Miracle-dz/UniFAR-FTUs huggingface dataset:
Validation and application of Caco-2 assays for the in vitro evaluation of development candidate drugs as substrates or inhibitors of P-glycoprotein to support regulatory submissions

1. An understanding of the role that transporters, in particular P-glycoprotein (P-gp), can play in the absorption, distribution, metabolism and excretion (ADME) of candidate drugs, and an assessment of how these processes might impact on toxicity and the potential for drug–drug interactions in the clinic, is required to support drug development and registration. It is therefore necessary to validate preclinical assays for the in vitro evaluation of candidate drugs as substrates or inhibitors of human P-gp. 2. The present study has characterized a Caco-2 cell monolayer model by determining the bi-directional apparent permeabilities and efflux ratios of the known P-gp substrates ([3H]-digoxin, [3H]-ketoconazole, [3H]-verapamil, [3H]-quinidine, dipyridamole and loratidine; 1–100 µM) a non-substrate ([3H]-propranolol; 10 µM), or by determining the inhibitory potencies (IC50) of inhibitors (verapamil, ketoconazole, quinidine, dipyridamole and probenecid; 0.1–100 µM) on the basolateral-to-apical transport of [3H]-digoxin (5 µM), in order to validate methodologies for the identification of substrates or inhibitors of P-gp, respectively. 3. The reproducibility of the [3H]-digoxin or verapamil data determined from replicate monolayers across different cell passages indicates that the functional expression of P-gp is consistent across the range of passages (25–40) utilized for transport experiments and that the determination of bi-directional apparent permeability, or IC50 for inhibition of P-gp, respectively, need only be performed on one occasion for a test compound. [3H]-digoxin and [3H]-propranolol or verapamil and probenecid were considered to be appropriate positive and negative controls of P-gp-mediated transport, or inhibition of P-gp, respectively, to ensure performance of the assays when assessing candidate drugs. Additionally, the low IC50 values determined for ketoconazole and quinidine indicated that these inhibitors were suitable to use to confirm the role of P-gp in the efflux of a test compound. 4. These validated Caco-2 assays are robust, reproducible and suitable for routine in vitro evaluation of candidate drugs. They have been successfully applied to development projects resulting in the identification of two candidate drugs as substrates and inhibitors of P-gp, whereas a third was neither a substrate nor an inhibitor of this transporter.
Environmental determinants of Phragmites australis expansion in a New Jersey salt marsh : an experimental approach

Interdependence among disturbance events, ecosystem properties, and biological invasions often make causal relationships difficult to discern. For example, Phragmites australis invasion in mid-Atlantic salt marshes is often associated with disturbances that create well-drained features as well as with low sulfide concentrations, but explanations of these associations have been elusive. We tested experimentally: 1) that disturbances increasing wetland drainage facilitate Phragmites invasion by altering sulfide concentrations and salinity; 2) that translocation allows plants to spread beyond drainage areas; and 3) that plants can then lower edaphic stress through pressure ventilation of the rhizosphere and promote further expansion. At the invasion front, treatments of 1) severing rhizomes to halt translocation and 2) combined severing with clipping dead culms to limit ventilation of the rhizosphere killed most culms, but did not affect pore water chemistry. In already invaded areas, severing and clipping reduced culm height and panicle production, severing alone and in combination with clipping also raised sulfide and ammonium concentrations in the root zone. There were no treatment effects on plant performance or pore water chemistry along mosquito ditches, where sulfide concentrations were negligible. Small-scale hydrological alterations such as ditches appear to provide suitable sites for the establishment of Phragmites because soils are well-drained and are low in free sulfides. Subsequent expansion into more hostile areas occurs through translocation, with well-drained areas acting as sources for essential substances. Once established, the plant increases rhizosphere oxygenation and lowers sulfide concentrations.
Collision risk and micro-avoidance rates of birds with wind turbines in Flanders

Capsule Local factors can lead to strong variation in mortality rate and collision risk that obscures possible effects of turbine size in wind farms. Aims The impact of bird collisions was studied at eight land-based wind farm sites with a total of 66 small to large turbines in order to assess the mortality rate and collision risk. Methods Searches for collision fatalities were performed under all turbines with a minimum search interval of 14 days. Mortality rate was calculated with corrections for available search area, scavenging and search efficiency. Flight movements of birds crossing five of the wind farm sites were recorded during a minimum of four days per site. Actual collision risk was then calculated as the number of collision fatalities relative to the average surveyed flight intensity. Results Mortality rate was 21 birds per turbine per year on average. Most fatalities were local common species (e.g. gulls) but rarer species were also found (e.g. terns, raptors and waders). Collision risk of gulls was 0.05% and 0.08% on average for birds, respectively, flying at turbine and rotor height through the wind farms (0.09% and 0.14% maximum). Large gulls had a significant higher collision risk than small gulls at rotor height. Mortality rate and collision risk were not significantly related to turbine size. The results were integrated in a widely used collision risk model to obtain information of micro-avoidance, i.e. the proportion of birds that fly through the wind farm but avoid passing through the rotor swept area of the turbines. For gulls, this micro-avoidance was 96.1% and 96.3% on average for birds, respectively, flying at turbine and rotor height through the wind farms. Conclusion The results indicate that local factors can lead to strong variation in mortality rate and collision risk that obscures possible effects of turbine size in wind farms. However, large turbines have more installed capacity (MW), so repowering wind farms with larger but fewer wind turbines, could reduce total mortality at certain locations.
The taphonomy of colour in fossil insects and feathers

Colouration is an important multifunctional attribute of modern animals, but its evolutionary history is poorly resolved, in part because of our limited ability to recognize and interpret fossil evidence of colour. Recent studies on structural and pigmentary colours in fossil insects and feathers have illuminated important aspects of the anatomy, taphonomy, evolution and function of colour in these fossils. An understanding of the taphonomic factors that control the preservation of colour is key to assessing the fidelity with which original colours are preserved and can constrain interpretations of the visual appearance of fossil insects and theropods. Various analytical approaches can identify anatomical and chemical evidence of colour in fossils; experimental taphonomic studies inform on how colour alters during diagenesis. Preservation of colour is controlled by a suite of factors, the most important of which relate to the diagenetic history of the host sediment, that is, maximum burial temperatures and fluid flow, and subsurface weathering. Future studies focussing on key morphological and chemical aspects of colour preservation relating to cuticular pigments in insects and keratinous structures and nonmelanin pigments in feathers, for example, will resolve outstanding questions regarding the taphonomy of colour and will enhance our ability to infer original colouration and its functions in fossil insects and theropods.
Ultimate functions of non-fruiting flowers in Lathyrus vernus

In this study, four hypotheses concerning female function of non-fruiting flowers in a herbaceous perennial legume, Lathyrus vernus, were examined. I found no evidence that surplus flowers serve to increase the opportunities for maternal selection based on offspring quality, or to decrease seed predation by dispersing oviposition of seed predators. However, a proportion of the cost of surplus flowers may be counterbalanced by gains from increased pollinator attraction and increased fruit set in years with low pollen availability. Furthermore, surplus distal flowers function as reserveovaries if basal flowers are preyed upon or not fertilized. A quantitative model based on the reserve-ovary function predicted half of the surplus flowers actually observed. This study thus suggests that surplus flowers in L. vernus serve several functions simultaneously.
Short communication Genetic diversity of an endangered aquatic plant, Potamogeton lucens subspecies sinicus

The genetic diversity of the species, Potamogeton lucens subsp. sinicus var. teganumensis, which is critically endangered in Japan, was investigated. This species now occurs in only two known localities in Japan. One is a native population (Oitoike population), but the other (Teganuma-Okahotto population) is found in a small artificial pond that was dug in 1998. It is considered that the Teganuma-Okahotto population grew from a soil seed bank. Based on RAPD variation, we compared the genetic diversity of the two populations of P. lucens var. teganumensis in Japan and one populationofP.lucenssubsp. sinicusvar. sinicusinChina.The Teganuma-Okahottopopulation showed RAPD variation, suggesting that it may be derived from more than one seed buried in old sediments. This population also had the highest value of Shannon’s Information Index amongthethreestudypopulations.Thisfindingsuggeststhatseedsburiedinsedimentscancontaingeneticvariability,andmaybeusedtoconserve
Appl. Entomol. Zool. 42 (4): 557–562 (2007)

The effect of a commercial formulation of Bacillus thuringiensis (Dipel 2X) upon F1 progeny of irradiated and nonirradiated Phthorimaea operculella male parents was investigated. F1 progeny of irradiated parents was more susceptible to B. thuringiensis than that of nonirradiated parents. A combination of irradiation and B. thuringiensis led to higher mortality in F1 progeny of P. operculella. The LC50 was 0.406 g/100 ml for F1 progeny of nonirradiated parents, but 0.199 g/100 ml for those of irradiated parents. There was a great reduction in the pupal weight, fecundity and egg hatchability of F1 progeny of irradiated parents compared to nonirradiated parents. Such reduction was increased by applying a higher concentration of B. thuringiensis. A combination of the inherited sterility technique and B. thuringiensis application gave a good control result against P. operculella.
Simplified rotational grazing management of dairy cows: effects of rates of stocking and concentrate

SUMMARY An experiment was carried out in Normandy between 1986 and 1988 over c. 6 months in each year, using a simplified rotational grazing technique (two paddocks in spring, four in autumn) with a total of 162 high-yielding cows (mean milk yield of 30·0 kg/day at turn-out). Three stocking rates, designated control (C: 2·3 cows/ha over the total area of the system), moderate (M: 2·6 cows/ha = 115% of C) and high (H: 3·0 cows/ha = 130% of C), were compared at two rates of concentrate supplement, 3·7 kg/cow per day and 0·5 kg/cow per day. Individual milk yield differed by a non-significant 5% between the extreme stocking rates (21·3 v. 20·3 kg fat-corrected milk (FCM) for treatments C and H, respectively). Milk production/ha was 23% greater in the H treatment (9816 v. 7970 kg FCM for H and C, respectively). Concentrate supplementation led, on average, to a 9% milk yield improvement (21·8 v. 20·0 kg FCM for high and low rates, respectively), i.e. a mean efficiency of 0·6 kg FCM/kg supplement. This response tended to be greater in the higher-yielding cows and for the high stocking rate. The sward measurements contributed to a better understanding of herbage utilization by the cows.
RIP2 Is a Novel NF-κB-activating and Cell Death-inducing Kinase*

Through specific interactions with members of the tumor necrosis receptor (TNFR) family, adapter molecules such as the serine/threonine (Ser/Thr) kinase RIP mediate divergent signaling pathways including NF-κB activation and cell death. In this study, we have identified and characterized a novel 61-kDa protein kinase related to RIP that is a component of both the TNFR-1 and the CD40 signaling complexes. Receptor interactingprotein-2 (RIP2) contains an N-terminal domain with homology to Ser/Thr kinases and a C-terminal caspaseactivation and recruitment domain (CARD), a homophilic interaction motif that mediates the recruitment of caspase death proteases. Overexpression of RIP2 signaled both NF-κB activation and cell death. Mutational analysis revealed the pro-apoptotic function of RIP2 to be restricted to its C-terminal CARD domain, whereas the intact molecule was necessary for NF-κB activation. RIP2 interacted with other members of the TNFR-1 signaling complex, including inhibitor of apoptosis protein cIAP1 and with members of the TNFR-associated factor (TRAF) family, specifically TRAF1, TRAF5, and TRAF6, but not with TRAF2, TRAF3, or TRAF4. These TRAF interactions mediate the recruitment of RIP2 to receptor signaling complexes.
The decline of elephant and black rhinoceros in Ethiopia

From the authors' review of the mammals of Ethiopia, undertaken during the last 14 years, it is clear that Ethiopia's elephants and rhinoceroses have suffered massive declines since the beginning of the century. There are perhaps 9000 elephants left, but poaching for ivory and agricultural encroachment continue to threaten them, and only a few rhinoceroses still survive. Ethiopia has limited resources to protect these remaining animals, and needs help and encouragement from outside its boundaries.
Die Triterpenoide der Birnen‐ und Apfelschale

Neben schon von anderen Rosaceen her bekannten Triterpensäuren wird aus den Schalen von Birne und Apfel erstmals 3β,19α‐Dihydroxyursa‐12‐en‐2‐on‐17‐säure isoliert. Sie erhält den Namen Pirolonsäure (4).
Multiple Laying by the Silver Gull, Larus novaehollandiae Stephens, on Carnac Island, Western Australia

In 1977 and 1978, silver gulls on Carnac I. , near Perth, W.A. , bred continuously from March to November, with laying peaks in April, June and August-September. Many pairs laid several times during the year, showing complex patterns of replacement and post-refractory clutches. This prolonged breeding appears to have resulted from sustained predation pressure in an environment with few climatic or food constraints. Intra-clutch egg variation and seasonal changes in clutch and egg sizes followed the patterns common among gulls. Egg sizes in clutches laid by the same individual were very similar, irrespective of time of year.
Environmental microbe and human pathogen: the ecology and microbiology of Vibrio cholerae

Vibrio cholerae, the bacterium that causes cholera, is a fascinating microorganism that occupies two distinct habitats: aquatic environments and human intestines. Although its activity in human hosts has received a great deal of attention because of its effect on human health, the microbe's behavior in natural ecosystems has received much less consideration. In this paper we briefly review the microbiology and ecology of V. cholerae, before highlighting four important areas for further research. First, V. cholerae acts as a typical heterotrophic bacterium while in aquatic environments, mineralizing organic matter for reuse within the food web. In addition, three key processes affect the microorganism's population dynamics and therefore its role in ecosystem processes: a viable-but-non-culturable (VBNC) state, attachment to environmental substrates, and bacterivory. Several factors link V. cholerae in its human and aquatic habitats, especially human activities that influence its growth conditions while out.
A Phase I/II Clinical Trial of β‐Globin Gene Therapy for β‐Thalassemia

Abstract: Recent success in the long‐term correction of mouse models of human β‐thalassemia and sickle cell anemia by lentiviral vectors and evidence of high gene transfer and expression in transduced human hematopoietic cells have led to a first clinical trial of gene therapy for the disease. A LentiGlobin vector containing a β‐globin gene (βA‐T87Q) that produces a hemoglobin (HbβA‐T87Q) that can be distinguished from normal hemoglobin will be used. The LentiGlobin vector is self‐inactivating and contains large elements of the β‐globin locus control region as well as chromatin insulators and other features that should prevent untoward events. The study will be done in Paris with Eliane Gluckman as the principal investigator and Philippe Leboulch as scientific director.
Exploring Component Stability Using Life‐Stage Concordance In Sabethine Mosquitoes (Diptera: Culicidae)

Abstract — Morphological characters from sabethine mosquitoes were coded from larvae, pupae and adults, and life‐stage partitions were evaluated to determine the contribution of each to the topology of a combined cladogram. Initial tests failed to find congruence between characters partitioned by life stage. However, when components from the combined analysis were tested using reduced taxon sets, a high degree of concordance between partitions was observed. A procedure for assessing individual life‐stage contribution is employed, in which exhaustive searches are used to explore all possible arrangements for each of the selected components. Seven of the 10 components examined were able to recover the combined topology with a reduced taxon set. Congruent arrangements of taxa were typically observed for two or more life stages, although partitioned data were less resolved and frequently included aberrant topologies (those not supported by other partitioned or combined reduced taxon tree sets). In addition, none of the partitioned data sets gave robust results for all tests, suggesting that studies which emphasize character data from single life stages may support misleading arrangements of taxa. One component on the combined cladogram was not supported by any of the life‐stage partitions when analysed separately. These results are complementary to “total evidence” approach, and demonstrate that partitions of data are useful for examining suits of characters which may cause some components of the “total
Morphological and cytological observations of wild species and hybrids of Gypsophila

Gypsophilapaniculata L. is among the 10 best selling cut flower species globally and is considered a “target” plant for breeding varieties. The aim of this work was to make the genetic improvement of Gypsophila more rational and focused. The study of basic chromosome number and the reproductive system (potential barriers to intraspecific and interspecific incompatibilities) of the wild species as well as the commercial hybrids forms the basis of crossbreeding and selection of variety. A significant difference in ploidy was found between the species paniculata, its cultivar Flocon de Neige doubles, the species libanotica Boiss. (n = 34) and Pacifica Kom. (n = 68). A significant difference in the chromosome number was found among the commercial hybrids of Gypsophila under investigation, and this difference was observed among them as well as when compared with the wild type species. The flower structure of commercial hybrids can be remarkably complex. Some hybrids such as Biancanieves® and MeryG® showed empty pollen sacs, whereas others such as “Mirabella” and New Love® showed pollen grains trapped into anthers. However, the pollen, when present, exhibits immature or degenerated appearance. The examined commercial hybrids showed a gynoecium morphologically and anatomically conforming to that of wild species and it was potentially fertile. Therefore, the fertile pollen collected from the wild species could be used to fertilize the compatible eggs of commercial hybrids, thereby speeding the process of breeding varieties.
Initiation and termination of DNA replication of plasmid pKYM via a rolling-circle mechanism.

The replication origin of plasmid pKYM, which replicates via a rolling-circle mechanism, is composed of three regions with the following characteristics. 1) The core origin, which is essential for initiation of DNA replication, consists of 39 base pairs. The purified Rep protein of pKYM (RepK) binds specifically to this 39-base-pair region. Within the 39-base-pair origin, there is a sequence of 22 base pairs that is sufficient for termination. 2) The initiation-enhancing region consists of a 98-base-pair region downstream of the core origin. A host protein(s) binds to this region in the presence of RepK. 3) A 34-base-pair sequence upstream of the core origin is essential for the multiplication of pKYM. Multimers of the plasmid DNA were produced in the absence of this region. The region may enhance correct processing of the unit length plasmid DNA. A host protein binds to this region
Mechanisms of the jaws of some atheriniform fish

The Atheriniformes is an order of teleost fish which consists of the Atherinoidei (sand smelts etc.), Cyprinodontoidei (tooth-carps) and Exocoetoidei (halfbeaks etc.). Some of its members have protrusible upper jaws and some do not. Photographs have been taken of two species of Cyprinodontoidei feeding, to discover how they use their jaws, which are protrusible. The anatomy and mechanisms of the jaws of these and of various other Atheriniformes have been studied. The terminology of the kinematics of machines is used in a general discussion of the mechanisms of teleost jaws. Anatomical similarities between the jaws of Acanthopterygii, Cyprinoidei and Atheriniformes are noted and discussed.
Profitability and technical efficiency of aquaculture in Punjab, India

The profitability and technical efficiency aspects of aquaculture in Punjab were examined using primary data pertaining to the year 2007-08 using cost and return concepts and stochastic frontier production function, respectively. Study showed that only two-fifth of the farms were using nursery ponds for fingerlings in early stages and few farmers were using branded feed. Application of chemical fertilisers and manures were directly and inversely related to farm size. Differences between observed and frontier output is attributed mainly to the inefficient use of resources which are under the control of fish farmers. Use of nursery, high proportion of rohu and training received by fish farmers were significantly affecting the technical efficiency. Aquaculture in Punjab is high yielding and profitable despite certain constraints. High cost of feed, low dissolved oxygen, poor availability of electricity, inadequate seed supply and poor quality of seed were perceived as the major constraints to aquaculture. The findings indicated that the farmers need to be trained for use of nursery ponds and optimum mix of resources to increase profitability in fish production. Further there is urgent need for development of low cost feed and establishment of more hatcheries to meet the demand of disease free and disease resistant fish/shrimp seed with strict quarantine measures.