Miracle-dz/UniFAR-FTUs huggingface dataset:
Using Metabolomics for Elucidating the Mechanisms Related to Tuberculosis Treatment Failure

Tuberculosis (TB), caused by Mycobacterium tuberculosis is a highly infectious disease, responsible for 1.4 million deaths annually. Unfortunately, the latest reports of treatment outcomes for patients using the current anti-TB drugs are disappointing, considering the high treatment failure rates. This has been ascribed to a number of factors, including, amongst others: (1) variable individual metabolism (including xenobiotic metabolism, drug malabsorption and drugdrug interactions), (2) drug resistance by the infectious organism and (3) non-adherence to the treatment program, especially due to the associated drug side-effects. Despite this however, only two new drugs have been approved by the FDA since 1962. Thus, it is clear that new strategies are needed for the better elucidation of in vivo anti-TB drug mechanisms and their associated side-effects, and the mechanisms by which the infectious organism develops drug resistance. To this end, the relatively new research approach termed ‘metabolomics’, shows promising results through its capacity for identifying new drug markers, or metabolic pathways related to these contributing factors. Metabolomics refers to the unbiased identification and quantification of all metabolites (products of bio-molecular processes) present in a biological system, using highly selective and sensitive analytical methods. The application of metabolomics, for biomarker discovery, is based on the principle that an external stimulus, such as TB disease or infection, an anti-TB drug, or a mutation resulting in drug resistance, may disrupt normal metabolism, altering the overall physiological status of an organism or host, and these metabolic changes are specific to the perturbation investigated and not due to overall inflammation or disease process. Analyses of these altered metabolic pathways, may subsequently shed new light on the mechanisms associated with the causes of treatment failure, and ultimately lead to new treatment strategies which may most likely be aimed at targeting specific metabolic pathways in M. tuberculosis, and/or the genes/proteins associated with these.
Things I'd Never Thought About

There's so much I don't know! I think all general bio teachers feel this way. A field that encompasses the entire living world is very daunting. We are comfortable in certain areas, while in others our ignorance may be coated by only a thin veneer of information. This ignorance can be divided into two categories: things we know that we don't know, and things we have never even considered. In the first category, I would, in my own case, include the fine points of taxonomy, invertebrate physiology, and any botany beyond the most elementary. In the second category, it is impossible to know just what to include. That's the point, the category includes all those things that it never even dawned on me to contemplate. For example, how can microscopic bacteria slow down a supertanker? Can a mastectomy reduce fertility? Does the intestinal lining develop and atrophy in response to changes in use the way muscle tissue does? I've recently discovered answers to these and other questions, questions I'd never thought to ask. In some cases, it seems that no one else had thought to ask them either until quite recently. In other cases, curiosity had led investigators to these areas years ago, and it was just my ignorance that prevented me from discovering them until now. In this column, I'll discuss a few of these points in the hope that at least some of them will come as news to you too.
The effects of a hurricane on seedling dynamics and abiotic interactions in a tropical lower montane wet forest

Abstract: We assessed seedling dynamics and understorey light before and after a hurricane in five randomly selected 5 × 5-m subplots, within 30 permanent sample plots covering a total area of 3750 m2 in a lower montane wet tropical forest, Jamaica over a period of 3 y. Understorey light increased (≈ 60%) following the passage of Hurricane Dean in 2007 but decreased in 2009. Overall, seedling density was positively related to light and survivorship was positively related to both light and density. Mortality was significantly lower and most species recorded their highest growth when the canopy was open (2007–2008). However, lower diversity during this period coincided with higher (average) mortality of uncommon species. The hurricane altered the relative importance of interactions between light, seedling density and dynamics. Consequently, interactions were significant before or 2 y after but not 1 y after the hurricane and their significance varied among the years and species. Periodic changes in the importance of these interactions and the effects of the hurricane were used to separate 12 common species along a continuum of responses, which ranged from positive (lower mortality), neutral to negative (lower growth). Our results indicate that hurricanes have positive and negative effects on seedling dynamics; therefore an increase in the intensity and frequency of hurricanes will likely alter seedling composition, and hence forest structure.
Evaluation of safety and potency of rabies vaccines.

Quality control of rabies vaccines should be conducted at two levels, by the manufacturer and by a national control authority, e.g. the national rabies laboratory or national Veterinary Service laboratory. The methods for quality control of rabies vaccines were revised by a W H O Expert Committee in 1983. They are summarised in the Seventh Report of the W H O Expert Committee on Rabies (Technical Report Series 709, 1984).
Aculeus Wear and Oviposition in Four Species of Tephritidae (Diptera)

Structural degradation of the aculeus in tephritid flies was studied with scanning electron microscopy. We examined the aculei for tip wear or abrasion in Rhagoletis pomonella (Walsh) (60 specimens), R. mendax Curran (19 specimens), Ceratitis capitata (Wiedemann) (38 specimens), and Bactrocera oleae (Gmelin) (8 specimens). More than 70% of the 71 field-collected flies showed definite wear of the aculeus tip, whereas <10% of the 54 specimens preserved following eclosion had some aculeus tip wear. Fly age, oviposition in preexisting holes, and multiple egg laying in single oviposition punctures are discussed in relation to aculeus tip wear. This study suggests that structural degradation of the aculeus caused by oviposition and other activities may be responsible for alterations in tephritid oviposition behavior.
Korenine slovenskega samospeva

Clanek se posveca Linhartovim uglasbitvam dveh pesmi iz njegovega almanaha (1781). Cetudi gre za skladbi, ki sta 60 let starejsi od obicajno datiranega zacetka slovenske samospevne literature, njuna skromna glasbena faktura in intimisticni znacaj opozarjata na iste estetske principe, ki veljajo za vzorcne primere te zvrsti, s katerimi ju druži tudi izvedbena priložnost znotraj krožka mescanskega salona.
Microstructure and optical properties of thermally evaporated very thin silver films

The present paper shows results for the optical properties of nanocrystalline silver thin films in attempt to understand the effects of the particle size. Ag-films with thickness from 10 nm to 20 nm were deposited on optical glass by thermal evaporation. Depending on the deposition rate, due to different sizes of the grains building the layers, it was observed variation in the color of the coatings from red to blue. The grain size was determined by X-ray diffraction from the formula of Debye-Scherrer. A strong absorption band due to surface plasmons was observed in the transmittance spectra of the films. The absorbance maximum is positioned in the spectral range 400–550 nm in dependence of the film’s grains size. The evolution of the thin silver films during vacuum annealing was investigated. It was established that the heating of 25 nm films at 250oC leads to aggregation of the grains.
Germ Cell Determinant Transmission, Segregation, and Function in the Zebrafish Embryo

Animals specify primordial germ cells (PGCs) in two alternate modes: preformation and epigenesis. Epigenesis relies on signal transduction from the surrounding tissues to in‐ struct a group of cells to acquire PGC identity. Preformation, thought to be the more de‐ rived PGC specification mode, is instead based on the maternal inheritance of germ celldetermining factors. We use the zebrafish as a model system, in which PGCs are specified through maternal inheritance of germ plasm, to study this process in vertebrates. In ze‐ brafish, maternally inherited germ plasm ribonucleoparticles (RNPs) have co-opted the cytoskeletal machinery to reach progressive levels of multimerization, resulting in the formation of four large masses of aggregated germ plasm RNPs. At later stages, germ plasm masses continue to use components of the cell division machinery, such as the spindles, centrosomes, and/or subcellular organelles to segregate asymmetrically during cell division and subsequently induce germ cell fate. This chapter discusses the current knowledge of germ cell specification focusing on the zebrafish as a model system. We al‐ so provide a comparative analysis of the mechanism for germ plasm RNP segregation in zebrafish versus other known vertebrate systems of germ cell preformation, such as in amphibian and avian models.
β1-Adrenergic Receptors Mediate β3-Adrenergic-Independent Effects of CGP 12177 in Brown Adipose Tissue

CGP 12177 is a β-adrenergic receptor (AR) ligand that has been used to characterize the β3-AR and the putative β4-AR. The ability of CGP 12177 to activate β1-AR when overexpressed in vitro and the presence of β1-AR in tissues expressing putative β4-AR prompted us to investigate the actions of CGP 12177 at recombinant and natively-expressed β-AR. CGP 12177 potently activated recombinant rat and human β1-AR expressed in Chinese hamster ovary cells. This activation, like that of putative β4-AR, was resistant to blockade by selective and nonselective β-AR antagonists. Brown fat has been proposed to contain β4-AR, as evidenced by the presence of CGP 12177-mediated thermogenesis in mice lacking β3-AR. Therefore, the identity of the receptors mediating CGP 12177 responses in brown fat was examined using wild-type mice and mice lacking β1-AR or β3-AR. In wild-type mice, CGP 12177 activated adenylyl cyclase via high- and low-affinity sites. The high-affinity site, but not the low-affinity site, was blocked by CGP 20712 with potency indicating an interaction with β1-AR. Moreover, the high-affinity site was absent in mice lacking β1-AR. In contrast, the low-affinity, CGP 20712-resistant activation by CGP 12177 was absent in mice lacking β3-AR. Rather, activation occurred exclusively through the high-affinity, CGP 20712-sensitive site. These data indicate that the actions of CGP 12177 in brown fat that have been attributed to novel β-AR (i.e., β4-AR) are mediated via an atypical interaction with β1-AR.
Effect of Green Manure, Wheat Strawand Organic Manureson DTPA Extrac table Fe, Mn, Zn and Cu in a Calcareous Sandy Loam Soil at Field Capacity and under Waterlogged Conditions

Kinetics of DTPA extractable Zn, Cu, Fe and Mn were studied in a calcareous sandy loam soil incubated with green manure (Sesbaniaa culeata), wheat straw and cattle and poultry manures. At field capacity, while Zn and Cu started decreasing after one week of incubation, DTPA-Fe and -Mn exhibited peak concentrations at 4 weeks. Organic amendments did not affect the availability of micronutrients at field capacity. However, under continuous flooding, organic amendments in general and sesbania green manure and poultry manure in particular increased several fold the DTPA extractable Fe and Mn up to 4 and 8 weeks, respectively. Highest values of DTPA-Zn under flooded conditions were also observed when the soil was treated with poultry manure and sesbania green manure. Lowest values were recorded in the soil amended with wheat straw. Irrespective of organic amendments, DTPA-Zn however, continued to decrease during 12 weeks of anaerobic incubation. Concentration of Cu in DTPA extracts of amended soil was more than that of unamended soil throughout 12 weeks of submergence.
Phytochemistry and Pharmacology of an Important Indian Medicinal Plant Crataeva nurvala Buch Ham

Crataeva nurvala Buch. Ham. (Capparidaceae) is a high-value medicinal tree that grows almost all over India, especially in the semiarid regions. Medicinal usage has been reported in traditional systems of medicine, such as Ayurveda and Unani. This drug is used in traditional system of medicine against a wide variety of urinary disorders. Crataeva nurvala is commonly known as Varuna. Many phytoconstituents have been isolated from the fruits, root bark and stem bark of Varuna. Lupeol is the major chemical constituent isolated from Varuna. The minor chemical constituents are cadabicine, cadabicinediacetate, catechin, (−)epicatechin5-glucoside, (−)epiafzelechin, glucocapparin, lupeol acetate, spinasterol acetate and taraxasterol. Lupeol, a pentacyclic triterpene isolated from the root bark, has been shown to significantly minimize the deposition of stone-forming constituents in kidneys. Investigations have also indicated the plant has anti-arthritic, hepatoprotective, and cardio-protective actions. This review briefly examines the Phytochemistry, biological activities, pharmacological actions, clinical studies, and medicinal applications of Crataeva nurvala to provide direction for further research.
Biochemical population genetics of Atlantic herring, Clupea harengus

for the gene products of 40 protein-coding loci using starch gel electrophoresis. A nested contingency-table analysis, a cluster analysis of genetic distances between populations and a gene-diversity analysis of allele-frequency data each showed that there was little genetic differentiation among North American populations and among European populations. These analyses also showed that the magnitude of transoceanic differentiation was not greater than that among regions on both sides of the Atlantic Ocean. The lack of transoceanic differentiation could be explained by a radiation model where a single population, which might have been restricted to one side of the Atlantic Ocean by coastal glaciation during the Pleistocene, radiated into several populations that do not now exchange genes.
A novel pattern of smoltification in the most anadromous salmonid: pink salmon (Oncorhynchus gorbuscha)

Pink salmon (Oncorhynchus gorbuscha) enter seawater earlier and smaller (0.2 g) than any other salmonid following a two-stage salinity tolerance process initiated around yolk-sac absorption and completed with seawater entry. For the first time, this two-stage ontogeny of salinity tolerance was characterized by either holding posthatch pink salmon in fresh water or transferring them to seawater every 2 weeks. A window of salinity tolerance around yolk-sac absorption was evidenced by a period of zero morbidity in seawater compared with 100% morbidity for newly hatched alevins and 25% morbidity for fry ( 0.2–0.3 g). Increased hypo-osmoregulatory ability at the time of yolk-sac absorption was indicated in fish held in fresh water under constant photoperiod (12 h light : 12 h dark) and temperature (5 °C) by a switch from catabolic to anabolic growth, increased gill Na+K+-ATPase activity and -1b/ -1a isoform expression, and a plateau in whole-body water content, implying that pink salmon go through a form of smoltification. A large increase in whole-body [Na+] observed in fresh water at yolk-sac absorption may represent a unique strategy for maintaining water balance once fish enter seawater. Resume : Le saumon rose (Oncorhynchus gorbuscha) fait son entree en eau demer plus tot et a plus petite taille (0,2 g) que tout autre salmonide, apres un processus d'adaptation a la salinite en deux etapes debutant aux alentours de l'absorption du sac vitellin et se terminant avec l'entree en eau de mer. Pour la premiere fois, cette ontogenie en deux etapes de la tolerance a la salinite a ete caracterisee soit enmaintenant des saumons roses post-eclosion en eau douce ou en les transferant en eau demer toutes les deux semaines. La presence d'une fenetre de tolerance a la salinite vers le moment de l'absorption du sac vitellin est indiquee par une periode de morbidite nulle en eau de mer, comparativement a une morbidite de 100 % chez les alevins nouvellement eclos et de 25 % pour le fretin ( 0,2–0,3 g). Une capacite accrue d'hypoosmoregulation aumoment de l'absorption du vitellin etait indiquee chez les poissons maintenus en eau douce dans des conditions de photoperiode (12 h de lumiere : 12 h d'obscurite) et de temperature (5 °C) constantes par le passage d'une croissance catabolique a une croissance anabolique, des augmentations de la Na+K+-ATPase branchiale et du rapport d'expression d'isoformes -1b/ -1a, et un plafonnement de la teneur corporelle globale en eau, ce qui signifie que le saumon rose subit une forme de smoltification. Une importante augmentation de la [Na+] corporelle globale observee en eau douce au moment de l'absorption du sac vitellin pourrait representer une strategie particuliere de maintien de l'equilibre hydrique une fois que les poissons entrent en eau de mer. [Traduit par la Redaction]
Extraction Optimization, Preliminary Characterization and Antioxidant Activity of Glycoproteins from the Muscle of Sepia pharaonis

The extraction, purification, preliminary characterization and antioxidant activity of glycoproteins from Sepia pharaonis muscle (SPMG) were investigated. The optimal extraction conditions were obtained using a Box-Behnken design. The crude SPMG was purified by DEAE-Cellulose 52 ion-exchange and Sephadex G-100 gel chromatography and two fractions (SPMG-I and SPMG-II) were obtained. SPMG-I and SPMG-II were rich in Glu, Asp, Leu, Arg and Lys with the molecular weight of 42.5 and 36.3 kDa, respectively. The glucose was the predominant monosaccharide composition of SPMG-I and SPMG-II. The existence of O-glycosidic linkage in SPMG-I and SPMG-II was demonstrated by a β-elimination reaction. SPMG-I and SPMG-II were characterized by FT-IR. SPMG, SPMG-I and SPMG-II showed excellent antioxidant activities and SPMG-I exhibited the highest antioxidant ability. These may provide theoretical basis for further system research and rational development and utilization of SPMG resource.
Territorial exclusion of Acrocephalus schoenobaenus by A. scirpaceus in reedbeds

A population of Acrocephalus schoenobaenus (L.) established in reedbeds disappeared when an about equal number of A. scirpaceus (Hermann) arrived later in the season. A control population of schoenobaenus in a nearby marsh area without any arrival of scirpaceus did not disappear. The effect is interpreted as a case of territorial exclusion scirpaceus being strongly dominant over schoenobaenus in its optimal habitat, reed, where schoenobaenus does not usually breed but commonly tries to establish its song territory. It is suggested that the strong active competition is a transient phenomenon resulting from recent redistributions and meetings of the two species, particularly the expansion of scirpaceus. The ousted schoenobaenus individuals presumably have very low fitness, and this species may therefore, in due time, narrow its niche, excluding at least dense reeds, and specialize for a more efficient exploitation of its remaining marshland habitats.
Cellular Sterol Accumulation Stimulated by Cholesterol 5β,6β-Epoxide in J774 Macrophages

Abstract A significant accumulation of cellular free cholesterol and steryl esters is observed in J774 macrophages when cells are exposed to low-density lipoproteins (LDL) containing cholesterol 5β,6β-epoxide. This cellular sterol accumulation is mainly due to the formation of esterified cholesterol and desmosterol. Cellular steryl esters increased to 39.4 and 22.4 μg/mg cell protein with 0.8 μM of cholesterol 5β,6β-epoxide and 3,5-cholestadien-7-one, respectively, whereas hardly detectable levels were observed with the absence of oxysterols. The total cellular sterols increased 45% above the value of control with cholesterol 5β,6β-epoxide. The uptake of [3H] cholesteryl oleate-LDL was also enhanced by cholesterol 5β,6β-epoxide. The rapid displacement of desmosterol with cholesterol was observed when cells were treated with cholesterol 5β,6β-epoxide or 3,5-cholestadien-7-one in the presence of LDL. Cholesterol 5β,6β-epoxide became associated with LDL in the culture conditions, and its uptake into J774 cells and the cytotoxicity were reduced significantly by the association with LDL. The comparison of selected oxysterols for their ability to stimulate cellular sterol accumulation indicated that cholesterol 5β,6β-epoxide is the most potent. Cholesterol esterification was enhanced significantly by cholesterol 5β,6β-epoxide whereas cholesterol 5α,6α-epoxide and 3,5-cholestadien-7-one produced a modest response. In contrast, although cholestantriol, the metabolic hydrolysis product of cholesterol epoxides, also associated with LDL, it showed no stimulating effect on both cellular sterol content and sterol esterification. These results indicate that some oxysterols, such as cholesterol 5β,6β-epoxide and possibly 3,5-cholestadien-7-one, stimulate cellular sterol accumulation in J774 macrophages and may play an important role in atherogenesis.
Structural and mechanistic characterization of two RNA-cleaving deoxyribozymes

The following studies have been focused on studying two catalytic DNA molecules, the 8-17 and bipartite deoxyribozymes; both of which cleave single-strand RNA molecules. A new technique was developed to study the 8-17 by correlating photo-induced oxidative damage to its structure and structure folding transitions. A detailed mechanistic study was performed on the bipartite deoxyribozyme. Detailed structural information of the bipartite deoxyribozyme was obtained by photo-induced crosslinking and detailed mutation analyses. The charge flow patterns within an intricately folded DNA complex, the 8-17 bound to a DNA pseudosubstrate, incorporating three helical elements and two catalytically relevant loops were extensively studied. The stacking preferences of the three constituent helices were studied and provided evidence for significant transitions within the complex's global geometry. The patterns further suggested varying levels of solvent exposure of the complex's constituent parts, and revealed that a catalytically relevant cytosine within the folded complex exists in an unusual structural/electronic environment. The bipartite deoxyribozyme was found to have a mechanism of significant complexity. A dissection of metal usage indicated the involvement of two catalytically relevant magnesium ions for optimal activity. The deoxyribozyme was able to utilize manganese(lI) as well as magnesium; however titration with hexaamminecobalt(III) chloride inhibited the activity of the bipartite; this suggests that it is a metalloenzyme that utilizes metal hydroXide as a general base. Overall, the bipartite deoxyribozyme appeared to be kinetically distinct not only from the self-cleaving ribozymes but also from other in vitro selected, RNA-cleaving deoxyribozymes. The catalytic core of the bipartite deoxyribozyme was studied by mutagenesis and photo-induced crosslinking. Mutation analyses of the catalytic core revealed that a stem structure is important for the catalytic activity of the deoxyribozyme and that four bases within both loop regions are possible candidates for the direct co-ordination with the catalytically relevant divalent metal ions. Thio-modified nucleotides were substituted throughout the bipartite bound to a DNA pseudosubstrate. The mapping of the crosslinked species and the mutagenesis data suggested the catalytic core of the bipartite folded in a way that positions a stem region of a hairpin close to active site of the enzyme.