Conjugation of phosphonoacetic acid to nucleobase promotes a mechanism-based inhibition

Small molecule inhibitors have a powerful blocking action on viral polymerases. The bioavailability of the inhibitor, nevertheless, often raise a significant selectivity constraint and may substantially limit the efficacy of therapy. Phosphonoacetic acid has long been known to possess a restricted potential to block DNA biosynthesis. In order to achieve a better affinity, this compound has been linked with natural nucleotide at different positions. The structural context of the resulted conjugates has been found to be crucial for the acquisition by DNA polymerases. We show that nucleobase-conjugated phosphonoacetic acid is being accepted, but this alters the processivity of DNA polymerases. The data presented here not only provide a mechanistic rationale for a switch in the mode of DNA synthesis, but also highlight the nucleobase-targeted nucleotide functionalization as a route for enhancing the specificity of small molecule inhibitors.     

Description of Crenosoma vismani n. sp., parasitic in the lungs of Lynx lynx (L.) (Carnivora: Felidae), with identification key to the species of the genus Crenosoma Molin, 1861 (Nematoda: Crenosomatidae)

A new species of Crenosoma Molin, 1861 is described from the lungs of the Eurasian lynx, Lynx lynx (L.) (Carnivora: Felidae). Crenosoma vismani n. sp. differs from other species of the genus in the morphology of the male copulatory organs (two ventral rays originating from a common stem; three lateral rays with common stem; gubernaculum 79–92 μm long, well developed, spoon-shaped; spicules 232–253 μm long, slightly curved, with robust dorsal appendage) and a vulva with rounded, prominent vulvar cuticular appendage is located in middle region of body in females. An analysis of the morphology and life-cycle data for Crenosoma petrowi Morozov, 1939 from Ursus americanus Pallas indicate that this nematode should be described as a new species. The validity of Crenosoma schulzi Gagarin, 1958 is resurrected. A new identification key for the species of Crenosoma is provided. Published records of the genus Crenosoma from definitive hosts and patterns of host specificity are presented. Morphological data revealed that the genus Crenosoma should contain 15 species (14 with valid names) with different host specificity, ranging from oioxenous to euryxenous. However, a review of the current genetic data indicates that the actual number of Crenosoma spp. is greater, and the host range is still unknown, even in Europe.

     

Autofluorescence imaging for recurrence detection in skin cancer postoperative scars

This clinical study is a first attempt to use autofluorescence for recurrence diagnosis of skin cancer in postoperative scars. The proposed diagnostic parameter is based on a reduction in scar autofluorescence, evaluated in the green spectral channel. The validity of the method has been tested on 110 postoperative scars from 56 patients suspected of non‐melanoma skin cancer, with eight patients (13 scars) available for the repeated examination. The recurrence diagnosis within a scar has been made after two subsequent autofluorescence check‐ups, representing the temporal difference between the scar autofluorescence amplitudes as a vector. The recognition of recurrence has been discussed to represent the significant deviations from the value of vector angle θ. This new autofluorescence‐based method can be easily integrated into the postoperative monitoring of surgical scars and can help diagnose the recurrence of skin cancer from the early stage of scar development.     

Multistep Photoluminescence Decay Reveals Dissociation of Geminate Charge Pairs in Organolead Trihalide Perovskites

Charge carrier dynamics in organolead iodide perovskites is analyzed by employing time‐resolved photoluminescence spectroscopy with several ps time resolution. The measurements performed by varying photoexcitation intensity over five orders of magnitude enable separation of photoluminescence components related to geminate and nongeminate charge carrier recombination and to address the dynamics of an isolated geminate electron–hole pair. Geminate recombination dominates at low excitation fluence and determines the initial photoluminescence decay. This decay component is remarkably independent of the material structure and experimental conditions. It is demonstrated that dependences of the geminate and nongeminate radiative recombination components on excitation intensity, repetition rate, and temperature, are hardly compatible with carrier trapping and exciton dissociation models. On the basis of semiclassical and quantum mechanical numerical calculation results, it is argued that the fast photoluminescence decay originates from gradual spatial separation of photogenerated weakly bound geminate charge pairs.     

Release of Free DNA by Membrane-Impaired Bacterial Aerosols Due to Aerosolization and Air Sampling

We report here that stress experienced by bacteria due to aerosolization and air sampling can result in severe membrane impairment, leading to the release of DNA as free molecules. Escherichia coli and Bacillus atrophaeus bacteria were aerosolized and then either collected directly into liquid or collected using other collection media and then transferred into liquid. The amount of DNA released was quantified as the cell membrane damage index (I_D), i.e., the number of 16S rRNA gene copies in the supernatant liquid relative to the total number in the bioaerosol sample. During aerosolization by a Collison nebulizer, the I_D of E. coli and B. atrophaeus in the nebulizer suspension gradually increased during 60 min of continuous aerosolization. We found that the I_D of bacteria during aerosolization was statistically significantly affected by the material of the Collison jar (glass > polycarbonate; P < 0.001) and by the bacterial species (E. coli > B. atrophaeus; P < 0.001). When E. coli was collected for 5 min by filtration, impaction, and impingement, its I_D values were within the following ranges: 0.051 to 0.085, 0.16 to 0.37, and 0.068 to 0.23, respectively; when it was collected by electrostatic precipitation, the I_D values (0.011 to 0.034) were significantly lower (P < 0.05) than those with other sampling methods. Air samples collected inside an equine facility for 2 h by filtration and impingement exhibited I_D values in the range of 0.30 to 0.54. The data indicate that the amount of cell damage during bioaerosol sampling and the resulting release of DNA can be substantial and that this should be taken into account when analyzing bioaerosol samples.     

Astrocyte–Endotheliocyte Axis in the Regulation of the Blood–Brain Barrier

Neurochemical Research - The evolution of blood–brain barrier paralleled centralisation of the nervous system: emergence of neuronal masses required control over composition of the...     

Factors Controlling Phytoplankton Blooms in a Temperate Estuary: Nutrient Limitation and Physical Forcing

A combination of enclosure nutrient enrichment experiments and historical data analysis was used to identify the factors controlling seasonal dynamics and competition of the phytoplankton community in the Curonian lagoon (Southeast Baltic Sea). Experiments using different nutrient (N, P and Si) manipulations were performed in 10-l enclosures for 48 h. Changes in chlorophyll a concentrations, inorganic nutrient concentrations, and plankton cell density were monitored. Results revealed that phytoplankton development in the lagoon is strongly affected by ambient physical factors (wind, temperature). Nutrient limitation, however, also plays an important role in seasonal succession mechanisms showing quite distinct seasonal development patterns. Based on the data, available phytoplankton seasonal succession in the Curonian lagoon could be described as composed by three phases corresponding to different domination and regulatory mechanisms.     

Interrelationships between distinct circadian manifestations of possible bruxism,perceived stress,chronotype and social jetlag in a population of undergraduate students

ABSTRACT

This study investigates the recently hypothesized association between distinct circadian manifestations of possible bruxism in subjects with different chronotype profiles, social jetlag and levels of perceived stress. A cross-sectional study was performed by surveying dental students’ of Lithuanian University of Health Sciences. A survey instrument was designed and pilot tested for reliability and validity prior to full-scale administration. The instrument consisted of four sections: socio-demographic questions, bruxism-related items, the Perceived Stress Scale and the Munich ChronoType Questionnaire. The study included 228 students (82.5% females; mean age 22.67 ± 2.27). Awake grinding was significantly associated with later chronotype values (p = 0,039). Despite the lack of significance, binary regression models demonstrated that students with later chronotypes report higher rates of possible bruxism, especially as far as awake grinding (p = .170; OR = 1.89) and sleep grinding (p = .140; OR = 1.60) are concerned. There were no significant associations between perceived stress, social jetlag and bruxism. The scores of perceived stress did not correlate with chronotype values, although a high positive correlation was found between chronotype and social jetlag (r = 0.516, p = .000). It can be concluded that later chronotypes increase the odds for self-reported bruxism, and are significantly associated with higher rates of awake grinding and social jetlag. No interrelationships were found between perceived stress, possible bruxism and social jetlag.     

Aroma Components of Baelfruit (Aegle marmelos CORREA)

The attractive and characteristically sweet aroma components of baelfruit—a tropical fruit— were investigated. The aroma concentrates possessing the sweet floral and somewhat terpene-like aroma were obtained from both the pulp and peel of fresh baelfruits by means of lyophilization and ether extraction, being analyzed mainly by GC-MS, A total of 39 components were identified. Among these components, terpene alcohols and β-βonone were considered to contribute to the aroma of baelfruit. At optimum ripeness, the fruit with excellent flavor contained a large quantity of an isomeric compound of 3,7-dimethyl-1,5,7-octatrien-3-ol. This compound couldn’t be found in unripe fruit, and seems to be ?mportant in making the baelfruit flavor attractive.