Self-assembling linear and star shaped poly (ε-caprolactone)/poly[(meth)acrylic acid] block copolymers as carriers of indomethacin and quercetin

A amphiphilic linear AB, BAB, and star shaped (AB)(3) block copolymers of poly(E-caprolactone) (PCL)/poly(meth)acrylic acid (P(M)AA) are used for the preparation of nanoparticles and drug entrapment, where indomethacin and quercetin are employed as model drugs. Drug loading experiments with the nanoparticles based on PAA block copolymers demonstrate a higher efficiency for the star structure, whereas the PMAA star copolymer presents the lowest entrapment ability. The release properties are studied at room temperature and 37 degrees C in phosphate buffer solutions with pH equal to 5 and 7.4. The kinetic profiles show a strong relation to the copolymer's topology, indicating the lowest release rates from the star based superstructures, while the PMAA particles are less stable than those containing PAA segment(s)

Activity pattern and fat accumulation strategy of the Natterer’s bat (Vespertilionidae, Chiroptera) swarming population indicate the exact time of male mating effort

Studies concerning bat autumn swarming behavior suggest that the main purpose of this phenomenon is mating. However, the process of fat accumulation is crucial for surviving winter, and it seems to be in clear conflict with a need to strive for the opportunity to mate prior to hibernation. Investment in one activity limits the other one creating a trade-off between them. The aim of our study was to describe the activity pattern of each sex-age group (adult males, adult females, subadults) of the Natterer’s bat during swarming period and to investigate the fat accumulation process of adult males in the context of their reproductive strategy. Bats were captured by mist nets at the swarming site fortnightly from the early August until the late November. The age, sex, reproductive status, and body condition index (mass to forearm ratio, BCI) were recorded. The activity peak of both sexes, adults, and subadults was observed in the late September. That time in season, BCI of adult males was the lowest, and there was no correlation between the hour of an adult male capture and its BCI value within one night (rs = 0.23; p = 0.157). Such correlation was observed later in the season (early October: rs = 0.44; p = 0.020; late October: rs = 0.48; p = 0.002). A negative correlation between adult males’ BCI and proportion of adult females was found (r = 0.44; p = 0.000). We conclude that the activity peak of females is likely to be responsible for the effort of the mating behavior of the males, which is reflected by their low condition index. We suggest that the gleaning foraging strategy of Natterer’s bat allows the males to postpone their fat accumulation until just before hibernation

What has happened to the females? : population trends in the Aesculapian snake at its northern range limit

Populations at the edge of their main range of distribution are often exposed to suboptimal environments. They therefore exhibit a greater susceptibility towards habitat changes and often clearly differ in their structure and dynamics from populations in the main range. Here we define population parameters of the Aesculapian snake Zamenis longissimus, a species endangered in Europe, at its northern range limit based on data obtained in the valley of the River San (Bieszczady Mts., SE Poland) in 2009-2013. We focus on the spatial and temporal sex ratio patterns by comparing data obtained in 2009-2013 with published records from 1990 to 1998 and five other northern populations (1 from the main range, 1 at the northern edge of its contiguous range, and 3 entirely isolated ones). Using the capture-mark-recapture (CMR) method, we estimated the population size to be about 230 snakes. Our data show that among adults the percentage of females (17.74%) in the San valley population was significantly lower than in those other five populations and the same population studied two decades earlier. Because of the male-biased sex ratio, we estimated the effective population size to be about 74 snakes. This disproportion between the sexes in adults may be interpreted as an early stage of the population extinction process at the northern range limit of this species’ distribution. It is probably due to the limited availability of egg-laying sites, compelling females to undertake longer movements, which may heighten the risk of mortality. Keywords: Zamenis longissimus, Population size, Sex ratio, Northern range limit, Extinctio

Zirconium-based metal–organic frameworks as acriflavine cargos in the battle against coronaviruses : a theoretical and experimental approach

[Image: see text] In this study, we present a complementary approach for obtaining an effective drug, based on acriflavine (ACF) and zirconium-based metal–organic frameworks (MOFs), against SARS-CoV-2. The experimental results showed that acriflavine inhibits the interaction between viral receptor-binding domain (RBD) of spike protein and angiotensin converting enzyme-2 (ACE2) host receptor driving viral cell entry. The prepared ACF@MOF composites exhibited low (MOF-808 and UiO-66) and high (UiO-67 and NU-1000) ACF loadings. The drug release profiles from prepared composites showed different release kinetics depending on the local pore environment. The long-term ACF release with the effective antiviral ACF concentration was observed for all studied ACF@MOF composites. The density functional theory (DFT) calculations allowed us to determine that π–π stacking together with electrostatic interaction plays an important role in acriflavine adsorption and release from ACF@MOF composites. The molecular docking results have shown that acriflavine interacts with several possible binding sites within the RBD and binding site at the RBD/ACE2 interface. The cytotoxicity and ecotoxicity results have confirmed that the prepared ACF@MOF composites may be considered potentially safe for living organisms. The complementary experimental and theoretical results presented in this study have confirmed that the ACF@MOF composites may be considered a potential candidate for the COVID-19 treatment, which makes them good candidates for clinical trials

Structures of pMV158 replication initiator RepB with and without DNA reveal a flexible dual-function protein

DNA replication is essential to all living organisms as it ensures the fidelity of genetic material for the next generation of dividing cells. One of the simplest replication initiation mechanisms is the rolling circle replication. In the streptococcal plasmid pMV158, which confers antibiotic resistance to tetracycline, replication initiation is catalysed by RepB protein. The RepB N-terminal domain or origin binding domain binds to the recognition sequence (bind locus) of the double-strand origin of replication and cleaves one DNA strand at a specific site within the nic locus. Using biochemical and crystallographic analyses, here we show how the origin binding domain recognises and binds to the bind locus using structural elements removed from the active site, namely the recognition α helix, and a β-strand that organises upon binding. A new hexameric structure of full-length RepB that highlights the great flexibility of this protein is presented, which could account for its ability to perform different tasks, namely bind to two distinct loci and cleave one strand of DNA at the plasmid origin.© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research

Defining a novel domain that provides an essential contribution to site-specific interaction of Rep protein with DNA

15 p.-6 fig.An essential feature of replication initiation proteins is their ability to bind to DNA. In this work, we describe a new domain that contributes to a replication initiator sequence-specific interaction with DNA. Applying biochemical assays and structure prediction methods coupled with DNA-protein crosslinking, mass spectrometry, and construction and analysis of mutant proteins, we identified that the replication initiator of the broad host range plasmid RK2, in addition to two winged helix domains, contains a third DNA-binding domain. The phylogenetic analysis revealed that the composition of this unique domain is typical within the described TrfA-like protein family. Both in vitro and in vivo experiments involving the constructed TrfA mutant proteins showed that the newly identified domain is essential for the formation of the protein complex with DNA, contributes to the avidity for interaction with DNA, and the replication activity of the initiator. The analysis of mutant proteins, each containing a single substitution, showed that each of the three domains composing TrfA is essential for the formation of the protein complex with DNA. Furthermore, the new domain, along with the winged helix domains, contributes to the sequence specificity of replication initiator interaction within the plasmid replication origin.National Science Centre [2012/04/A/NZ1/00048 to I.K.;2017/26/D/NZ1/00239 to K.W.]; Foundation for Polish Science [TEAM, POIR.04.04.00-00-5C75/17-00 to I.K.]; International Institute of Molecular and Cell Biology in Warsaw (to J.M.B.); Ministerio de Economía,Industria y Competitividad (MINECO/AEI) [BIO2012-30852, RTI2018-094549-B-I00 to R.G.]. Funding for open access charge: Foundation for Polish Science [TEAM,POIR.04.04.00-00-5C75/17-00].Peer reviewe

MUSiC : a model-unspecific search for new physics in proton-proton collisions at root s=13TeV

Results of the Model Unspecific Search in CMS (MUSiC), using proton-proton collision data recorded at the LHC at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1), are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches.Peer reviewe

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe