Miracle-dz/UniFAR-FTUs huggingface dataset:
Exploring the relation between the intracellular fate and biological activity of oligodeoxynucleotide containing nanoparticles

Antisense deoxyoligonucleotides (ODNs) show potential in the treatment of genetic disorders, cancer and viral infections. Antisense ODNs need to reach the target tissue in an intact way, since their sequence is crucial for obtaining the desired antisense effect. Naked ODNs only poorly cross cellular membranes. Also, naked phospodiester ODNs (PO-ODNs) are very sensitive for degradation. Therefore, in non-viral gene therapy, the ODNs are delivered as complexes with either cationic liposomes or cationic polymers. This increases the protection of PO-ODNs against enzymatic degradation and their cellular uptake and intracellular trafficking. We developed an easy method, based on Fluorescence Correlation Spectroscopy (FCS) and Fluorescence Resonance Energy Transfer (FRET) to follow the degadation of both naked and complexed PO-ODNs in buffer and in living cells. By using FRET-FCS, a clear correlation can be found between the protection of PO-ODNs against enzymatic degradation and their obtained biological effect. In this review we will give an overview of the potential of FRET-FCS and the different non-viral gene delivery systems that we studied so far using this technique.
Inhibitory effects of grape seed extract on the formation of heterocyclic aromatic amines in beef and chicken meatballs cooked by different techniques

ABSTRACT Heterocyclic aromatic amines (HCAs) are mutagenic compounds formed when foods are cooked at high temperatures. The objective of this study was to examine the efficiency of the grape seed extract (GSE) on the formation of HACs in beef and chicken meatballs cooked by four different cooking techniques (oven roasting, pan cooking, charcoal-barbecue, and deep-fat frying). Six HCAs; 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 9H-pyrido[3,4-b]indole (norharman), and 1-methyl-9H-pyrido[3,4-b]indole (harman) were measured. In addition, cooking losses, total phenolics, and radical-scavenging activities were determined. In the beef meatballs, the highest inhibitory effects were 69% for norharman, 65% for IQ, 65% for PhIP, and 59% for MeIQx, while in chicken meatballs were 73% for PhIP, 52% for IQ, 37% for MeIQx, and 31% for norharman. Results of this study suggested that addition of GSE can be an important factor in decreasing the levels of total HCAs in charcoal-barbecued beef meatballs (65%) and oven roasted chicken meatballs (37%).
Nematode communities : bio-indicators of soil quality in conventional and conservation agricultural cropping systems

Due to limited and fragmented information about the effects of conservation agriculture (CA) on nematode assemblages worldwide, the soil quality of such ecosystems as well as that in conventional (CTA) maize fields and adjacent natural-veld (NV) areas were investigated. Root and rhizosphere soil samples were obtained from 24 ecosystems (2 maize fields (CA & CTA) and 2 NV from six localities) during the 2012/2013 growing seasons in the North-West and Free State Provinces of South Africa. Standard techniques were used to extract nematodes from root and soil samples. Morphological and molecular (only for Meloidogyne spp.) techniques were used to identify nematodes to genus/species (plant-parasitic nematodes) and/or genus/family (non-parasitic nematodes) levels. In total, 13 plant-parasitic genera, 21 species and one subspecies were identified during this study from root and soil samples from both maize and NV ecosystems. Of these, 10 genera and 11 species as well as one subspecies were associated with maize crops under CA. In terms of non-parasitic nematodes, a total of 37 genera as well as individuals from seven families were present in soil rhizosphere samples from maize fields and NV ecosystems. Of these, 27 genera and individuals from seven families were present in soil from maize under CA. Nematode (plantparasitic and non-parasitic) community structures and population levels, however, differed between the maize fields under CA and CTA as well as from those in NV ecosystems. Interestingly, fields under CA had substantially higher prominence values (PV) for Rotylenchulus parvus (50 g roots) and Pratylenchus spp. (5 g roots) compared to those for CTA and NV. However, higher PV values for Meloidogyne spp. were evident in maize roots from CTA fields than those under CA. Conversely, soils from NV ecosystems generally maintained higher PV values and diversity for most of the nonparasitic nematode genera/families. In terms of nematode-food web structures, the majority of the soils sampled during this study represented resource-depleted soil
A method for quantifying the force dependence of initiation by T7 RNA polymerase

To access the genetic code to be transcribed to RNA, RNA polymerases must first open a "transcription bubble" in the DNA. Structural studies suggest that the minimal model of initiation by T7 bacterophage RNA polymerase (T7 RNAP) consists of two distinct steps: initial binding, in which the T7 RNAP binds to and bends the DNA, and opening, achieved by "scrunching" of the DNA. Since both steps involve mechanical deformation of the DNA, both may be affected by downstream DNA tension. Using an oscillating two-bead optical tweezers assay, we have measured the lifetime of single T7 RNAP-DNA initation complexes under tension. Global maximumlikelihood fitting of force-dependent and non-force-dependent versions of this minimal model shows that there is no conclusively discernible force-dependence of initiation in the measured 0-2 pN DNA tension range.
Neighbourhood defence gene similarity effects on tree performance: a community transcriptomic approach

The structure and dynamics of ecological communities are ultimately the outcome of the differential demographic rates of individuals. Individual growth and mortality rates largely result from the interaction between an organism's phenotype and the abiotic and biotic environment. Functional traits have been used extensively over the past decade to elucidate links among phenotypes, demography and community dynamics. A fundamental weakness of most functional trait approaches is the use of ‘soft’ traits associated with resource acquisition to examine how neighbourhood similarity affects tree survival and growth. However, these ‘soft’ traits are unlikely to be good predictors of similarities among co‐occurring species. Less easily measured aspects of organismal function – such as those related to defence – have frequently gone unmeasured. This is particularly problematic for testing important hypotheses in forest ecology, such as the Janzen–Connell hypothesis where focal trees are expected to be at a disadvantage if their neighbours share the same natural enemies. A potential alternative to functional trait approaches is to quantify the transcriptomic or functional genomic similarity of species. Such analyses are now possible in natural systems where de novo transciptome assemblies can be used to conduct functional phylogenomic analyses where homologous gene trees are produced. Using demographic plot data for 21 species from a North American forest dynamic plot, we conduct a community functional phylogenomic analysis of a plant community to elucidate the similarity in defence response genes across species. This similarity was then used to ask whether the similarity in defence genes of heterospecific species in the local neighbourhood of a focal individual tree influences its growth and mortality rates. The results show that individual growth rates are higher when surrounded by dissimilar heterospecific species for 16 of 27 defence genes analysed. Additionally, survival rates are increased when an individual is in a neighbourhood with dissimilar species for 4 of the 27 defence genes studied. Lastly, strong conspecific effects were found in all analyses, underscoring that future analyses investigating the genetic variation and differential expression of defence‐related genes in neighbourhoods may prove important. Synthesis. In summary, this research leverages recent advances in RNA sequencing and bioinformatics to conduct community‐wide transcriptomic analyses and analyses of defence‐related gene similarity across a tree community. The results demonstrate that defence gene similarity in neighbourhoods often does have negative effects on individual demographic performance as predicted by the Janzen–Connell hypothesis.
Flora das cangas da Serra dos Carajás, Pará, Brasil: Nyctaginaceae

This study includes the species of Nyctaginaceae recorded for the cangas of the Serra dos Carajás, Pará State, and provides detailed descriptions, illustrations, and morphological comments of the species in the study area. Four species were recorded: Neea macrophylla and N. oppositifolia occurring in amazonic and periamazonic areas, Guapira venosa and Neea floribunda, with a disjunct distribution between Amazonian Rainforest and Atlantic Forest biomes.
PHYTOCHEMICAL SCREENING OF ARTOCARPUS HIRSUTUS AND ITS ANTIMICROBIAL POTENTIAL

Objective: In the present study, the effort was aimed to evaluate the phytochemical components, antioxidant activity, and antimicrobial activity of Artocarpus hirsutus fruit and leaf. Methods: Each plant materials were extracted with two suitable solvents such as acetone and ethanol. Then, the extracts were tested for the presence of active phytoconstituents and antimicrobial activity. Then, it was subjected to antimicrobial activity against fungal and bacterial strains. Results: The present study suggested that the selected plant extracts of A. hirsutus exhibit major phytoconstituents, such as alkaloids, glycosides, terpenoids, phenols, and saponins. Furthermore, the results showed that acetone fruit extract of A. hirsutus and ethanolic fruit extract of A . hirsutus exhibited significant antimicrobial activity with a maximum zone of inhibition against Staphylococcus aureus and Aspergillus tamarii . Conclusion: The present study also exhibited remarkable antimicrobial activity against all the test microorganisms due to the presence of major bioactive phytochemicals
Inhibitory effect of Panax ginseng and Pleurotus osteratus complex on expression of cytokine genes induced by extract of Dermatophagoides pteronissinus in human monocytic THP-1 and EoL-1 cells

: A recent study reported that Pleurotus ostreatus has the potential to be used as a β -glucan-based cream for supportive complementary therapy of atopic dermatitis. KH054 is a new herbal prescription consisting of P. ostreatus and Panax ginseng . The effects of atopic dermatitis-induced materials on the expression of cytokine genes in human monocytes (THP-1, EoL1) have been examined. Some reports demonstrated that P. ginseng augments the activity of natural killer cells, which plays an important role in innate immunity against infection and tumor development. Monocyte chemotactic protein 1 (MCP-1), interleukin (IL)-6, and IL-8 have important roles in mediating the infiltration of various cells into the skin of atopic dermatitis and psoriasis. The present study investigated whether KH054 on induced IL-6, IL-8, and MCP-1 secretion by house dust mite ( Dermatophagoides pteronissinus ) in THP-1 (human acute monocytic leukemia) and EoL-1(Human eosinophilic leukemia) cell. D. pteronissinus functions in the pathogenesis of allergic diseases, including atopic dermatitis and asthma. The inhibitory effect of KH054 on the induction of IL-6, IL-8, and MCP-1 secretion by D . pteronissinus extract in THP-1 and EoL-1 cells was examined. KH054 potently suppressed the elevated production of IL-6 and IL-8 induced by D. pteronissinus treatment in THP-1 and EoL-1 cells. Based on the present results, KH054 may be useful for developing functional foods to treat atopic dermatitis. keratinocytes, THP-1 cell, clarified the mechanism by which KH054 prevents a mite antigen-mediated chemokine MCP-1, IL-6, and IL-8 expression, which involves in the of
Winter warming effects on tundra shrub performance are species‐specific and dependent on spring conditions

Climate change‐driven increases in winter temperatures positively affect conditions for shrub growth in arctic tundra by decreasing plant frost damage and stimulation of nutrient availability. However, the extent to which shrubs may benefit from these conditions may be strongly dependent on the following spring climate. Species‐specific differences in phenology and spring frost sensitivity likely affect shrub growth responses to warming. Additionally, effects of changes in winter and spring climate may differ over small spatial scales, as shrub growth may be dependent on natural variation in snow cover, shrub density and cryoturbation. We investigated the effects of winter warming and altered spring climate on growing‐season performance of three common and widespread shrub species in cryoturbated non‐sorted circle arctic tundra. By insulating sparsely vegetated non‐sorted circles and parts of the surrounding heath with additional snow or gardening fleeces, we created two climate change scenarios: snow addition increased soil temperatures in autumn and winter and delayed snowmelt timing without increasing spring temperatures, whereas fleeces increased soil temperature similarly in autumn and winter, but created warmer spring conditions without altering snowmelt timing. Winter warming affected shrub performance, but the direction and magnitude were species‐specific and dependent on spring conditions. Spring warming advanced, and later snowmelt delayed canopy green‐up. The fleece treatment did not affect shoot growth and biomass in any shrub species despite decreasing leaf frost damage in Empetrum nigrum. Snow addition decreased frost damage and stimulated growth of Vaccinium vitis‐idaea by c. 50%, while decreasing Betula nana growth (p < .1). All of these effects were consistent the mostly barren circles and surrounding heath. Synthesis. In cryoturbated arctic tundra, growth of Vaccinium vitis‐idaea may substantially increase when a thicker snow cover delays snowmelt, whereas in longer term, warmer winters and springs may favour E. nigrum instead. This may affect shrub community composition and cover, with potentially far‐reaching effects on arctic ecosystem functioning via its effects on cryoturbation, carbon cycling and trophic cascading. Our results highlight the importance of disentangling effects of winter and spring climate change timing and nature, as spring conditions are a crucial factor in determining the impact of winter warming on plant performance.
Growth, phenology, and seed viability between glyphosate-resistant and glyphosate-susceptible hary fleabane

Glyphosate is the herbicide most used worldwide. In cropping systems that rely on repeated applications of glyphosate or cultivate genetically modified soyabean crop, there are numerous cases of glyphosate resistant weeds, including Conyza bonariensis. Differences among competitive ability of Conyza spp. have been found. However, little information is available on the fitness costs related to glyphosate resistance in Conyza bonariensis. We evaluated growth, phenology, and seed viability of glyphosate-resistant (GR) and glyphosate-susceptible (GS) Conyza bonariensis from Brazil, in 2012 (fall/winter) and 2013 (spring/summer). When grown alone, in pots, C. bonariensis GR biotype developed more rapidly than the GS biotype, as evidenced by their earlier bolting, flowering, and seed set. In 2012, GR biotype showed 221.9 cm of plant height compared to 181.1 cm from GS, at the flowering time. In both years, the seed production per plant was superior for GR biotype, showing germination higher than 80% against 66.5% from the GS biotype. Thus, C. bonariensis GR biotype confirmed no fitness penalty also showing characteristics that allow us to infer in superior competitive with the absence of the herbicide. It is important to point out that the biotypes evaluated here have different genetic background and the differences between them may not be fully attributed to the resistance to glyphosate. However, the GR biotype can persist in the environment and outcompete with GS biotypes regardless of further glyphosate selection of pressure.
COMPARISON OF NANOPOROUS SCAFFOLDS MANUFACTURED BY ELECTROSPINNING AND NANOFIBRILLAR COMPOSITE CONCEPT

Fibrillar networks have numerous applications in the biomedical field, which is evident from the extensive research that has been carried out to produce biomedical devices using a variety of manufacturing techniques. Electrospinning in particular has been used to produce devices for tissue engineering, drug release, wound dressing and enzyme immobilisation [1]. Other applications utilising fibrillar networks include filtration, protective clothing, reinforcement in composite materials and sensors [2]. The ability to perform tissue and organ transplantation is limited by the availability of suitable donor tissue and in many cases requires life-long use of immunosuppressant therapy. Manufacturing of biomaterials for tissue engineering is therefore an attractive prospect where many fabrication methods have been tested extensively [3]. This paper compares the morphological characteristics and ability to support cell attachment and growth of scaffolds produced using electrospinning and the nanofibrillar composite (NFC) concept. Two different materials were used for each manufacturing technique, producing four different scaffolds to study and compare.
The Genetic, Molecular, And Cellular Bases Of Unidentified Primary Immunodeficiencies

The immune system is inseparable from every part of human biology. From cell intrinsic mechanisms of pathogen recognition to multi-cellular interactions over vast ranges of time and space, the immune system is both essential for protection from infection and central to the pathogenesis of many diseases. Thus understanding it has long been a focus of biomedical research. While in vitro molecular, biochemical, and cellular techniques as well as complex genetically modified animal models have been developed, these approaches still only approximate true human disease and in vivo human biology. Primary immunodeficiencies are inborn genetic defects of immunity and present rare opportunities to observe, study, and understand how genetic perturbations impact human immunity directly. I therefore clinically and genetically analyzed three patient families with unidentified primary immunodeficiencies. Using whole exome sequencing coupled with in vitro and in vivo biochemical and cellular assays, I identified two novel genetic etiologies of primary immunodeficiency. I first identified de novo missense mutations in GNAI2, the gene encoding the ubiquitously expressed heterotrimeric G-protein Gαi2, in 2 families with life-threating multiorgan system autoimmunity and immunodeficiency to mucocutaneous infections. Gαi2 is essential for chemokine mediated leukocyte migration as well as regulating development, inflammation, and metabolism in the immune system and beyond. The heterozygous dominant gain-of-function patient proteins impaired chemokine signaling and chemotaxis in addition to augmenting T cell activation by constitutively activating costimulatory pathways and reducing the requirement for T cell costimulation. I also identified homozygous missense mutations in IFIH1, the gene encoding the cytosolic pattern recognition receptor of dsRNA MDA5, in the third family of study. The affected individual presented with recurrent severe respiratory infections with RNA viruses including human rhinovirus, coronaviruses (HKU1, OC43, NL63), influenza virus, and respiratory syncytial virus. The mutant protein lost the ability to bind dsRNA and failed to initiate antiviral interferon-β and pro-inflammatory NF-κB responses. Using gene knockdown and gene editing in immortalized and patient derived cell lines, I demonstrated an essential role for MDA5 in restricting rhinovirus infection in human respiratory epithelium. Thus this work demonstrates the power of human genetics to identify disease causing mutations in rare individuals and reveal how the immune system uses molecules involved in cell migration, activation, and nucleic acid sensing to robustly protect us from virus infections without causing autoimmunity. Degree Type Dissertation Degree Name Doctor of Philosophy (PhD) Graduate Group Immunology First Advisor Helen C. Su This dissertation is available at ScholarlyCommons: https://repository.upenn. edu/edissertations/2410 Second Advisor Michael J. Lenardo
Effect of energy and undegraded intake protein on growth and feed efficiency of growing Holstein heifers

Thirty-two Holstein heifers were used to determine the effect of energy and undegraded intake protein (UIP) on growth and feed efficiency from 6 mo of age until calving. Treatment diets were randomly assigned to one of four groups of eight Holstein heifers between 138 and 250 d of age (average of 180). Treatments were in a 2x2 factorial arrangement, consisting of two levels of energy (supporting.6 or .9 kg ADG) and two levels ofUIP (30 or 50% of CP). Heifers were fed treatment diets in a confinement facility until 385 d of age, constituting phase I of the trial. Isonitrogenous diets based on com silage, alfalfa silage, ground orchardgrass hay, shelled com, soybean meaL blood meal, and minerals were fed as a TMR. High VIP was achieved by substitution of blood meal for soybean meal. Phase IT began at the end of phase I and continued until calving. During phase ll, heifers were housed together and fed a common diet to achieve. 7 kg ADG. DMI (kg/d) for phase I was 4.46,5.42, 7.38, and 5.95 for Low Energy:Low VIP, Low Energy:High VIP, High Energy:Low VIP, and High Energy:High DIP. ADG (kg) was . 62, . 74, 1.01, and . 96. Feed efficiencies were 8.12, 7.58, 7.44, and 6.43 kg DMIlkg
The role of endogenous FeLV in the infectivity and genomic stability of FeLV subgroup A

Feline leukemia viruses (FeLV) are naturally occurring simple retroviruses associated with certain cancers, and are used as an important model system for studying the carcinogenic mechanisms of retroviruses. Of the three FeLV subgroups A, B and C, FeLV-B viruses are generated de novo from recombination between FeLV-A and endogenous FeLV (enFeLV). In a previous study investigating the pathogenicity of two FeLV-A molecular clones, pF6A and pFRA, FRA was found to be more pathogenic and recombinogenic than F6A. The goal of this dissertation was to extend our understanding of the factors contributing to FeLV recombination by evaluating the host cell/virus interactions of pFRA and pF6A. In addition, we investigated the expression of enFeLV RNA in feline tissues and cell lines and its role in the genetic instability of pFRA tagged to GFP gene in vivo and in vitro as a necessary step toward understanding the recombination process. FRA and F6A were equally infectious to feline fibroblast (FEA) and feline lymphoid (3201) cell lines. However, FRA was more recombinogenic than F6A in 3201 cells, although no difference in recombination potential between F6A and FRA was observed in FEA cells. These results indicate that the recombinogenic variation between F6A and FRA was cell-dependent. The probable mechanism for the increased recombinogenic potential of FRA in the 3201 cells was traced to the higher quantity of