perdix on hill farms preferred Soft Rush-infested rough grazing which provided nesting cover and invertebrates for foraging chicks. Aims: To measure habitat use, nest sites, chick diet and breeding productivity of Grey Partridge on hill farms in north east England. Methods: We measured actual habitat use of radio-tagged individuals in relation to its availability both within home ranges and over the wider study area. Nesting habitat and breeding productivity data were collected from radio-tagged pairs. Faecal samples from roost sites of broods were collected to assess chick diet. Results: Grey Partridges preferred rough grazing habitats. Sixty-nine per cent of nests were found in rough grazing with females preferring to nest in tall rushes which provided cover. Chick diet differed between habitats and in relation to brood age. In rough grazing, sawfly larvae were the most numerous item eaten by young (46%) and older broods (27%). Conclusion: On hill farms, breeding Grey Partridges preferred rough grazings, where broods preferred sawfly larvae. It is important that rush-infested rough grazings are not agriculturally improved and grazing regimes that provide abundant sawfly larvae are practised.
Fast and reliable phenotyping of leaf functions: a tool for water stress tolerance evaluation

A protocol and a related physiological tool to discriminate drought tolerant apple genotypes in a reliable, fast way were assessed. Trials were carried out in two years and two sites: Bologna (Italy) and Montpelier (France). Potted trees from 17 genotypes grafted on Pajam 2 rootstocks were used. After sufficient shoot development, three pots genotype -1 were maintained at field capacity, while three other plants were subjected to water stress, by keeping their soil water content at about 40% of field capacity. Leaf net photosynthesis, stomatal conductance, electron transport rate via chlorophyll fluorescence, air and leaf temperature were measured on each plant. By a multi-variate semi-mechanistic approach, a new physiological index (I PL ) was developed, tested and validated, which appeared strongly and linearly related to net photosynthesis. All the validation tests suggest I PL can be used as a reliable and fast (about 30” leaf -1 ) photo-assimilation index. The response of apple genotypes to water shortage was evaluated considering the percent reduction in leaf parameters when plants were subjected to water stress. These percentages were subjected to a Principal component analysis (PCA) and the case coordinates of the main components F1 and F2 were clustered via a K-means clustering. Each genotype was placed in one of 3 pre-defined classes: drought susceptible, intermediate, tolerant. The same clustering was performed using only the I PL percent reduction. Using either F1, F2 or the less time consuming I PL as discriminant factors, about 53% of the genotypes were assigned to the same class in the four cases (2 years and 2 sites). I PL could be useful to assess leaf functioning under varying environmental conditions, like water availability. However, as only half of the genotypes behaved in the same way in the 4 cases, further research should be performed in order to set up a replicable water stress imposition protocol.
Contrasting Pollination Efficiency and Effectiveness among Flower Visitors of Malva Sylvestris, Borago Officinalis and Onobrychis Viciifolia

Biotic pollination is an important factor for ecosystem functioning and provides a substantial ecosystem service to human food security. Not all flower visitors are pollinators, however, and pollinators differ in their pollination performances. In this study, we determined the efficiencies of flower visitors to the plant species Malva sylvestris , Borago officinalis and Onobrychis viciifolia by analysing stigmatic pollen deposition. We further calculated pollinator effectiveness by scaling up single-visit pollen deposition using visitation frequency. Flower-visitor groups differed in their efficiencies at the single-visit level and not all of them deposited more pollen compared to unvisited stigmas. Bumblebees tended to be most efficient in depositing pollen per single visit across the three plant species. Due to the by far highest visitation frequencies, Apis mellifera showed the highest effectiveness in depositing pollen per hour for M. sylvestris and B. officinalis , but not for O. viciifolia , for which the Bombus lapidarius complex was both the most frequent and the most effective pollinator group. Hence, the most frequent flower visitors were most effective in our study. For non-dominant pollinator groups, however, visitation frequencies contributed disproportionally to pollinator effectiveness. Thus, combining pollen deposition per single-visit with visitation frequency is necessary to reveal true pollinator performance and to better understand flower-visitor interactions. PLEASE NOTE: Supplementary files to this article can be found in the left menu of this website.