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Pygoscelid penguins breeding distribution and population trends at Lions Rump rookery, King George Island
Get PDFAbstract: Long term changes (46 years) in the abundance of pygoscelid penguins breeding
populations and nests distribution in the Lions Rump (King George Island) colony were in−
vestigated in three time intervals, according to previously published two censuses and one
original study conducted in 2010. At that time a detailed colony map based on the GIS system
was made. Results of this study showed different trends for each investigated species. In the
last three decades Adélie penguin breeding populations showed strong declining tendencies
(69.61%). In contrast, the population of gentoo penguins represents the reverse trend, increas−
ing 171.85% over the same period. Observed changes in both penguin population sizes are re−
flected in the different spatial and geographic distribution of their nests. The population
changes observed at the Lions Rump colony are consistent with the relevant pygoscelid pen−
guin tendencies in the western Antarctic Peninsula region. Breeding penguin population dy−
namics at Lions Rump area with a minimal disturbance by human activity may well illustrate
a natural response of those birds to environmental changes in the Antarctic
Application of supercritical CO2 for extraction of polyisoprenoid alcohols and their esters from plant tissues
Get PDFThe spirit of competition: to win or not to win.
Get PDFA competition is a contest between individuals or groups. The gain is often an award or recognition, which serves as a catalyst to motivate individuals to put forth their very best. Such events for recognition and success are part of many International Society for Computational Biology (ISCB) Student Council Regional Student Groups (RSGs) activities. These include a popular science article contest, a Wikipedia article competition, travel grants, poster and oral presentation awards during conferences, and quizzes at social events. Organizing competitions is no different than any other event; they require a lot of hard work to be successful. Each event gives remarkable organizational and social experience for students running it, while at the same time the participants of the competitions are rewarded by prizes and recognition. It gives everybody involved an opportunity to demonstrate their extraordinary talents and skills. Competitions are unique because they bring out both the best and worst in people
Factors and processes modulating phenotypes in neuronopathic lysosomal storage diseases
Get PDFLysosomal storage diseases are inherited metabolic disorders caused by genetic defects causing deficiency of various lysosomal proteins, and resultant accumulation of non-degraded compounds. They are multisystemic diseases, and in most of them (>70 %) severe brain dysfunctions are evident. However, expression of various phenotypes in particular diseases is extremely variable, from non-neuronopathic to severely neurodegenerative in the deficiency of the same enzyme. Although all lysosomal storage diseases are monogenic, clear genotype-phenotype correlations occur only in some cases. In this article, we present an overview on various factors and processes, both general and specific for certain disorders, that can significantly modulate expression of phenotypes in these diseases. On the basis of recent reports describing studies on both animal models and clinical data, we propose a hypothesis that efficiency of production of compounds that cannot be degraded due to enzyme deficiency might be especially important in modulation of phenotypes of patients suffering from lysosomal storage diseases
Human mitochondrial RNA decay mediated by PNPase-hSuv3 complex takes place in distinct foci.
Get PDFRNA decay is usually mediated by protein complexes and can occur in specific foci such as P-bodies in the cytoplasm of eukaryotes. In human mitochondria nothing is known about the spatial organization of the RNA decay machinery, and the ribonuclease responsible for RNA degradation has not been identified. We demonstrate that silencing of human polynucleotide phosphorylase (PNPase) causes accumulation of RNA decay intermediates and increases the half-life of mitochondrial transcripts. A combination of fluorescence lifetime imaging microscopy with Förster resonance energy transfer and bimolecular fluorescence complementation (BiFC) experiments prove that PNPase and hSuv3 helicase (Suv3, hSuv3p and SUPV3L1) form the RNA-degrading complex in vivo in human mitochondria. This complex, referred to as the degradosome, is formed only in specific foci (named D-foci), which co-localize with mitochondrial RNA and nucleoids. Notably, interaction between PNPase and hSuv3 is essential for efficient mitochondrial RNA degradation. This provides indirect evidence that degradosome-dependent mitochondrial RNA decay takes place in foci
Efficient, non-toxic gene delivery by negatively charged polyprenyl-based lipoplexes: Application in RNA delivery and the effects on cell physiology
Get PDFThe development in the field of DNA and RNA delivery into cells and progress in understanding pathogenesis
of many diseases resulted in nucleic acids becoming actually drugs and their delivery one of the top molecular
biology techniques applicable in clinics. Still, one of the major challenges facing the development of gene
therapy is lack of efficient and safe gene vectors.
We have examined a new class of polyprenyl-based cationic lipids for gene transfer. Studies have shown that
semisynthetic polyprenyltrimethylammonium iodides (PTAI) in formulations with co-lipids (DOPE,
DC-cholesterol, DOPC) have the ability to effectively transfect plasmid DNA in a wide range of cell types in
vitro both in the presence and absence of serum. Although generally it is considered that bigger lipoplexes
bearing positive zeta potential are more efficient, our data clearly demonstrate that small (90 – 150 nm),
negatively charged (about -30 mV) polyprenyl-based lipoplexes are efficient and have parameters making
them promising candidates for in vivo gene delivery.
As it was demonstrated that lipofection procedure may have several side effects on cell physiology, we tested
the effects of PTAI formulation on cell motility, proliferation, viability and gap junctional intercellular coupling
(GJIC). We have tested four derivatives: amino-Pren-7, amino-Pren-8, amino-Pren-11 and amino-Pren-15.
Cell motility of a model DU-145 (human prostate cancer) cells was estimated by time-laps monitoring of
movement of individual cells and GJIC intensity measured using donor cells labelled with calcein plated onto
monolayers of acceptor cells transfected with PTAI-based lipoplexes. The dynamics of calcein transfer from
donor to acceptor cells was analyzed. Antimicrobial activity was evaluated by colony reduction assay and the
hemolytic activity against human red blood cells (RBCs) was tested using PBS suspension prepared from
fresh blood.
The results show that lipoplexes based on PTAI have no effects on cell physiology that is cell viability,
proliferation and morphology. Moreover, they also occurred to have no effect on GJIC and cell motility (24
hours after transfection all the cells cover the distance of about 210-240 μm showing a displacement of 70-80
μm). Some PTAI-based vectors exhibit potent bactericidal activity against Streptococcus aureus and
Escherichia coli, while showing no toxic effect on eukaryotic cells, which can be beneficial during prolonged
storage of formulations. Furthermore, (as we suggest in vivo application of PTAI vectors) we have also
proved their safety towards human RBSs, which membranes are not disrupted in the presence of all the
examined concentrations of PTAI-based lipoplexes. Moreover, the formulations tested in plasmid DNA transfer
into cells are also effective in gene silencing techniques utilizing RNA delivery. We have successfully introduced
shRNA inducing GFP gene silencing into DU145, XC (rat sarcoma) and B16F10 (mouse melanoma) cells
expressing pEGFP-C1 plasmid achieving GFP gene silencing. Additionally, PTAI-based formulations can be
safely stored for extended periods (up to 18 months) at 4°C.
In conclusion, lipoplexes based on PTAI provide ability to introduce DNA or RNA into cells with satisfying
efficiency, easily and safety, as they exhibit no toxic activity and no side effects on cell proliferation, motility
and GJIC. What is more, PTAI-based formulations show advantages important for convenient use (both –
DNA and RNA delivery, antimicrobial activity, prolonged storage) and in vivo applications (no RBCs rupture in
the presence of PTAI-based lipoplexes, effectiveness in the presence of serum)
Expanding the phenotype associated with missense mutations of the ARX gene.
No full textThe Aristaless-related homeobox gene (ARX, OMIM# 300382)located in chromosome Xp21.3 belongs to a family of homeobox genes that encode transcription factors playing a crucial role during early embryogenesis. In the brain, ARX is involved in cerebral development and patterning. Mutations in ARX have been shown to cause different forms of intellectual disability, which are classified as a malformation and a nonmalformation group of phenotypes.
The latter involves mainly expansions of the trinucleotide repeats coding the second and first polyalanine tracts (polyA). Only few missense mutations in ARX have been reported in nonmalformed patients to date [Shoubridge et al., 2010; Sartori et al., 2011]. Here, we report on a large family with recurrence of intellectual disability and dystonia due to a novel missense mutation in ARX. There were nine affected males over two generations and there was
an X-linked pattern of inheritance (Fig. 1). Patient cognitive and social skills were assessed by means of the Wechsler Intelligence Scale for Children (WISC-R) and Edgar Doll’s Vineland Social Maturity Scale (VSMS
Novel A18T and pA29S substitutions in α-synuclein may be associated with sporadic Parkinson's disease.
No full textMutations in the α-synuclein-encoding gene SNCA are considered as a rare cause of Parkinson's disease (PD). Our objective was to examine the frequency of the SNCA point mutations among PD patients of Polish origin
Uracil in duplex DNA is a substrate for the human nucleotide incision repair pathway
Get PDFSpontaneous hydrolytic deamination of cytosine to uracil (U) in DNA is a constant source of genome instability in cells. This mutagenic process is greatly enhanced at high temperatures and in single-stranded DNA. If not repaired, these uracil residues give rise to C→T transitions, which are the most common spontaneous mutations occurring in living organisms, and are frequently found in human tumours. In the majority of species, uracil residues are removed from DNA by specific uracil-DNA glycosylases in the base excision repair (BER) pathway. Alternatively, in certain archaeal organisms uracil residues are eliminated by apurinic/apyrimidinic (AP) endonucleases in the nucleotide incision repair (NIR) pathway. Here, we characterized the substrate specificity of the major human AP endonuclease 1, APE1, towards U in duplex DNA. APE1 cleaves oligonucleotide duplexes containing a single U•G base pair; this activity depends strongly on the sequence context and the base opposite to U. The apparent kinetic parameters of the reactions show that APE1 has high affinity for DNA containing U but cleaves the DNA duplex at an extremely low rate. MALDI-TOF MS analysis of the reaction products demonstrated that APE1-catalyzed cleavage of an U•G duplex generates the expected DNA fragments containing a 5'-terminal deoxyuridine monophosphate. The fact that U in duplex DNA is recognized and cleaved by APE1 in vitro suggests that this property of exonuclease III family of AP endonucleases is remarkably conserved from Archaea to human. We propose that NIR may act as a backup pathway to BER to remove uracils arising from cytosine deamination
Maf1, a general negative regulator of RNA polymerase III in yeast
Get PDFtRNA synthesis by yeast RNA polymerase III (Pol III) is down-regulated under growth-limiting conditions. This control is mediated by Maf1, a global negative regulator of Pol III transcription. Conserved from yeast to man, Maf1 was originally discovered in Saccharomyces cerevisiae by a genetic approach. Details regarding the molecular basis of Pol III repression by Maf1 are now emerging from the recently reported structural and biochemical data on Pol III and Maf1. The phosphorylation status of Maf1 determines its nuclear localization and interaction with the Pol III complex and several Maf1 kinases have been identified to be involved in Pol III control. Moreover, Maf1 indirectly affects tRNA maturation and decay. Here I discuss the current understanding of the mechanisms that oversee the Maf1-mediated regulation of Pol III activity and the role of Maf1 in the control of tRNA biosynthesis in yeast. This article is part of a Special Issue entitled: Transcription by Odd Pols