Miracle-dz/UniFAR-FTUs huggingface dataset:
Whole body physiologically-based pharmacokinetic models: their use in clinical drug development

Background: Whole-body physiologically-based pharmacokinetic (WB-PBPK) models mathematically describe an organism as a closed circulatory system consisting of compartments that represent the organs important for compound absorption, distribution, metabolism and elimination. Objectives: To review the current state of WB-PBPK model use in the clinical phases of drug development. Methods: A qualitative description of the WB-PBPK model structure is included along with a review of the varying methods available for input parameterisation. Current and potential WB-PBPK model application in clinical development is discussed. Conclusions: This modelling tool is at present used for small and large molecule drug development primarily as a means to scale pharmacokinetics from animals to humans based on physiology. The pharmaceutical industry is active in employing these models to clinical drug development although the applications in use now are narrow in comparison to the potential. Expanded integration of WB-PBPK models into the drug development process will only be achieved with staff training, managerial will, success stories and regulatory agency openness.
A New Giant Salamander (Urodela, Pancryptobrancha) from the Miocene of Eastern Europe (Grytsiv, Ukraine)

ABSTRACT We present new and well-preserved giant salamander material from the Miocene of the Grytsiv locality, Ukraine. Disarticulated skull and postcranial bones from two individuals are described as a new taxon, Ukrainurus hypsognathus, gen. et sp. nov. U. hypsognathus is characterized by poorly ossified bone tissues, relatively inflexible mandibles, a high dentary, a crista on the lingual surface of the dentary, a pars dentalis of the dentary that is composed of a dental lamina and a subdental surface, presence of an eminentia dorsalis on the squamosal, a broad pericondylar facet on the occipital, extremely elongated prezygapophyses, and hemal processes with an elongate, oval base. Moreover, U. hypsognathus shows evidence of strong mandibular levator muscles that indicate great biting force. A phylogenetic analysis of all well-understood Tertiary and Recent giant salamanders recovers a monophyletic group of Asian and North American cryptobranchids, but places U. hypsognathus outside crown group Cryptobranchidae. This result suggests that Cryptobranchidae originated in Asia and dispersed to North America. The oldest representative of crown Cryptobranchidae is Aviturus exsecratus from the terminal Paleocene of the Nemegt Basin, Mongolia.
Physicochemical properties of cassava, potato and jicama starches oxidised with organic acids

an, Sin. , CP 80000, M ´ exico Abstract: The oxidising effects of organic (acetic, citric and lactic) acids on the physicochemical properties of starches from cassava, potato and jicama were investigated. Cassava starch oxidised with lactic and citric acids had the highest carbonyl contents (5.43 and 5.84gkg −1 respectively), while oxidised potato starch had the highest carboxyl contents. Oxidised jicama starch showed the lowest carbonyl and carboxyl contents. Oxidation increased the maximum viscosity of cassava starch (from 426.61 to 670.11 relative viscosity units (RVU)) and jicama starch (from 160.17 to 561.50 RVU) but decreased that of potato starch (from 669.44 to 206.92 RVU). When carbonyl and carboxyl groups were incorporated into jicama starch granules, the resistance of these granules to stirring at constant temperature (holding) increased, as did their final and retrogradation viscosities. However, the behaviour of oxidised cassava and potato starches, as indicated by a Rapid Visco Analyser, was different. The highest values of endotherm enlargement were found for native and oxidised jicama starch, while the lowest values were found for native and oxidised cassava starch. Native and oxidised potato starch had the highest enthalpy values (14.30-18.30Jg −1 ), while jicama starch had the lowest (9.50-11.9Jg −1 ). The high intrinsic viscosity of native potato starch was attributed to B-type starch with a longer-than-average amylopectin chain length and a lower degree of crystallinity. Oxidised granules showed little erosion in the form of grooves; on the contrary, oxidation left the grains with a very smooth surface.  2007 Society of Chemical Industry
Small RNA-mediated Gene Regulation in Caenorhabditis elegans

Small RNA-mediated gene silencing is an ancient, evolutionarily conserved and only recently discovered gene regulatory mechanism. This thesis is aimed towards understanding the function of small RNA pathways in the model organism Caenorhabditis elegans, and furthermore to understand their role in neurodegenerative diseases. In order to study small RNA pathways and their potential therapeutic applications in neurological diseases, molecular genetic, RNA interference, microarray, and in silico techniques were used as an experimental approach. Firstly, different neuron types were examined for their sensitivity to exogenously delivered small interfering RNAs (exo-siRNAs). The sensitivity was found to vary between different neuron types and dysfunctional RRF-3 protein was shown to increase the effectiveness in all measured cell types. Secondly, using an rrf-3 mutant animal, candidate targets of endogenous small interfering RNAs (endo-siRNAs) were identified and their functions were found to be enriched in regulating genes involved in protein phosphorylation, embryonic development, and sperm motility. Thirdly, endogenous siRNAs previously identified by high-throughput sequencing were distributed by size and found to have size-specific functions. Finally, expression levels of microRNAs in several C. elegans models of Parkinson’s disease were measured and two differentially regulated microRNA families were identified as potentially involved in Parkinson’s disease-associated pathogenic mechanisms. In conclusion, the effectiveness and functions of exogenous and endogenous small RNAs were studied in order to provide a more thorough understanding of their biology with the prospect of using this information in development of small RNA-based therapies for neurodegenerative diseases. Universal Decimal Classification: 575.113, 577.113, 577.218, 595.132 National Library of Medicine Classification: QU 475, QX 203, WL 359, QY 58 Medical Subject Headings: Gene Expression Regulation; Gene Silencing; RNA, Small Interfering; MicroRNAs: RNA Interference; Nematoda; Caenorhabditis elegans; Microarray Analysis; Neurons; Phosphorylation; Proteins; Embryonic Development; Sperm Motility; Neurodegenerative Diseases/therapy; Parkinson Disease; Disease Models, Animal To Ari Mom and Dad Susanna and Ari-Pekka And the cats Topi and Pehmo
Do cytochrome c oxidase 1 Gene Sequences Differentiate Species of Spirostreptid Millipedes (Diplopoda: Spirostreptida: Spirostreptidae)?

ABSTRACT The aim of this study was to use cytochrome c oxidase 1 (CO1) sequences to recover a phylogeny for seven morphologically described spirostreptid millipede taxa from southern Africa, and to evaluate the correspondence between morphological and molecular phylogenies. Genetic p-distance generally increased with taxonomic divergence: inter-specific mean 15.33 % (14.09 % –17.02 %), inter-generic mean 18.43 % (6.83 %–26.81 %) and inter-order mean 24.16 % (range 18.56 %–30.77 %). Congruent Bayesian, maximum parsimony and neighbour-joining analyses of 520 nucleotides of the CO1 gene resolved the orders Spirostreptida, Julida and Callipodida. Members of genera within the Spirostreptidae (Archispirostreptus, Bicoxidens, Cacuminostreptus, Doratogonus, Orthoporoides, Plagiotaphrus and Spirostreptus) formed a single clade within which a sample of Thyropygus (family Harpagophoridae) was paraphyletically nested. Phylogenetic analyses failed to recover support for the genera Doratogonus, Bicoxidens, Archispirostreptus and Spirostreptus, as representatives of these genera were not monophyletic. Samples morphologically identified as the same species (Bicoxidens flavicollis) were part of two different clades, one of which was well supported and otherwise contained members of Doratogonus. This high level of divergence (mean 12.64 %) between morphologically identified spirostreptid millipede sister species could indicate that changes in genital morphology occur rather slowly relative to CO1 sequence substitution, and may underestimate species diversity.
Habitat suitability assessment for the endangered Nilgiri Laughingthrush: A multiple logistic regression approach

Application of remote sensing and Geographic Information System (GIS) tools has assumed an increasingly important role in conservation biology and wildlife management by providing means for modelling potential distributions of species and their habitats, unlike the conventional ground surveys. We present here a predictive model of habitat suitability for the Nilgiri Laughingthrush, Garrulax cachinnans based on a synergistic use of field surveys and digitally processed satellite imagery combined with features mapped using GIS data layers. Collateral data were created in a GIS framework based on ground surveys comprising layers such as landuse, measures of proximity to likely features of disturbance and a digital terrain model. Multiple binomial logistic regression approach was used for modelling, and the model performance was assessed by the area under the receiver operating characteristics (ROC) curve. About 320 km 2 , 25.12% of the area of the Nilgiris considered for modelling was predicted to be suitable for the Nilgiri Laughingthrush. The area under the ROC curve was found to be 0.984 ± 0.003 (R 2 : 0.93 at P < 0.0001), implying a highly effective model. The assessed suitable habitat was highly fragmented and comprised of 1352 patches (natural as well as manmade) distributed all over the study area. The smallest suitable patch identified by the model was 400 m 2 and the largest patch 17.65 km 2 . Also, ca. 92% of all patches were smaller than 0.5 km 2 . We presume that some suitable habitat patches may be unoccupied due to strong fidelity of the species to shola (montane wet temperate forest) patches, low colonization rates, or large inter-fragment distances. Also, larger fragments might serve as source or 'exporters' of surplus individuals to maintain sink populations throughout the rest of the range. We discuss the implication of habitat fragmentation and narrow geographical range and anthropogenic pressure for the conservation of the Nilgiri Laughingthrush.
The Golden Bridge for Nature: The New Biology Applied to Bioplastics

There is a common concept in life: large and complex molecules result from the synthesis of units that are later joined together. Mankind learned this principle and employed it to develop language, culture, and technology. This same principle is applied in the petrochemical industry by fractionating the fossilized carbon chains into small molecules and then polymerizing them in order to develop synthetic polymers, which are much more flexible, resistant, and durable than natural polymers. Recent developments in molecular biology have opened the possibility of modifying organisms in order to create new biosynthetic routes for the production of monomers that would fit the biggest challenge in modern society: the production of high quality polymers from renewable feedstocks. This review focuses on the latest advances in molecular biology and the new knowledge and technologies that enable the possibility of converting cells into efficient and sustainable chemical reactors. The first examples of this technological advancement are already in the market.
Glucoamylase‐like domains in the α‐ and β‐subunits of phosphorylase kinase

Phosphorylase kinase is a four‐subunit enzyme involved in the regulation of glycogen breakdown. The traditional textbook view is that only the γ subunit has enzymatic activity, whereas the other three subunits have a regulatory role. Evidence from homology searches and sequence alignments, however, shows that the α‐ and β‐subunits possess amino‐terminal glucoamylase‐like domains and suggests that they might possess a previously overlooked amylase activity. If true, this would have important implications for the understanding, diagnosis, and management of glycogen storage diseases. There is thus a clear need to test this hypothesis through enzymatic assays and structural studies.
Methods to improve the viability and stability of probiotics

Publisher Summary Probiotic functional foods face high technological demands since probiotics, live microorganisms which when administered in adequate amounts confer a health benefit on the host, have to retain their viability during all the production steps and even in the Gastrointestinal [“GI”] tract of the consumer. The aim of industrial probiotic production is to produce in an affordable manner high-quality, safe end-products with long enough shelf-life. For the food industry an easy formulation of probiotic preparations into products is of concern. Thus, probiotic preparations are usually provided as highly concentrated Direct Vat Inoculation [“DVI”] products, which can be directly used at the probiotic food production site. For the successful production of high-quality probiotic products a good knowledge on the strain-specific characteristics is necessary. Viability losses of probiotic microbes unavoidably occur during their processing and formulation steps, but with a strong know-how of the production strain these losses can be minimized. A common feature for most probiotic strains is that they are specialized in living in the human or animal GI tract, which makes them well adapted to that special environment but poorly adapted to other environments. Microbes that survive and thrive in the GI tract can be difficult to propagate and down-stream process in both small and large scale. Typical problems in probiotic technology are difficulties in obtaining high cell concentrations during growth, and retaining viability during down-stream processing, formulation and in the end product.
A genetic linkage map of olive based on amplified fragment length polymorphism, intersimple sequence repeat and simple sequence repeat markers.

A detailed genomic linkage map of the olive (Olea europaea L. ssp.europaea (2x=2n= 46)) was constructed with a 147 F1 full-sib 'Olivi` · 'Arbequina' progeny in a two-way pseudo-test cross-mapping configuration. Based onalogarithmofoddsthresholdof6andamaximumrecombination fractionof0.4,maternalandpaternalmapswere constructed using 222 makers (178 amplified fragment length polymorphism (AFLP), 37 simple sequence repeat (SSR),sevenintersimplesequencerepeat(ISSR))and219markers(174AFLP,39SSR,6ISSR)markers,respectively. The female map regrouped 36 linkage groups (LGs) defining 2210.2 cM of total map length with an average marker spacing 11.2 cM and a maximum gap of 48.5 cM between adjacent markers. The male map contained 31 LGs and covered a distance of 1966.2 cM with an average and a maximum distance between two adjacent markers of 10.3 and 40.4 cM, respectively. Mean LG size was 61.3 and 63.4 cM in the maternal and paternal maps, respectively. The LGs consisted of two to 17 loci (up to 21 loci in the paternal map) and ranged in length from 2.7 to 182 cM (female map) or from4.1 to 218.1 cM(paternal map). Markers were distributed throughout the mapswithoutanyclustering. Thetotal length of the consensus map was 3823.2 cM containing 436 markers distributed into 42 LGs with a mean distance between two adjacent loci of 8.7 cM. Both parental maps and the consensus maps were compared with previously published olive maps. Although not saturated yet, the present maps offer a promising tool for quantitative trait loci mapping because phenotypic characterization of the cross is currently carried out. Olive is one of the most important Mediterranean fruit species cultivated for oil and canned fruit consumption. With over 2000 cultivars, the olive tree is highly diverse and adapted to Mediterranean agroecological conditions. It plays a major socioeconomical role in traditional agroecosystems, especially in southern Mediterranean areas with an expanding use in oil and cosmetic industries (Aburjai and Natsheh, 2003). Olive is a diploid species (2n = 46 (Green and Wickens, 1989)) with a nuclear DNA content ranging from 2.90 ± 0.020
Bioaccumulation of Some Heavy Metals and Histopathological Alterations in Liver of Oreochromis niloticus in Relation to Water Quality at Different Localities along the River Nile, Egypt

2 Abstract: Fish samples were collected from the River Nile and its two branches (Damietta and Rossetta). The sampling stations were El-Oqsur, El-Menia, El-Hawamdia, Shoubra El-Khema, El-Rahawy drain, Kom Hamada, Talkha, El-Serw and Faraskour. The accumulation of Iron, Manganese, Copper, Zinc, Cadmium and lead in liver of collected O. niloticus fish from the above stations were determined. In addition, the same liver samples were examined histopathologically. Results showed that trace metals accumulations in fish liver at area under investigation were detected in following descending order: Fe > Cu > Zn > Mn > Pb > Cd. Histological study indicated that the liver of O. niloticus living in the studied stations showed several pathological alterations including: degeneration, fatty degeneration, necrosis and edema. Also congestion, branching (anastimosis), hemorrhage, hemolysis, hemosidrin and parasitic forms were seen in blood vessels. It was noticed that the liver of fish collected from Shoubra El-Khema, El-Hawamdia, El-Rahawy drain and El-Menia showed much more damages than that collected from the other stations as these sites receives more drainage water loaded with industrial and sewage wastes than the other stations. It was concluded that the discharge of different types of wastes, especially heavy metals deteriorated the water quality in the River Nile and consequently affecting fauna and fish production and human health. It is recommended to treat the different wastes before discharging to the River Nile Stream.
α3Aβ1 integrin localizes to focal contacts in response to diverse extracellular matrix proteins

In vitro binding assays and inhibition of cell adhesion with monoclonal antibodies have implicated the integrin α3β1 as a receptor for a variety of extracellular ligands. However, reports of α3β1-ligand interactions are inconsistent, and transfection studies have suggested that α3β1 is not sufficient for cell attachment to ligands other than kalinin/laminin 5. We used immunofluorescence to study subcellular localization of the α3A cytoplasmic domain variant in different cultured cell types. Using standard fixation and permeabilization methods, antibodies specific for α3A stained most cell types in a diffuse pattern, consistent with previous reports. Surprisingly, however, chemical cross-linking of integrins to the extracellular matrix and extraction of the cytoskeleton prior to immunofluorescence revealed α3A in focal contacts of most cells tested, suggesting that the cytoplasmic domain was concealed in intact focal contacts by cytoskeletal or other cytoplasmic proteins. The α3A subunit localized to focal contacts in several cell types cultured on fibronectin, kalinin/laminin 5, EHS-laminin/laminin 1, type IV collagen, or vitronectin. In contrast, α5 and αV integrins were detected in focal contacts only in cells grown on their known ligands (fibronectin, and fibronectin or vitronectin, respectively). Therefore, our results show that α3Aβ1 responds to a broad spectrum of extracellular ligands. Time course comparisons of the recruitment of α subunits from different fibronectin receptors suggested that localization of α3Aβ1 to fibronectin-induced focal contacts was independent of the recruitment of α5 and α4 integrins. However, other studies have shown that α3Aβ1 does not mediate initial cell adhesion to many of the ligands that induced its focal contact localization, including fibronectin. Therefore, we suggest that α3Aβ1 may be a secondary receptor with post-cell-adhesion functions for a broad spectrum of extracellular matrices. SUMMARY
DNA barcoding Cinnamomum osmophloeum Kaneh. Based on the partial non-coding ITS2 region of ribosomal genes

This paper investigated the DNA barcoding of indigenous cinnamon. The essential oil composition of leaves and the partial non-coding internal transcribed spacer (ITS2) region of ribosomal genes from indigenous cinnamon plants (Cinnamomum osmophloeum Kaneh.) were investigated. Leaf essential oils from seven geographical strains of C. osmophloeum Kaneh. were obtained by hydrodistillation and characterized by gas chromatography-mass spectrometry. Six chemotypes, including cinnamaldehyde, cinnamaldehyde/cinnamyl acetate, cinnamyl acetate, linalool, camphor and mixed, were identified. Seven representative geographical strains were further used to study their genetic diversity based on the partial ITS2 region using PCR amplification and DNA sequencing to evaluate the region's use in the application of DNA barcoding C. osmophloeum Kaneh. A phylogenetic tree was constructed using UPGMA clustering method. Our results indicate that the partial ITS2 nucleotide sequences for all seven geographical strains are identical and not correlated with essential oil composition. The partial ITS2 sequences is sufficient for barcoding C. osmophloeum Kaneh. , while that additional genes will need to be analyzed to identify samples of various chemotypes. We believe that this partial ITS2 locus serves as a good starting point for large-scale testing of DNA barcoding of other plant species across Taiwan.
New host records for ticks (Ixodidae) from the northern quoll (Dasyurus hallucatus) in north Queensland

Abstract. Ticks (Ixodidae) were collected from northern quolls (Dasyurus hallucatus) from three sites on the Atherton Tableland, north Queensland. Four species of ticks (Haemaphysalis humerosa, Ixodes fecialis, I. holocyclus and I. tasmani) were collected from quolls. Prevalence of infestation of ticks varied from 44 to 92% across the three sites. The collection of the three species of Ixodes represents new host records for D. hallucatus, thus adding valuable new details to the ecology of the parasite fauna of an endangered marsupial.
New species and new records of chewing lice (Phthiraptera: Amblycera and Ischnocera) from bulbuls (Passeriformes: Pycnonotidae) in Vietnam

Seven species of chewing lice (Insecta: Phthiraptera) were found on five species of bulbuls (Passeriformes: Pycnonotidae) in northern Vietnam. Three new species of the genera Brueelia and Philopteroides are described; they and their type hosts are: Brueelia flavala ex Hemixos flavala Blyth, 1845 B. cucphuongensis ex Pycnonotus finlaysoni Strickland, 1844 and Philopteroides flavala ex Hemixos flavala Blyth, 1845. First records of chewing lice from Hemixos castanonotus Swinhoe, 1870 and Iole propinqua (Oustalet, 1903), and a new host record for Myrsidea ochracei and Sturnidoecus sp. are also included.