Miracle-dz/UniFAR-FTUs huggingface dataset:
Human ß-defensin 2 is up-regulated during re-epithelialization of the cornea

Purpose. Human ß-defensins 1 and 2 (hBD-1, -2) are antimicrobial peptides found in several epithelia including corneal epithelium. Breach of the epithelium leaves the cornea vulnerable to infection so we sought to determine if there is an increase in defensin expression after injury. Methods. The epithelium from human cadaver corneas was collected by scraping (original samples). The corneas were then placed into organ culture to permit regeneration of the epithelium. Samples of re-grown epithelium were collected when healing was partially and 100% complete as determined by fluorescein staining. Total RNA was extracted from original and re-grown samples and used in RT-PCR reactions using primers specific for hBD-1 and hBD-2 and the constitutively expressed gene glyceraldehyde-3-phosphate dehydrogenase. Immunoblotting was performed to detect defensin peptide in original and re-grown samples. Results. hBD-1 mRNA was detected in all original epithelial tissue samples (n = 10) examined suggesting that it is constitutively expressed. hBD-2 mRNA was detectable in only two of the ten samples. Of six corneas placed in to organ culture, hBD-1 mRNA expression was unchanged in the re-grown epithelial samples compared to the original epithelium samples, however the expression of hBD-2 mRNA was markedly increased. hBD-1 and hBD-2 peptides showed the same pattern of expression as their respective transcripts. Conclusions. These data show that hBD-2 mRNA and peptide is up-regulated in the corneal epithelium during re-epithelialization which is in keeping with the role of this defensin as an antimicrobial peptide.
Transcriptional Regulation of Type I Diabetes by NF-κB 1

Development of type I diabetes requires coordinated expression of myriad genes responsible for the initiation and progression of the disease. Expression of these genes are regulated by a small number of transcription factors including the Rel/NF-κB family. To determine the roles of the Rel/NF-κB family in type I diabetes, we studied multiple low-dose streptozotocin-induced diabetes in mice deficient in either c-Rel or NF-κB1. We found that mice deficient in each of these NF-κB subunits were resistant to streptozotocin-induced diabetes. However, the mechanisms of the disease resistance may differ in different cases. Deficiency in c-Rel selectively reduced Th1, but not Th2 responses, whereas NF-κB1 deficiency had little effect on T cell responses to anti-CD3 stimulation. Death of dendritic cells was accelerated in the absence of NF-κB1, whereas death of macrophages and granulocytes was affected primarily by c-Rel deficiency. Furthermore, Stat-1 expression was significantly reduced in macrophages deficient in NF-κB1, but not c-Rel. These results indicate that both c-Rel and NF-κB1are essential for the development of type I diabetes and that strategies targeting each of these subunits would be effective in preventing the disease.
Evolution of terrestrial birds in three continents: biogeography and parallel radiations

Aim To reconstruct the biogeographical history of a large clade of mainly terrestrially adapted birds (coraciiform and piciform birds, owls, diurnal raptors, New World vultures, trogons, mousebirds, cuckoo‐rollers, seriemas, parrots and passerines) to test the hypothesis of its Gondwanan origin.
Sympathetic ganglia formation in the chick peripheral nervous system

The neural crest is a unique population of pluripotent cells that are crucial in vertebrate embryogenesis. In the trunk, NCCs migrate along a ventromedial pathway give rise to the dorsal root ganglia or the sympathetic ganglia (SG), or follow a dorsolateral pathway and give rise to melanocytes. Intriguingly, NCCs following the ventromedial pathway migrate in a metameric pattern through the rostral half somite and avoid the caudal somite and this is thought to dictate the metameric pattern of the SG. Static analyses have characterized the development of these structures, but timelapse imaging of NCCs in their normal environment could potentially reveal unidentified cellular and molecular interactions integral to SG development. However, because NCCs migrate deep within the embryo, it is challenging to track NCCs little is known about the cellular mechanisms mediating their migration, aggregation and differentiation. Here, we follow fluorescently labeled trunk NCCs using a novel sagittal explant culture system and timelapse confocal microscopy. We show trunk NCCs migrate in chain-like formations, and restriction to the rostral somite is not maintained once these cells arrive at the dorsal aorta. Instead, discrete SG only arise after an intermixing of cells along the ventral border of the somite followed by segregation into ganglia. The diverse cell migratory behaviors and active reorganization at the target sites suggest that cell-cell and cell-environment interactions are coordinated with dynamic molecular processes. In a screen for molecules expressed on NCCs during SG formation, we identified the cell adhesion molecule N-cadherin expressed once NCCs arrive adjacent to the dorsal aorta and form ganglia. Additionally, altering cadherin function drastically alters ganglia size. Additionally, we found EphrinB1 expression was absent adjacent to the dorsal aorta as NCCs had dispersed in this corridor, but strikingly up-regulated in the inter-ganglionic regions after discrete ganglia formation. The ephrinB1 receptor, EphB2, is also expressed on NCCs distributed adjacent to the dorsal aorta when discrete ganglia form. Altering ephrinB1/EphB2 signaling interferes with formation of the primary SG chain and blocks the formation of discrete ganglia. Taken together, these results indicate the importance of adhesive and inhibitory mechanisms in the formation of SG.
RIBBED MUSSEL NITROGEN ISOTOPE SIGNATURES REFLECT NITROGEN SOURCES IN COASTAL SALT MARSHES

The stable nitrogen isotope ratio in tissue of the ribbed mussel (Geukensia demissa) was investigated as an indicator of the source of nitrogen inputs to coastal salt marshes. Initially, mussels were fed a diet of 15N-enriched algae in the laboratory to determine how the tissue nitrogen isotope ratio (δ15N) changed with time. Steady-state times were calculated and found to be size dependent, ranging from 206 to 397 d. This indicated that mussels are long-term integrators of δ15N from their diet and may reflect nitrogen inputs to a marsh. Next, indigenous mussels were collected from 10 marshes with similar hydrology and geomorphology in Narragansett Bay, Rhode Island, USA, and mussel δ15N values were evaluated as indicators of nitrogen source. Significant positive correlations were observed between δ15N in mussels and the fraction of residential development in the marsh watersheds. In contrast, mussel isotope ratios showed significant negative correlations with the fraction of combined agricultural and recreational land use. These correlations suggested that the mussel nitrogen isotope signature is influenced by nitrogen derived from human activities in the adjoining marsh watershed. A more detailed examination of these relationships indicated that land use practices in close proximity to marshes and estuarine characteristics may also influence the observed nitrogen isotope signature. A simple, empirical model based on the 10 watersheds was developed to predict mussel δ15N from land use characteristics. The predictive ability of the model was tested with data from 12 additional marshes having similar geomorphology as the original 10, but differing in hydrology and mode of nutrient input. The model showed that ribbed mussel nitrogen isotope signatures may provide information on the source of nitrogen to coastal areas. This could be of use in developing general policies or strategies for monitoring and assessing coastal eutrophication. In addition, the isotopic ratio of mussels is useful as a proxy for watershed land use practices when assessing ecological responses to nutrient enrichment in coastal marshes.
Electric organ discharge variability of Mormyridae (Teleostei: Osteoglossomorpha) in the Upper Volta system

The electric organ discharges (EODs) of five mormyrid species (Marcusenius senegalensis, Brevimyrus niger, Petrocephalus bovei, Pollimyrus isidori, Hippopotamyrus pictus) from different sampling sites from the Upper Volta system in West Africa were investigated. EOD waveforms were recorded at high sampling rates in order to compare signal waveform parameters of the different species from different locations. Except for H. pictus, EODs within a species differed significantly from one another in some parameters and waveform variability at least between some sampling sites. In addition, each species showed a continuous spectrum of waveform variations, all or only parts of which were found at certain localities. Although there was variability and sometimes similarities between species, the EOD waveforms were species specific. Knowing their variation spectrum, they can be used for species determination and are probably used for species recognition by the mormyrids. Similarities or differences in EOD waveform expression within a species were not related to geographical distance. By contrast, we suggest that biotic environmental factors at a given location influence the expression of EOD waveforms. These factors affect absolute measurements such as EOD duration and fast Fourier transformation peak frequency as well as the amount of variation for certain waveform parameters across species in a similar manner for a given site. Although EOD waveform might be important for the establishment of reproductive barriers between species, our results suggest that differences in waveforms may not necessarily reflect different species or speciation processes in progress.
THE REGULATION OF DENRITIC CELL FUNCTION IN AUTOIMMUNE PRONE AND WILD TYPE MICE

Dendritic cells (DCs) represent a heterogeneous set of antigen presenting cells linking the innate and adaptive immune systems. DCs are referred to as professional antigen presenting cells (APCs) with regards to their ability to activate naive T cells. In this study, the role that DCs play in the pathogenesis of Type 1 Diabetes (T1D) was initially examined. We utilized an experimental model that allowed for the generation of bone marrow derived-dendritic cells (BM-DC) subsets that exhibit either a DC type 1 (DC1) or DC2 phenotype. We define DC1 as cells capable of producing high levels of IL-12 and inducing naive CD4+ T cell differentiation into T helper 1 (Th1) cells while DC2 are cells that produce low levels of IL-12 and induce Th2 cell differentiation. During the course of this study we also utilized several toll-like receptor (TLR) ligands to activate DC function. In addition, we tracked the migration of DCs in vivo utilizing a novel perfluoropolyether (PFPE) contrasting agent in conjunction with a modified magnetic resonance imaging (MRI) instrument. With this methodology we tested the hypothesis that NOD DCs were predisposed to adopt a DC1 phenotype that contributed to the pathogenesis of T1D. The results from our experiments show that NOD BM-DCs induced into a DC1 or DC2 functional phenotype exhibit no significant intrinsic differences in their production of IL-10 or IL-12, in comparison to wild type mice. Additionally, NOD BM-DCs expressed similar levels of CD80, CD86, CD40, and MHC class II in comparison to wild type BM-DC. Our analysis did show that the production by BM-DCs of IL-10, induced by CpG ODN, is negatively regulated by IFN-gamma. The suppressed production of IL-10 may have implications for the development of T helper cell type 1 (Th1) and Th2 cells. Altogether our study has shown that, 1) NOD BM-DCs are not intrinsically skewed towards a DC1 phenotype, 2) IFN-gamma negatively regulates the production of IL-10 in BM-DCs, and 3) NOD BM-DCs can be successfully imaged in vivo using a novel PFPE labeling/MRI detection technique.
Impact of entomopathogenic nematodes on adults of Phyllotreta spp. (Coleoptera: Chrysomelidae) under laboratory conditions

Abstract In 2005, preparations of four species of the entomopathogenic nematodes Steinernema feltiae, S. carpocapsae, Heterorhabditis bacteriophora, and H. megidis, were tested under laboratory conditions for their ability to kill adult flea beetles, Phyllotreta spp. (Coleoptera: Chrysomelidae). The nematode preparations were tested at doses of 200, 1000, and 2000 IJs per adult and at temperatures 15°C, 20°C, and 25°C. The numbers of beetles killed were recorded two, four, six, and eight days after treatment. The nematodes were more effective at 20°C and 25°C than at 15°C. At 20°C, the nematodes had killed between 44% (H. megidis at the lowest dose tested) and 77% (S. feltiae at the lowest dose tested) of the beetles eight days after treatment. At the two highest doses tested, the S. feltiae, S. carpocapsae, and H. bacteriophora preparations each killed at least 74% of the beetles at 25°C. Steinernema feltiae was the most effective nematode (LC50=483–1467 IJs/adult) and, as an alternative to chemical insecticides, appears to have the highest potential for controlling overwintered flea beetles (May) under field conditions. The nematodes S. feltiae, S. carpocapsae and H. bacteriophora would all be suitable for controlling adult flea beetles during warm summer months, when flea beetles occur in high numbers in Slovenia.
Antimicrobial Resistance Patterns of Isolated Vibrio cholerae Strains

Background: Cholera is a potentially life-threatening acute diarrheal disease caused by the toxigenic bacteria, Vibrio cholerae. Antibiotics should be selected using local antibiotic susceptibility testing patterns. Objectives: This study was performed to identify the patterns of antimicrobial resistance in isolates collected from laboratory-confirmed cases of cholera during three years, from 2011 to 2013. Materials and Methods: All isolates at the Health Reference Laboratory were tested by the Minimum Inhibitory Concentration (MIC) Test using Liofilchem against ciprofloxacin, nalidixic acid, cefixime, ampicillin, tetracycline, trimethoprim-sulfamethoxazole, and erythromycin. The following organisms were used as quality control strains for MIC E-testing; Escherichia coli (ATCC 25922), Staphylococcus aureus (ATCC 29213), and Pseudomonas aeruginosa (ATCC 27853). Results: Results of susceptibility testing showed complete sensitivity to ciprofloxacin, cefixime and amplicillin for both isolated Inaba and Ogawa serotypes except all isolated Inaba serotypes from year 2011, which were resistant to cefixime. These resistant Inaba serotypes were not isolated in the next year. Inaba serotypes showed an increased resistance rate of up to 100% to nalidixic acid, tetracycline and trimethoprim-sulfamethaxazone, while Ogawa serotypes were 100% sensitive at the end of year 2013. The susceptibility pattern of erytromycine was similar in these two types. Sensitivity to erythromycin was decreased in both Inaba and Ogawa serotypes. Conclusions: The analyzed results indicate that tetracycline should not be considered as a first line antibiotic therapy for patients infected with Ogawa serotypes. Also, national guidelines for confirmation of cholera should be improved by responsible authorities to cover new resistance during outbreaks.
Small molecule inhibitors of Mdm2 E3 ubiquitin ligase activity

Half of cancers retain wild type p53 but have alterations in the pathways involved in p53 regulation. Murine double minute 2 (Mdm2) regulates p53 by acting as an E3 ubiquitin ligase, which tags p53 for degradation through the proteasome. A small molecule inhibitor, a 5-deazaflavin analogue, has previously been identified by high throughput screening to inhibit Mdm2 E3 ubiquitin ligase activity, thereby reactivating apoptotic function of p53 selectively in cancer cells. Ninety 5-deazaflavin analogues have been synthesised by an optimized existing method and a novel method of synthesis, using the required 6-anilinouracil and 2-p-toluenesulfonyloxybenzaldehyde.The biological ability of the 5-deazaflavin analogues to act as inhibitors of Mdm2 E3 ubiquitin ligase activity to reactivate p53 has been ascertained. A new quantitative biological assay was developed, by scientists based at the Beatson Institute, for 5-deazaflavin compounds, showing excellent inhibition of Mdm2 E3 ubiquitin ligase activity on the previous qualitative biological assay, to yield IC50 data. The biological results have established a clear and logical structure-activity relationship comprising of an electron-withdrawing hydrophobic substituent at the nine position and the N10 phenyl being a prerequisite for activity as a Mdm2 inhibitor. Also meta substitution of the N10 phenyl improves activity against Mdm2 E3 ubiquitin ligase activity. Hit optimization has occurred with 10-(3-chlorophenyl)-9-trifluoromethyl-5-deazaflavin being thirty times more active than the previous identified hit compound, 10-(4-chlorophenyl)-7-nitro-5-deazaflavin. Using the X-ray crystal structure of the Mdm2/MdmX heterodimer, an improved understanding of how Mdm2 acts as an E3 ubiquitin ligase is described and used to form a hypothesis of how 5-deazaflavin analogues function as inhibitors of Mdm2. The work suggests the principle that small molecular weight compounds can inhibit E3 ubiquitin ligases as a possible anti-cancer therapy, and provide the foundation and framework for additional studies and investigation in a new and developing field of medicinal chemistry.
Aggregation and Coexistence in a Carrion Fly Community

In this paper I combine experiment and theory to demonstrate that aggregation of carrion flies ovipositing among carcasses may facilitate coexistence in nature. The paper is divided into an experimental part and a theoretical part. In the experiment part, I present field experiments that show the aggregative pattern of carrion flies ovipositing among carcasses, as well as associated experiments that explore the behavior leading to these patterns. I also use experiments to quantify the strength of larval competition between Phaenicia coeruleiviridis (Calliphoridae) and Sarcophaga bullata (Sarcophagidae). In the theoretical part, I develop two methods that use these data to assess the effect of aggregation on competition in the field. From the first method, I predict that intraspecific aggregation of P. coeruleiviridis females causes a 26% decrease in the expected recruitment of P. coeruleiviridis and a 74% increase in the expected recruitment of S. bullata. As a result, within a single generation, intraspecific aggregation increases intraspecific competition and reduces interspecific competition. The second method for assessing aggregation involves a new mathematical formula that gives conditions under which species may coexist indefinitely. This formula requires estimates of only the degrees of intra— and interspecific aggregation among species; there is no need to estimate adult survival and larval competition. I use this second method to show that the minimum effect of aggregation on coexistence for five carrion fly species is equivalent to reducing the amount of larval competition between pairs of species by an average of 57%. Aggregation may therefore play a major role in explaining the coexistence of carrion fly competitors.
Interactions between land use/land cover change, forest fires and landscape structure in Sierra de Gredos (Central Spain)

In fire-prone areas, like the Mediterranean, land abandonment and forestation may interact with fire to alter landscape properties and eventually fire hazard and occurrence. However, the spatial interactions among the two processes (land-use/land cover change [LULC] and fire) are poorly known. Here, we analysed the relative effect of LULC change and fire on the landscape structure of an area of Central Spain frequently affected by fire. A series of Landsat MSS images from 1975 to 1990 was analysed to quantify annual changes in LULC, map fire perimeters and evaluate the changes in landscape properties. The temporal dynamics were analysed by annually computing the fraction occupied by each LULC type and landscape structural properties (number, size, shape and arrangement of patches) that might play a role in fire propagation. All of these were calculated separately for the unburned or the burned areas during the study period, as well as for the entire area. At the whole landscape level, or in the unburned area, LULC changes were small, yet the two more flammable LULC types tended to increase, and the landscape tended to become more homogeneous. In the burned area, the area covered by pine woodlands tended to decrease, and that covered by shrublands to increase. Burned areas turned into shrublands only five years after fire. Landscape indices indicative of reduced fragmentation were also found. Both LULC change and fire altered landscape patterns in the whole area to create a less fragmented and more contiguous landscape than in 1975. The changes induced in the whole landscape by fire, in spite of the overall low disturbance rate, were sufficient to closely determine the changes in landscape composition (LULC types) and patterns.
Acidity is one of the main mechanism for hypoxia triggering chemoresistance to mitoxanthrone (MX) in the human breast cancer MCF-7 cell line

Breast cancer, the most frequently diagnosed cancer and the leading cause of cancer-related deaths in women worldwide, accounts for 23% of the total cancer cases and 14% of cancer deaths [1]. According to a cancer registration report from the Taiwan Ministry of Health and Welfare (MOHW), the incidence rate for breast cancer was the highest for any cancer, with 33 women being diagnosed with the disease and 5.67 women dying from it on a daily basis [2]. Although breast cancer is responsive to a wide array of single and combination chemotherapy regimens, some initially responsive breast cancer patients may relapse and develop resistance to multiple anticancer agents with different structures and mechanisms of action, leading to metastases and eventual death from the disease [3]. As such, insights at the cellular and molecular levels may broaden our understanding of the development of chemoresistance and hold therapeutic promise against the cancer. The development of multidrug resistance (MDR) and subsequent relapse when receiving therapy is a widespread problem in patients with breast cancer [4]. MDR is caused by multidrug transporters (MDTs), which can recognize a wide variety of chemical substrates and pump them out of cells to reduce intracellular levels of the substrates, thereby causing treatment failure [5]. MDTs, which are also called ATP-binding cassette transporters (ABC-transporters), utilize the energy of adenosine triphosphate (ATP) hydrolysis to conduct biological reactions [6]. The P glycoprotein (Pgp) and the multidrug resistance-related protein (MRP) are two typical ABC transporters and have been found to be overexpressed in breast cancer cells [7, 8]. Meanwhile, the discovery of ATP-binding cassette sub-family G member 2 (ABCG2) has explained the puzzle of non-Pgp and non-MRP-mediated mechanisms seen in some tumors [9]. ABCG2 is expressed in several kinds of tumors, including breast cancer, gastric carcinoma, hepatocellular carcinoma, endometrial carcinoma, colon cancer, small cell lung cancer, and melanoma [10], and is associated with resistance due to its active extrusion of diverse therapeutic com-