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The effect of climate change on avian offspring production: A global meta-analysis
Get PDFClimate change affects timing of reproduction in many bird species, but few studies have investigated its influence on annual reproductive output. Here, we assess changes in the annual production of young by female breeders in 201 populations of 104 bird species (N = 745,962 clutches) covering all continents between 1970 and 2019. Overall, average offspring production has declined in recent decades, but considerable differences were found among species and populations. A total of 56.7% of populations showed a declining trend in offspring production (significant in 17.4%), whereas 43.3% exhibited an increase (significant in 10.4%). The results show that climatic changes affect offspring production through compounded effects on ecological and life history traits of species. Migratory and larger-bodied species experienced reduced offspring production with increasing temperatures during the chick-rearing period, whereas smaller-bodied, sedentary species tended to produce more offspring. Likewise, multi-brooded species showed increased breeding success with increasing temperatures, whereas rising temperatures were unrelated to repro- ductive success in single-brooded species. Our study suggests that rapid declines in size of bird populations reported by many studies from different parts of the world are driven only to a small degree by changes in the production of young
SKI complex: A multifaceted cytoplasmic RNA exosome cofactor in mRNA metabolism with links to disease, developmental processes, and antiviral responses
Get PDFRNA stability and quality control are integral parts of gene expression regulation.
A key factor shaping eukaryotic transcriptomes, mainly via 30–50 exoribonucleolytic
trimming or degradation of diverse transcripts in nuclear and cytoplasmic compartments,
is the RNA exosome. Precise exosome targeting to various RNA molecules
requires strict collaboration with specialized auxiliary factors, which facilitate interactions
with its substrates. The predominant class of cytoplasmic RNA targeted by
the exosome are protein-coding transcripts, which are carefully scrutinized for
errors during translation. Normal, functional mRNAs are turned over following
protein synthesis by the exosome or by Xrn1 50–30-exonuclease, acting in concert
with Dcp1/2 decapping complex. In turn, aberrant transcripts are eliminated by
dedicated surveillance pathways, triggered whenever ribosome translocation is
impaired. Cytoplasmic 30–50 mRNA decay and surveillance are dependent on the
tight cooperation between the exosome and its evolutionary conserved co-factor—
the SKI (superkiller) complex (SKIc). Here, we summarize recent findings from
structural, biochemical, and functional studies of SKIc roles in controlling cytoplasmic
RNA metabolism, including links to various cellular processes. Mechanism of
SKIc action is illuminated by presentation of its spatial structure and details of its
interactions with exosome and ribosome. Furthermore, contribution of SKIc and
exosome to various mRNA decay pathways, usually converging on recycling of
ribosomal subunits, is delineated. A crucial physiological role of SKIc is emphasized
by describing association between its dysfunction and devastating human
disease—a trichohepatoenteric syndrome (THES). Eventually, we discuss SKIc
functions in the regulation of antiviral defense systems, cell signaling and developmental
transitions, emerging from interdisciplinary investigations
Proteome Profiling of the Dystrophic mdx Mice Diaphragm
Get PDFMdx mice with a spontaneous mutation in exon 23 of the Dmd gene represent the most common model to investigate the pathophysiology of Duchenne muscular dystrophy (DMD). The disease, caused by the lack of functional dystrophin, is characterized by irreversible impairment of muscle functions, with the diaphragm affected earlier and more severely than other skeletal muscles. We applied a label-free (LF) method and the more thorough tandem mass tag (TMT)-based method to analyze differentially expressed proteins in the diaphragm of 6-week-old mdx mice. The comparison of both methods revealed 88 commonly changed proteins. A more in-depth analysis of the TMT-based method showed 953 significantly changed proteins, with 867 increased and 86 decreased in dystrophic animals (q-value < 0.05, fold-change threshold: 1.5). Consequently, several dysregulated processes were demonstrated, including the immune response, fibrosis, translation, and programmed cell death. Interestingly, in the dystrophic diaphragm, we found a significant decrease in the expression of enzymes generating hydrogen sulfide (H2S), suggesting that alterations in the metabolism of this gaseous mediator could modulate DMD progression, which could be a potential target for pharmacological intervention
Diverse Partners of the Partitioning ParB Protein in Pseudomonas aeruginosa
Get PDFIn the majority of bacterial species, the tripartite ParAB-parS system, composed of an ATPase (ParA), a DNA-binding protein (ParB), and its target parS sequence(s), assists in the chromosome partitioning. ParB forms large nucleoprotein complexes at parS(s), located in the vicinity of origin of chromosomal replication (oriC), which after replication are subsequently positioned by ParA in cell poles. Remarkably, ParA and ParB participate not only in the chromosome segregation but through interactions with various cellular partners they are also involved in other cell cycle-related processes, in a species-specific manner. In this work, we characterized Pseudomonas aeruginosa ParB interactions with the cognate ParA, showing that the N-terminal motif of ParB is required for these interactions, and demonstrated that ParAB-parS-mediated rapid segregation of newly replicated ori domains prevented structural maintenance of chromosome (SMC)-mediated cohesion of sister chromosomes. Furthermore, using proteome-wide techniques, we have identified other ParB partners in P. aeruginosa, which encompass a number of proteins, including the nucleoid-associated proteins NdpA(PA3849) and NdpA2, MinE (PA3245) of Min system, and transcriptional regulators and various enzymes, e.g., CTP synthetase (PA3637). Among them are also NTPases PA4465, PA5028, PA3481, and FleN (PA1454), three of them displaying polar localization in bacterial cells. Overall, this work presents the spectrum of P. aeruginosa ParB partners and implicates the role of this protein in the cross-talk between chromosome segregation and other cellular processes
Occurrence of Dirofilaria repens in wild carnivores in Poland.
Get PDFDirofilaria repens is an expanding vector-borne zoonotic parasite of canines and other carnivores. Sub-clinically infected dogs constitute the most important reservoir of the parasite and the source of infection for its mosquito vectors. However, occurrence of D. repens infection in wild animals may contribute to the transmission of the parasite to humans and may explain the endemicity of filariae in newly invaded regions. The aim of the current study was to determine the occurrence of D. repens in 511 blood and spleen samples from seven species of wild carnivores (wolves, red foxes, Eurasian badgers, raccoons, raccoon dogs, stone martens, and pine martens) from different regions of Poland by means of a PCR protocol targeting the 12S rDNA gene. Dirofilaria repens–positive hosts were identified in seven of fourteen voivodeships in four of the seven regions of Poland: Masovia, Lesser Poland, Pomerania and Warmia-Masuria. The highest prevalence was found in Masovia region (8%), coinciding with the highest previously recorded prevalence in dogs in Central Poland. The DNA of Dirofilaria was detected in 16 samples of three species (total prevalence 3.13%). A low and similar percentage of positive samples (1.9%, 4.2% and 4.8%) was recorded among badgers, red foxes, and wolves, respectively. Dirofilaria repens–positive hosts were identified in seven of fourteen voivodships. Based on detection in different voivodeships, D. repens–positive animals were recorded in four out of the seven regions of Poland: in Masovia, Lesser Poland, Pomerania, and Warmia-Masuria. The highest prevalence of filariae was found in Masovia region (8%), reflecting the highest previously recorded prevalence in dogs (12–50%) in Central Poland. In summary, we conducted the first comprehensive study on the epidemiology of D. repens in seven species of wild hosts in all seven regions of Poland and identified the first case of D. repens infection in Eurasian badgers in Poland and the second in Europe
Exploring Extracellular Vesicles of Probiotic Yeast as Carriers of Biologically Active Molecules Transferred to Human Intestinal Cells
Get PDFExtracellular vesicles (EVs) are nanoparticles containing various bioactive cargos—e.g., proteins, RNAs, and lipids—that are released into the environment by all cell types. They are involved in, amongst other functions, intercellular communication. This article presents studies on EVs produced by the probiotic yeast Saccharomyces boulardii CNCM I-745. The size distribution and concentration of EVs in the liquid culture of yeast were estimated. Moreover, the vesicles of S. boulardii were tested for their cytotoxicity against three model human intestinal cell lines. This study did not show any significant negative effect of yeast EVs on these cells under tested conditions. In addition, EVs of S. boulardii were verified for their ability to internalize in vitro with human cells and transfer their cargo. The yeast vesicles were loaded with doxorubicin, an anticancer agent, and added to the cellular cultures. Subsequently, microscopic observations revealed that these EVs transferred the compound to human intestinal cell lines. A cytotoxicity test confirmed the activity of the transferred doxorubicin. Detailed information about the proteins present in EVs might be important in terms of exploring yeast EVs as carriers of active molecules. Thus, proteomic analysis of the EV content was also conducted within the present study, and it allowed the identification of 541 proteins after matching them to the Saccharomyces Genome Database (SGD). Altogether, this study provides strong evidence that the EVs of the probiotic CNCM I-745 strain could be considered a drug delivery system
Stability of Rad51 recombinase and persistence of Rad51 DNA repair foci depends on post-translational modifiers, ubiquitin and SUMO
Get PDFThe DNA double-strand breaks are particularly deleterious, especially when an error-free repair pathway is unavailable, enforcing the error-prone recombination pathways to repair the lesion. Cells can resume the cell cycle but at the expense of decreased viability due to genome rearrangements. One of the major players involved in recombinational repair of DNA damage is Rad51 recombinase, a protein responsible for presynaptic complex formation. We previously showed that an increased level of this protein promotes the usage of illegitimate recombination. Here we show that the level of Rad51 is regulated via the ubiquitin-dependent proteolytic pathway. The ubiquitination of Rad51 depends on multiple E3 enzymes, including SUMO-targeted ubiquitin ligases. We also demonstrate that Rad51 can be modified by both ubiquitin and SUMO. Moreover, its modification with ubiquitin may lead to opposite effects: degradation dependent on Rad6, Rad18, Slx8, Dia2, and the anaphase-promoting complex, or stabilization dependent on Rsp5. We also show that post-translational modifications with SUMO and ubiquitin affect Rad51's ability to form and disassemble DNA repair foci, respectively, influencing cell cycle progression and cell viability in genotoxic stress conditions. Our data suggest the existence of a complex E3 ligases network that regulates Rad51 recombinase's turnover, its molecular activity, and access to DNA, limiting it to the proportions optimal for the actual cell cycle stage and growth conditions, e.g., stress. Dysregulation of this network would result in a drop in cell viability due to uncontrolled genome rearrangement in the yeast cells. In mammals would promote the development of genetic diseases and cancer
Sex-dependent differences in behavioral and immunological responses to antibiotic and bacteriophage administration in mice
Get PDFIntroduction: The problem of antibiotic resistance is a global one, involving many industries and entailing huge financial outlays. Therefore, the search for alternative methods to combat drug-resistant bacteria has a priority status. Great potential is seen in bacteriophages which have the natural ability to kill bacterial cells. Bacteriophages also have several advantages over antibiotics. Firstly, they are considered ecologically safe (harmless to humans, plants and animals). Secondly, bacteriophages preparations are readily producible and easy to apply. However, before bacteriophages can be authorized for medical and veterinary use, they must be accurately characterized in vitro and in vivo to determinate safety.
Methods: Therefore, the aim of this study was to verify for the first time the behavioral and immunological responses of both male and female mice (C57BL/6J) to bacteriophage cocktail, composed of two bacteriophages, and to two commonly used antibiotics, enrofloxacin and tetracycline. Animal behavior, the percentage of lymphocyte populations and subpopulations, cytokine concentrations, blood hematological parameters, gastrointestinal microbiome analysis and the size of internal organs, were evaluated.
Results: Unexpectedly, we observed a sex-dependent, negative effect of antibiotic therapy, which not only involved the functioning of the immune system, but could also significantly impaired the activity of the central nervous system, as manifested by disruption of the behavioral pattern, especially exacerbated in females. In contrast to antibiotics, complex behavioral and immunological analyses confirmed the lack of adverse effects during the bacteriophage cocktail administration.
Discussion: The mechanism of the differences between males and females in appearance of adverse effects, related to the behavioral and immune functions, in the response to antibiotic treatment remains to be elucidated. One might imagine that differences in hormones and/or different permeability of the blood-brain barrier can be important factors, however, extensive studies are required to find the real reason(s)
Designing multi-target-directed flavonoids: a strategic approach to Alzheimer's disease
Get PDFThe underlying causes of Alzheimer's disease (AD) remain a mystery, with multiple pathological
components, including oxidative stress, acetylcholinesterase, amyloid-b, and metal ions, all playing
a role. Here we report a strategic approach to designing flavonoids that can effectively tackle multiple
pathological elements involved in AD. Our systematic investigations revealed key structural features for
flavonoids to simultaneously target and regulate pathogenic targets. Our findings led to the development
of a highly promising flavonoid that exhibits a range of functions, based on a complete structure–activity
relationship analysis. Furthermore, our mechanistic studies confirmed that this flavonoid's versatile
reactivities are driven by its redox potential and direct interactions with pathogenic factors. This work
highlights the potential of multi-target-directed flavonoids as a novel solution in the fight against AD
Efficient, robust, and versatile fluctuation data analysis using MLE MUtation Rate calculator (mlemur)
Get PDFThe fluctuation assay remains an important tool for analyzing the levels of mutagenesis in microbial populations. The mutant counts originating from some average number of mutations are usually assumed to obey the Luria–Delbrück distribution. While several tools for estimating mutation rates are available, they sometimes lack accuracy or versatility under non-standard conditions. In this work, extensions to the Luria–Delbrück protocol to account for phenotypic lag and cellular death with either perfect or partial plating were developed. Hence, the novel MLE MUtation Rate calculator, or mlemur, is the first tool that provides a user-friendly graphical interface allowing the researchers to model their data with consideration for partial plating, differential growth of mutants and non-mutants, phenotypic lag, cellular death, variability of the final number of cells, post-exponential-phase mutations, and the size of the inoculum. Additionally, mlemur allows the users to incorporate most of these special conditions at the same time to obtain highly accurate estimates of mutation rates and P values, confidence intervals for an arbitrary function of data (such as fold), and perform power analysis and sample size determination for the likelihood ratio test. The accuracy of point and interval estimates produced by mlemur against historical and simulated fluctuation experiments are assessed. Both mlemur and the analyses in this work might be of great help when evaluating fluctuation experiments and increase the awareness of the limitations of the widely-used Lea–Coulson formulation of the Luria–Delbrück distribution in the more realistic biological contexts