Publications by authors named "Jelena Aleksic"

30 Publications

  • Page 1 of 1

TReND in Africa: Toward a Truly Global (Neuro)science Community.

Neuron 2020 08 20;107(3):412-416. Epub 2020 Jul 20.

TReND in Africa, Brighton, UK; The Francis Crick Institute, London, UK. Electronic address:

TReND is a volunteer-scientist run charity dedicated to promoting research and education on the African continent. Focusing on neuroscience, we discuss approaches to address some of the factors that currently stifle Africa's scientific development and our experience in implementing them.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuron.2020.06.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370902PMC
August 2020

Capillaria plica in Red Foxes (Vulpes vulpes) from Serbia: Epidemiology and Diagnostic Approaches to Urinary Capillariosis in Domestic Carnivores.

Acta Parasitol 2020 Dec 29;65(4):954-962. Epub 2020 Jun 29.

Department of Parasitology, Faculty of Veterinary Medicine, University of Belgrade, Beograd, Serbia.

Purpose: This study aimed to determine the presence of C. plica in red foxes and to point out the possibilities of different diagnostic methods, that could be used for diagnosis of urinary capillariosis in domestic carnivores.

Methods: Seventeen red foxes from hunting grounds in the Kolubara District, Republic of Serbia, were examined in February 2019. Animals to be shot were selected based on the criteria of gamekeepers and the permission of the competent Ministry. After hunting, the foxes were examined by ultrasound and autopsied. After the necropsy, biochemical and sediment analysis of urine morphological identification of isolated adult parasites, and macroscopic/microscopic examination of the urinary bladder and kidney tissue were performed.

Results: Adults of C. plica were detected in 3/17 foxes (17.6%) by ultrasound imaging and in 6/17 foxes (35.3%) by necropsy examination. Parasite eggs were found in the urinary sediment of 9/17 foxes (52.9%). The predominant histopathologic changes were amyloid degeneration of the renal glomeruli and proximal tubules (8/17 foxes-47%) as well as acute cystitis (7/17 foxes-41.2%). The occurrence of C. plica was determined in 12/17 (70.6%) of the examined foxes.

Discussion: This study is the first record of the C. plica in red foxes in the Republic of Serbia. Diagnostic methods used in this study could make possible the early revealing of capillariosis in domestic carnivores and could provide reliable clinical and parasitological screening of suspect animals.

Conclusion: The study presents the first report of urinary capillariosis in a fox population in Serbia. The established high prevalence of C. plica in foxes could presume its higher prevalence in domestic and wild carnivores in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11686-020-00244-9DOI Listing
December 2020

Complete mitogenome data for the Serbian population: the contribution to high-quality forensic databases.

Int J Legal Med 2020 Sep 6;134(5):1581-1590. Epub 2020 Jun 6.

Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, PO Box 23, Vojvode Stepe 444a, Belgrade, 11010, Serbia.

Mitochondrial genome (mtDNA) is a valuable resource in resolving various human forensic casework. The usage of variability of complete mtDNA genomes increases their discriminatory power to the maximum and enables ultimate resolution of distinct maternal lineages. However, their wider employment in forensic casework is nowadays limited by the lack of appropriate reference database. In order to fill in the gap in the reference data, which, considering Slavic-speaking populations, currently comprises only mitogenomes of East and West Slavs, we present mitogenome data for 226 Serbians, representatives of South Slavs from the Balkan Peninsula. We found 143 (sub)haplogroups among which West Eurasian ones were dominant. The percentage of unique haplotypes was 85%, and the random match probability was as low as 0.53%. We support previous findings on both high levels of genetic diversity in the Serbian population and patterns of genetic differentiation among this and ten studied European populations. However, our high-resolution data supported more pronounced genetic differentiation among Serbians and two Slavic populations (Russians and Poles) as well as expansion of the Serbian population after the Last Glacial Maximum and during the Migration period (fourth to ninth century A.D.), as inferred from the Bayesian skyline analysis. Phylogenetic analysis of haplotypes found in Serbians contributed towards the improvement of the worldwide mtDNA phylogeny, which is essential for the interpretation of the mtDNA casework.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00414-020-02324-xDOI Listing
September 2020

Comparison of Three Ratiometric Temperature Readings from the Er Upconversion Emission.

Nanomaterials (Basel) 2020 Mar 28;10(4). Epub 2020 Mar 28.

Vinča Institute of Nuclear Sciences, University of Belgrade, P.O. Box 522, 11001 Belgrade, Serbia.

The emission of Er provides three combinations of emission bands suitable for ratiometric luminescence thermometry. Two combinations utilize ratios of visible emissions (H→I at 523 nm/ S→I at 542 nm and F→I at 485 nm/ S→I at 545 nm), while emissions from the third combination are located in near-infrared, e.g., in the first biological window (H→I at 793 nm/ S→I at 840 nm). Herein, we aimed to compare thermometric performances of these three different ratiometric readouts on account of their relative sensitivities, resolutions, and repeatability of measurements. For this aim, we prepared Yb,Er:YF nanopowders by oxide fluorination. The structure of the materials was confirmed by X-ray diffraction analysis and particle morphology was evaluated from FE-SEM measurements. Upconversion emission spectra were measured over the 293-473 K range upon excitation by 980 nm radiation. The obtained relative sensitivities on temperature for 523/542, 485/542, and 793/840 emission intensity ratios were 1.06 ± 0.02, 2.03 ± 0.23, and 0.98 ± 0.10%K with temperature resolutions of 0.3, 0.7, and 1.8 K, respectively. The study showed that the higher relative temperature sensitivity does not necessarily lead to the more precise temperature measurement and better resolution, since it may be compromised by a larger uncertainty in measurement of low-intensity emission bands.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nano10040627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221525PMC
March 2020

Banat donkey, a neglected donkey breed from the central Balkans (Serbia).

PeerJ 2020 3;8:e8598. Epub 2020 Mar 3.

Department of Biology, Faculty of Veterinary Medicine, University of Belgrade, Belgrade, Serbia.

The dominant donkey breed in the Balkans is the mid-sized Balkan donkey with a grey to chocolate coat color. Local breeders from Serbia, however, still maintain a few larger individuals of a lighter coat color, named Banat donkey, and speculate that they are descendants of a Spanish donkey heard that had been transferred to the Banat region by the Hapsburg Queen Maria Theresa in the XVIII century for a specific purpose, to work in local vineyards. We have previously found a unique nuclear gene-pool and a prevalence of mitochondrial Clade 2 haplotypes in several such animals. In this study, we: (i) perform a comparative analysis of 18 morphological traits of the Banat donkey (seven individuals), Balkan donkey (53 individuals from two sub-populations of this breed) and the potential hybrids (eight individuals), and demonstrate the morphological distinctiveness of the Banat donkey, highlighting the diagnostic traits for distinguishing the breed: hip height, croup width, body length and chest depth; (ii) re-analyse published nuclear microsatellite data for these groups, and reveal that, although severely depopulated, the genetically distinct Banat donkey is not severely affected by the loss of genetic diversity and inbreeding; (iii) demonstrate that previously published Banat donkey mitochondrial haplotypes, analyzed genealogically together with those reported in ancient and modern individuals from Spain, Italy, Turkey, Cyprus and Africa, are shared with three Spanish breeds and individuals belonging to Amiata and some other Italian breeds. A unique morphological feature present in Banat and Somali wild donkeys, but also in Amiata donkeys, black stripes on legs, suggests that the origin of Clade 2 donkeys may be much more complex than previously thought. Actions to preserve the Banat donkey, a valuable but critically endangered genetic resource (<100 individuals), are urgent.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7717/peerj.8598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059758PMC
March 2020

Genomic data provide new insights on the demographic history and the extent of recent material transfers in Norway spruce.

Evol Appl 2019 Sep 30;12(8):1539-1551. Epub 2019 Apr 30.

Department of Ecology and Genetics, Evolutionary Biology Centre Uppsala University Uppsala Sweden.

Primeval forests are today exceedingly rare in Europe, and transfer of forest reproductive material for afforestation and improvement has been very common, especially over the last two centuries. This can be a serious impediment when inferring past population movements in response to past climate changes such as the last glacial maximum (LGM), some 18,000 years ago. In the present study, we genotyped 1,672 individuals from three species (, , and ) at 400K SNPs using exome capture to infer the past demographic history of Norway spruce () and estimate the amount of recent introduction used to establish the Norway spruce breeding program in southern Sweden. Most of these trees belong to and originate from the base populations of the Swedish breeding program. Others originate from populations across the natural ranges of the three species. Of the 1,499 individuals stemming from the breeding program, a large proportion corresponds to recent introductions from mainland Europe. The split of occurred 23 million years ago (mya), while the divergence between and began 17.6 mya. Demographic inferences retrieved the same main clusters within than previous studies, that is, a vast northern domain ranging from Norway to central Russia, where the species is progressively replaced by Siberian spruce () and two smaller domains, an Alpine domain and a Carpathian one, but also revealed further subdivision and gene flow among clusters. The three main domains divergence was ancient (15 mya), and all three went through a bottleneck corresponding to the LGM. Approximately 17% of Nordic domain migrated from ~103K years ago, when both species had much larger effective population sizes. Our analysis of genomewide polymorphism data thus revealed the complex demographic history of Picea genus in Western Europe and highlighted the importance of material transfer in Swedish breeding program.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/eva.12801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6708423PMC
September 2019

Importance of Parasitological Screening in Extensive Poultry Farming Based on Organic Production.

Acta Parasitol 2019 Jun 2;64(2):336-346. Epub 2019 Apr 2.

Department of Parasitology, Faculty of Veterinary Medicine, University of Belgrade, Belgrade, Serbia.

Introduction: Timely and valid diagnostic of parasitic diseases are prerequisites for profitable traditional poultry breeding, which enables adequate prophylaxis and effective therapy. This research is retrospective of the prevalence of endoparasites in 880 hens, 291 ducks, 171 geese and 302 turkeys in extensive poultry breeding in the Republic of Serbia.

Materials And Methods: Qualitative parasitological examination was done by conventional gravitational flotation method and sedimentation method. In rare cases of animal death, an autopsy was performed.

Results: In the period from 2012 to 2017, in 12 examined localities in the Republic of Serbia, single or mixed infections with endoparasites Eimeria spp., Ascaridia galli, Heterakis gallinarum, Capillaria contorta, Amidostomum anseris and Syngamus trachea were diagnosed. The highest prevalence of ascaridiosis was detected in hens (15.69-24.05%), trichostrongylidosis in ducks (20.53-30.19%), heterakiosis (20.89- 25.86%) and capillariosis (20.68-26.08%) in geese, and syngamosis (23.39%) and capillariosis (14.28- 24.17%) in turkeys. Endoparasites were the most prevalent in hens in south Serbia (63.21%), in ducks in central Serbia (54.71%) and in geese (46.55%) and turkeys (58.24%) in north Serbia. Among mixed infections predominant was polyparasitism of Heterakis spp. and Capillaria spp.

Conclusions: An epizootiological and clinical diagnostic approach based on the results of parasitological screening is very important from the aspect of organic poultry farming.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2478/s11686-019-00042-yDOI Listing
June 2019

Honey bee viruses in Serbian colonies of different strength.

PeerJ 2018 14;6:e5887. Epub 2018 Nov 14.

Department of Biology, Faculty of Veterinary Medicine, University of Belgrade, Belgrade, Serbia.

Protection of honey bees is of great economic importance because of their role in pollination. Crucial steps towards this goal are epidemiological surveys of pathogens connected with honey bee losses. In this study deformed wing virus (DWV), chronic bee paralysis virus (CBPV), acute bee paralysis virus (ABPV) and sacbrood virus (SBV) were investigated in colonies of different strength located in five regions of Serbia. The relationship between colony strength and virus occurrence/infection intensity were assessed as well as the genetic relationship between virus sequences from Serbia and worldwide. Real-time RT-PCR analyses detected at least one virus in 87.33% of colonies. Single infection was found in 28.67% colonies (21.33%, 4.00%, 2.67% and 0.67% in cases of DWV, ABPV, SBV and CBPV, respectively). In the majority of colonies (58.66%) more than one virus was found. The most prevalent was DWV (74%), followed by ABPV, SBV and CBPV (49.30%, 24.00% and 6.70%, respectively). Except for DWV, the prevalence of the remaining three viruses significantly varied between the regions. No significant differences were found between colony strength and either (i) the prevalence of DWV, ABPV, SBV, CBPV and their combinations, or (ii) DWV infection levels. The sequences of honey bee viruses obtained from bees in Serbia were 93-99% identical with those deposited in GenBank.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7717/peerj.5887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240340PMC
November 2018

Capture the vertebral fracture: Risk factors as a prediction.

J Back Musculoskelet Rehabil 2019 ;32(2):269-276

University of Novi Sad, Faculty of Medicine Novi Sad, Serbia.

Objective: Vertebral fractures are the most common osteoporotic fractures occurring due to low bone mineral density, as well as other risk factors. The aim of the paper is to investigate risk factors for vertebral osteoporotic fracture occurrence in postmenopausal women.

Methods: Retrospective analysis of data pertaining to 651 postmenopausal women obtained from the National Osteoporosis Registry of Serbia was conducted. Further analyses were performed on 217 osteoporotic women identified from those records, whereby those in the experimental group (n= 110) had a vertebral fracture, while those assigned to the control group (n= 107) did not. The two groups were comparable in terms of age (t= 0.450; p> 0.01). Risk factors that could serve as the best predictors of vertebral fracture occurrence were investigated. Multivariate logistic regression analysis was used for testing effect of several factors on vertebral fracture occurrence as the dependent variable.

Results: Patients that have never suffered a vertebral fracture had a significantly higher bone mineral density (t= 8.161; p< 0.01) in comparison to those with a verified vertebral fracture. Factors that significantly contributed to the risk of vertebral fracture were presence of kyphosis (OR 708.338; 95% CI 19.238-26.081.950), use of glucocorticoids (OR 87.618; 95% CI 9.175-836.707), and presence of comorbidities (OR 7.327; 95% CI 1.500-35.793). Moreover, a unit increase in body mass index (BMI) was found to lower the probability of vertebral fracture by a factor of 0.846. Women that entered menopause later have lower chance of suffering a vertebral fracture (OR = 0.539; 95% CI 0.400-0.726).

Conclusion: Lower body mass index, presence of kyphosis, use of glucocorticoids, early menopause onset, and presence of comorbidities are the factors that contribute the most to vertebral osteoporotic fracture occurrence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/BMR-170898DOI Listing
May 2019

Cross-cultural validation of the Modified Falls Efficacy Scale in Serbian community-dwelling women at risk for osteoporotic fracture.

Menopause 2018 04;25(4):444-450

Institute for Epidemiology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.

Objective: Cross-cultural validation of the Serbian version of the Modified Falls Efficacy Scale (MFES).

Methods: This cross-sectional study involved 257 women aged 65 years and above who were referred for dual-energy x-ray absorptiometry examination at the Railway Healthcare Institute in Belgrade, Serbia, between January and April 2016. Data collection comprised of a sociodemographic questionnaire and Geriatric Depression Scale-Short Form (GDS-SF) questionnaire, and data related to fractures, level of physical activity, use of medications that can increase the risk of falls, and frequency of falls in the past 12 months. None of the study participants had been previously treated for osteoporosis. The internal consistency of the questionnaire items was assessed via Cronbach's alpha, whereas the interclass correlation coefficient (ICC) was used to calculate test-retest reliability based on the sample of 257 women. We also evaluated concurrent, convergent, and construct validity.

Results: Cronbach's alpha for the total assay score was 0.98. Correlations among the items ranged from 0.84 to 0.93. While ICC for the scale as a whole was 0.99 (95% confidence interval 0.98-0.99), ICC pertaining to individual items ranged from 0.82 to 0.99. Concurrent validity analysis revealed a significant positive correlation between MFES scores and the reported level of physical activity (ρ = 0.34; P < 0.01). Convergent validity was tested through the ratio of MFES and sociodemographic variables. The findings indicated presence of a significant negative correlation between the MFES scores and age (ρ = -0.32; P < 0.01), age of menopause onset (ρ = -0.16; P = 0.01), and GDS-SF scores (ρ = -0.12; P = 0.04), and positive correlation between MFES and the level of social activity (ρ = 0.22; P < 0.01). Significant differences were noted between the MFES scores of participants who had no history fractures and those who did (U = 5277.50; P < 0.01), and between scores of women who reported falling in the past 12 months and those who did not (U = 4968.50; P < 0.01). Similarly, significant differences (P < 0.01) in the scores pertaining to each MFES item were observed between women who had experienced falls in the past (n = 101) and those who had not (n = 156).

Conclusion: The Serbian version of the MFES is a reliable and valid instrument that can be used in both clinical practice and research to describe and measure self-perceived fear of falling in older individuals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/GME.0000000000001009DOI Listing
April 2018

Mitochondrial super-haplogroup U diversity in Serbians.

Ann Hum Biol 2017 Aug 19;44(5):408-418. Epub 2017 Feb 19.

a Institute of Molecular Genetics and Genetic Engineering , University of Belgrade , Belgrade , Serbia.

Background: Available mitochondrial (mtDNA) data demonstrate genetic differentiation among South Slavs inhabiting the Balkan Peninsula. However, their resolution is insufficient to elucidate the female-specific aspects of the genetic history of South Slavs, including the genetic impact of various migrations which were rather common within the Balkans, a region having a turbulent demographic history.

Aim: The aim was to thoroughly study complete mitogenomes of Serbians, a population linking westward and eastward South Slavs.

Subjects And Methods: Forty-six predominantly Serbian super-haplogroup U complete mitogenomes were analysed phylogenetically against ∼4000 available complete mtDNAs of modern and ancient Western Eurasians.

Results: Serbians share a number of U mtDNA lineages with Southern, Eastern-Central and North-Western Europeans. Putative Balkan-specific lineages (e.g. U1a1c2, U4c1b1, U5b3j, K1a4l and K1a13a1) and lineages shared among Serbians (South Slavs) and West and East Slavs were detected (e.g. U2e1b1, U2e2a1d, U4a2a, U4a2c, U4a2g1, U4d2b and U5b1a1).

Conclusion: The exceptional diversity of maternal lineages found in Serbians may be associated with the genetic impact of both autochthonous pre-Slavic Balkan populations whose mtDNA gene pool was affected by migrations of various populations over time (e.g. Bronze Age pastoralists) and Slavic and Germanic newcomers in the early Middle Ages.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/03014460.2017.1287954DOI Listing
August 2017

Stem cell function and stress response are controlled by protein synthesis.

Nature 2016 06;534(7607):335-40

Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, Department of Genetics, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.

Whether protein synthesis and cellular stress response pathways interact to control stem cell function is currently unknown. Here we show that mouse skin stem cells synthesize less protein than their immediate progenitors in vivo, even when forced to proliferate. Our analyses reveal that activation of stress response pathways drives both a global reduction of protein synthesis and altered translational programmes that together promote stem cell functions and tumorigenesis. Mechanistically, we show that inhibition of post-transcriptional cytosine-5 methylation locks tumour-initiating cells in this distinct translational inhibition programme. Paradoxically, this inhibition renders stem cells hypersensitive to cytotoxic stress, as tumour regeneration after treatment with 5-fluorouracil is blocked. Thus, stem cells must revoke translation inhibition pathways to regenerate a tissue or tumour.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/nature18282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5040503PMC
June 2016

Neurogenomics: An opportunity to integrate neuroscience, genomics and bioinformatics research in Africa.

Appl Transl Genom 2015 Jun 22;5:3-10. Epub 2015 Jul 22.

Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 1QR, United Kingdom.

Modern genomic approaches have made enormous contributions to improving our understanding of the function, development and evolution of the nervous system, and the diversity within and between species. However, most of these research advances have been recorded in countries with advanced scientific resources and funding support systems. On the contrary, little is known about, for example, the possible interplay between different genes, non-coding elements and environmental factors in modulating neurological diseases among populations in low-income countries, including many African countries. The unique ancestry of African populations suggests that improved inclusion of these populations in neuroscience-related genomic studies would significantly help to identify novel factors that might shape the future of neuroscience research and neurological healthcare. This perspective is strongly supported by the recent identification that diseased individuals and their kindred from specific sub-Saharan African populations lack common neurological disease-associated genetic mutations. This indicates that there may be population-specific causes of neurological diseases, necessitating further investigations into the contribution of additional, presently-unknown genomic factors. Here, we discuss how the development of neurogenomics research in Africa would help to elucidate disease-related genomic variants, and also provide a good basis to develop more effective therapies. Furthermore, neurogenomics would harness African scientists' expertise in neuroscience, genomics and bioinformatics to extend our understanding of the neural basis of behaviour, development and evolution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.atg.2015.06.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4745356PMC
June 2015

An open science peer review oath.

F1000Res 2014 12;3:271. Epub 2014 Nov 12.

School of Biological and Chemical Sciences, Queen Mary University of London, London, UK.

One of the foundations of the scientific method is to be able to reproduce experiments and corroborate the results of research that has been done before. However, with the increasing complexities of new technologies and techniques, coupled with the specialisation of experiments, reproducing research findings has become a growing challenge. Clearly, scientific methods must be conveyed succinctly, and with clarity and rigour, in order for research to be reproducible. Here, we propose steps to help increase the transparency of the scientific method and the reproducibility of research results: specifically, we introduce a peer-review oath and accompanying manifesto. These have been designed to offer guidelines to enable reviewers (with the minimum friction or bias) to follow and apply open science principles, and support the ideas of transparency, reproducibility and ultimately greater societal impact. Introducing the oath and manifesto at the stage of peer review will help to check that the research being published includes everything that other researchers would need to successfully repeat the work. Peer review is the lynchpin of the publishing system: encouraging the community to consciously (and conscientiously) uphold these principles should help to improve published papers, increase confidence in the reproducibility of the work and, ultimately, provide strategic benefits to authors and their institutions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4304228PMC
http://dx.doi.org/10.12688/f1000research.5686.2DOI Listing
February 2015

Mitochondrial DNA perspective of Serbian genetic diversity.

Am J Phys Anthropol 2015 Mar 24;156(3):449-65. Epub 2014 Nov 24.

Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, 11010, Belgrade, Serbia.

Although south-Slavic populations have been studied to date from various aspects, the population of Serbia, occupying the central part of the Balkan Peninsula, is still genetically understudied at least at the level of mitochondrial DNA (mtDNA) variation. We analyzed polymorphisms of the first and the second mtDNA hypervariable segments (HVS-I and HVS-II) and informative coding-region markers in 139 Serbians to shed more light on their mtDNA variability, and used available data on other Slavic and neighboring non-Slavic populations to assess their interrelations in a broader European context. The contemporary Serbian mtDNA profile is consistent with the general European maternal landscape having a substantial proportion of shared haplotypes with eastern, central, and southern European populations. Serbian population was characterized as an important link between easternmost and westernmost south-Slavic populations due to the observed lack of genetic differentiation with all other south-Slavic populations and its geographical positioning within the Balkan Peninsula. An increased heterogeneity of south Slavs, most likely mirroring turbulent demographic events within the Balkan Peninsula over time (i.e., frequent admixture and differential introgression of various gene pools), and a marked geographical stratification of Slavs to south-, east-, and west-Slavic groups, were also found. A phylogeographic analyses of 20 completely sequenced Serbian mitochondrial genomes revealed not only the presence of mtDNA lineages predominantly found within the Slavic gene pool (U4a2a*, U4a2a1, U4a2c, U4a2g, HV10), supporting a common Slavic origin, but also lineages that may have originated within the southern Europe (H5*, H5e1, H5a1v) and the Balkan Peninsula in particular (H6a2b and L2a1k).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajpa.22670DOI Listing
March 2015

The role of Dichaete in transcriptional regulation during Drosophila embryonic development.

BMC Genomics 2013 Dec 8;14:861. Epub 2013 Dec 8.

Department of Genetics, University of Cambridge, Cambridge, UK.

Background: Group B Sox domain transcription factors play conserved roles in the specification and development of the nervous system in higher metazoans. However, we know comparatively little about how these transcription factors regulate gene expression, and the analysis of Sox gene function in vertebrates is confounded by functional compensation between three closely related family members. In Drosophila, only two group B Sox genes, Dichaete and SoxN, have been shown to function during embryonic CNS development, providing a simpler system for understanding the functions of this important class of regulators.

Results: Using a combination of transcriptional profiling and genome-wide binding analysis we conservatively identify over 1000 high confidence direct Dichaete target genes in the Drosophila genome. We show that Dichaete plays key roles in CNS development, regulating aspects of the temporal transcription factor sequence that confer neuroblast identity. Dichaete also shows a complex interaction with Prospero in the pathway controlling the switch from stem cell self-renewal to neural differentiation. Dichaete potentially regulates many more genes in the Drosophila genome and was found to be associated with over 2000 mapped regulatory elements.

Conclusions: Our analysis suggests that Dichaete acts as a transcriptional hub, controlling multiple regulatory pathways during CNS development. These include a set of core CNS expressed genes that are also bound by the related Sox2 gene during mammalian CNS development. Furthermore, we identify Dichaete as one of the transcription factors involved in the neural stem cell transcriptional network, with evidence supporting the view that Dichaete is involved in controlling the temporal series of divisions regulating neuroblast identity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1471-2164-14-861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3866562PMC
December 2013

Characterizing 5-methylcytosine in the mammalian epitranscriptome.

Genome Biol 2013 Nov 29;14(11):215. Epub 2013 Nov 29.

The post-transcriptional modification 5-methylcytosine (m5C) occurs in a wide range of coding and non-coding RNAs. We describe transcriptome-wide approaches to capture the global m5C RNA methylome. We also discuss the potential functions of m5C in RNA and compare them to 6-methyladenosine modifications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/gb4143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4053770PMC
November 2013

metabolicMine: an integrated genomics, genetics and proteomics data warehouse for common metabolic disease research.

Database (Oxford) 2013 9;2013:bat060. Epub 2013 Aug 9.

Cambridge Systems Biology Centre, University of Cambridge, Cambridge CB2 1QR, UK.

Common metabolic and endocrine diseases such as diabetes affect millions of people worldwide and have a major health impact, frequently leading to complications and mortality. In a search for better prevention and treatment, there is ongoing research into the underlying molecular and genetic bases of these complex human diseases, as well as into the links with risk factors such as obesity. Although an increasing number of relevant genomic and proteomic data sets have become available, the quantity and diversity of the data make their efficient exploitation challenging. Here, we present metabolicMine, a data warehouse with a specific focus on the genomics, genetics and proteomics of common metabolic diseases. Developed in collaboration with leading UK metabolic disease groups, metabolicMine integrates data sets from a range of experiments and model organisms alongside tools for exploring them. The current version brings together information covering genes, proteins, orthologues, interactions, gene expression, pathways, ontologies, diseases, genome-wide association studies and single nucleotide polymorphisms. Although the emphasis is on human data, key data sets from mouse and rat are included. These are complemented by interoperation with the RatMine rat genomics database, with a corresponding mouse version under development by the Mouse Genome Informatics (MGI) group. The web interface contains a number of features including keyword search, a library of Search Forms, the QueryBuilder and list analysis tools. This provides researchers with many different ways to analyse, view and flexibly export data. Programming interfaces and automatic code generation in several languages are supported, and many of the features of the web interface are available through web services. The combination of diverse data sets integrated with analysis tools and a powerful query system makes metabolicMine a valuable research resource. The web interface makes it accessible to first-time users, whereas the Application Programming Interface (API) and web services provide convenient data access and tools for bioinformaticians. metabolicMine is freely available online at http://www.metabolicmine.org Database URL: http://www.metabolicmine.org.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/database/bat060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4438919PMC
October 2013

Cooperativity and rapid evolution of cobound transcription factors in closely related mammals.

Cell 2013 Aug;154(3):530-40

Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK.

To mechanistically characterize the microevolutionary processes active in altering transcription factor (TF) binding among closely related mammals, we compared the genome-wide binding of three tissue-specific TFs that control liver gene expression in six rodents. Despite an overall fast turnover of TF binding locations between species, we identified thousands of TF regions of highly constrained TF binding intensity. Although individual mutations in bound sequence motifs can influence TF binding, most binding differences occur in the absence of nearby sequence variations. Instead, combinatorial binding was found to be significant for genetic and evolutionary stability; cobound TFs tend to disappear in concert and were sensitive to genetic knockout of partner TFs. The large, qualitative differences in genomic regions bound between closely related mammals, when contrasted with the smaller, quantitative TF binding differences among Drosophila species, illustrate how genome structure and population genetics together shape regulatory evolution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cell.2013.07.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3732390PMC
August 2013

A new phylogeny for the genus Picea from plastid, mitochondrial, and nuclear sequences.

Mol Phylogenet Evol 2013 Dec 18;69(3):717-27. Epub 2013 Jul 18.

Systematic Botany and Mycology, University of Munich (LMU), Menzinger Strasse 67, 80638 Munich, Germany.

Studies over the past ten years have shown that the crown groups of most conifer genera are only about 15-25 Ma old. The genus Picea (spruces, Pinaceae), with around 35 species, appears to be no exception. In addition, molecular studies of co-existing spruce species have demonstrated frequent introgression. Perhaps not surprisingly therefore previous phylogenetic studies of species relationships in Picea, based mostly on plastid sequences, suffered from poor statistical support. We therefore generated mitochondrial, nuclear, and further plastid DNA sequences from carefully sourced material, striking a balance between alignability with outgroups and phylogenetic signal content. Motif duplications in mitochondrial introns were treated as characters in a stochastic Dollo model; molecular clock models were calibrated with fossils; and ancestral ranges were inferred under maximum likelihood. In agreement with previous findings, Picea diverged from its sister clade 180 million years ago (Ma), and the most recent common ancestor of today's spruces dates to 28 Ma. Different from previous analyses though, we find a large Asian clade, an American clade, and a Eurasian clade. Two expansions occurred from Asia to North America and several between Asia and Europe. Chinese P. brachytyla, American P. engelmannii, and Norway spruce, P. abies, are not monophyletic, and North America has ten, not eight species. Divergence times imply that Pleistocene refugia are unlikely to be the full explanation for the relationships between the European species and their East Asian relatives. Thus, northern Norway spruce may be part of an Asian species complex that diverged from the southern Norway spruce lineage in the Upper Miocene, some 6 Ma, which can explain the deep genetic gap noted in phylogeographic studies of Norway spruce. The large effective population sizes of spruces, and incomplete lineage sorting during speciation, mean that the interspecific relationships within each of the geographic clades require further studies, especially based on genomic information and population genetic data.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ympev.2013.07.004DOI Listing
December 2013

InterMOD: integrated data and tools for the unification of model organism research.

Sci Rep 2013 ;3:1802

Cambridge Systems Biology Centre, University of Cambridge, Cambridge CB2 1QR, United Kingdom.

Model organisms are widely used for understanding basic biology, and have significantly contributed to the study of human disease. In recent years, genomic analysis has provided extensive evidence of widespread conservation of gene sequence and function amongst eukaryotes, allowing insights from model organisms to help decipher gene function in a wider range of species. The InterMOD consortium is developing an infrastructure based around the InterMine data warehouse system to integrate genomic and functional data from a number of key model organisms, leading the way to improved cross-species research. So far including budding yeast, nematode worm, fruit fly, zebrafish, rat and mouse, the project has set up data warehouses, synchronized data models, and created analysis tools and links between data from different species. The project unites a number of major model organism databases, improving both the consistency and accessibility of comparative research, to the benefit of the wider scientific community.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/srep01802DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3647165PMC
February 2014

Identifying targets of the Sox domain protein Dichaete in the Drosophila CNS via targeted expression of dominant negative proteins.

BMC Dev Biol 2013 Jan 5;13. Epub 2013 Jan 5.

Department of Genetics, University of Cambridge, Cambridge, UK.

Background: Group B Sox domain transcription factors play important roles in metazoan central nervous system development. They are, however, difficult to study as mutations often have pleiotropic effects and other Sox family members can mask phenotypes due to functional compensation. In Drosophila melanogaster, the Sox gene Dichaete is dynamically expressed in the embryonic CNS, where it is known to have functional roles in neuroblasts and the ventral midline. In this study, we use inducible dominant negative proteins in combination with ChIP, immunohistochemistry and genome-wide expression profiling to further dissect the role of Dichaete in these two tissues.

Results: We generated two dominant negative Dichaete constructs, one lacking a DNA binding domain and the other fused to the Engrailed transcriptional repressor domain. We expressed these tissue-specifically in the midline and in neuroblasts using the UAS/GAL4 system, validating their use at the phenotypic level and with known target genes. Using ChIP and immunohistochemistry, we identified two new likely direct Dichaete target genes, commisureless in the midline and asense in the neuroectoderm. We performed genome-wide expression profiling in stage 8-9 embryos, identifying almost a thousand potential tissue-specific Dichaete targets, with half of these genes showing evidence of Dichaete binding in vivo. These include a number of genes with known roles in CNS development, including several components of the Notch, Wnt and EGFR signalling pathways.

Conclusions: As well as identifying commisureless as a target, our data indicate that Dichaete helps establish its expression during early midline development but has less effect on its established later expression, highlighting Dichaete action on tissue specific enhancers. An analysis of the broader range of candidate Dichaete targets indicates that Dichaete plays diverse roles in CNS development, with the 500 or so Dichaete-bound putative targets including a number of transcription factors, signalling pathway components and terminal differentiation genes. In the early neurectoderm we implicate Dichaete in the lateral inhibition pathway and show that Dichaete acts to repress the proneural gene asense. Our analysis also reveals that dominant negatives cause off-target effects, highlighting the need to use other experimental data for validating findings from dominant negative studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1471-213X-13-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3541953PMC
January 2013

InterMine: a flexible data warehouse system for the integration and analysis of heterogeneous biological data.

Bioinformatics 2012 Dec 27;28(23):3163-5. Epub 2012 Sep 27.

Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK.

Summary: InterMine is an open-source data warehouse system that facilitates the building of databases with complex data integration requirements and a need for a fast customizable query facility. Using InterMine, large biological databases can be created from a range of heterogeneous data sources, and the extensible data model allows for easy integration of new data types. The analysis tools include a flexible query builder, genomic region search and a library of 'widgets' performing various statistical analyses. The results can be exported in many commonly used formats. InterMine is a fully extensible framework where developers can add new tools and functionality. Additionally, there is a comprehensive set of web services, for which client libraries are provided in five commonly used programming languages.

Availability: Freely available from http://www.intermine.org under the LGPL license.

Contact: g.micklem@gen.cam.ac.uk

Supplementary Information: Supplementary data are available at Bioinformatics online.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/bioinformatics/bts577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3516146PMC
December 2012

A simple and efficient DNA isolation method for Salvia officinalis.

Biochem Genet 2012 Dec 31;50(11-12):881-92. Epub 2012 Jul 31.

Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, P.O. Box 23, 11010, Belgrade, Serbia.

We report an efficient, simple, and cost-effective protocol for the isolation of genomic DNA from an aromatic medicinal plant, common sage (Salvia officinalis L.). Our modification of the standard CTAB protocol includes two polyphenol adsorbents (PVP 10 and activated charcoal), high NaCl concentrations (4 M) for removing polysaccharides, and repeated Sevag treatment to remove proteins and other carbohydrate contaminants. The mean DNA yield obtained with our Protocol 2 was 330.6 μg DNA g(-1) of dry leaf tissue, and the absorbance ratios 260/280 and 260/230 nm averaged 1.909 and 1.894, respectively, revealing lack of contamination. PCR amplifications of one nuclear (26S rDNA) and one chloroplast (rps16-trnK) locus indicated that our DNA isolation protocol may be used in common sage and other aromatic and medicinal plants containing essential oil for molecular biologic and biotechnological studies and for population genetics, phylogeographic, and conservation surveys in which nuclear or chloroplast genomes would be studied in large numbers of individuals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10528-012-9528-yDOI Listing
December 2012

Cost-effectiveness of four immunomodulatory therapies for relapsing-remitting multiple sclerosis: a Markov model based on data a Balkan country in socioeconomic transition.

Vojnosanit Pregl 2009 Jul;66(7):556-62

University of Kragujevac, Medical Faculty, Ul. Svetozara Markovića 69, 34 000 Kragujevac, Serbia.

Background/aim: A cost-effectiveness analyses of immunomodulatory treatments for relapsing-remitting multiple sclerosis (RRMS) in developed countries have shown that any benefit from these drugs is achieved at very high cost. The aim of our study was to compare the cost-effectiveness of five treatment strategies in patients diagnosed with RRMS (symptom management alone and in combination with subcutaneous glatiramer acetate, intramuscular interferon beta-1a, subcutaneous interferon beta-1a, or intramuscular interferon [beta-1b) in a Balkan country in socio-economic transition.

Methods: The Markov model was developed based on the literature about effectiveness and on local Serbian cost calculations. The duration of a cycle in the model was set to a month. The baseline time horizon was 480 months (40 years). The societal perspective was used for costs and outcomes, and they were discounted for 3% annually. Monte Carlo micro simulation with 1000 virtual patients was done.

Results: Significant gain with immunomodulatory therapy was achieved only in relapse-free years, while the time spent in health states EDSS 0.0-5.5 was longer with symptomatic therapy only, and gains in life years and QALYs were only marginal. One QALY gained costs more than a billion of Serbian dinars (more than 20 million US dollars), making each of the four immunomodulatory therapies cost-ineffective.

Conclusion: Our study suggests that immunomodulatory therapy of RRMS in a Balkan country in socioeconomic transition is not cost-effective, regardless of the type of the therapy. Moderate gain in relapse-free years does not translate to gain in QALYs, probably due to adverse effects of immunomodulatory therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2298/vsp0907556jDOI Listing
July 2009

Nonsteroidal antiinflammatory drugs and risk of gastrointestinal bleeding among patients on hemodialysis.

J Nephrol 2009 Jul-Aug;22(4):502-7

Medical Faculty, University of Kragujevac, Kragujevac, Serbia.

Background: Both use of nonsteroidal antiinflammatory drugs (NSAIDs) and chronic renal insufficiency are significant independent risk factors for gastrointestinal bleeding.

Objective: The aim of our study was to investigate whether regular use of NSAIDs further increases the risk of gastrointestinal bleeding among patients with end-stage renal insufficiency on hemodialysis.

Methods: This was a case-control study. Case and control patients were selected from the lists of patients on hemodialysis during the period of 4 months (n=650), at 3 secondary care general hospitals in Serbia. Cases (n=33) were chosen from the study population if they had experienced at least 1 episode of gastrointestinal bleeding during the last 3 years. For each case, at least 1 sex- and age-matched control patient (n=45) was randomly selected from the source population.

Results: Among patients on hemodialysis, NSAIDs users had approximately 3 times higher risk of developing gastrointestinal bleeding, than non-users (crude odds ratio = 3.29; 95% confidence interval [95% CI], 1.28-8.45). After adjustment for potential confounders (sex, age, use of erythropoietin or parenteral iron, frequency of NSAID use, smoking, drinking alcohol, heart failure, arterial hypertension, diabetes mellitus, chronic obstructive pulmonary disease, and use of anticoagulants, antiplatelet agents, beta-blockers, angiotensin-converting enzyme inhibitors or diuretics), the only significant association that remained was between gastrointestinal bleeding and use of NSAIDs (OR adjusted = 5.8; 95% CI, 1.3-26.9; p=0.024).

Conclusion: There is a need for development of effective strategies to prevent gastrointestinal bleeding in patients on hemodialysis who use NSAIDs.
View Article and Find Full Text PDF

Download full-text PDF

Source
September 2009

ChIPing away at the genome: the new frontier travel guide.

Mol Biosyst 2009 Dec;5(12):1421-8

Department of Genetics and Cambridge Systems Biology Centre, University of Cambridge, Downing Street, Cambridge, UK.

Chromatin immunoprecipitation (ChIP) is a powerful technique for obtaining in vivo data on protein-DNA binding, providing an invaluable tool for elucidating gene regulation at a molecular level. Combined with high-throughput methods such as microarrays (ChIP-array) and second generation sequencing (ChIP-seq), the technique is now commonly used for answering questions about protein binding on a genome-wide level. This review focuses on the use of microarrays and sequencing for ChIP studies, provides a critical comparison of the currently used platforms and an overview of the computational methods available, and offers recommendations for optimal use of the techniques in a research context.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/B906179GDOI Listing
December 2009

Biases in Drosophila melanogaster protein trap screens.

BMC Genomics 2009 May 28;10:249. Epub 2009 May 28.

Cambridge Systems Biology Centre, University of Cambridge, Cambridge, UK.

Background: The ability to localise or follow endogenous proteins in real time in vivo is of tremendous utility for cell biology or systems biology studies. Protein trap screens utilise the random genomic insertion of a transposon-borne artificial reporter exon (e.g. encoding the green fluorescent protein, GFP) into an intron of an endogenous gene to generate a fluorescent fusion protein. Despite recent efforts aimed at achieving comprehensive coverage of the genes encoded in the Drosophila genome, the repertoire of genes that yield protein traps is still small.

Results: We analysed the collection of available protein trap lines in Drosophila melanogaster and identified potential biases that are likely to restrict genome coverage in protein trap screens. The protein trap screens investigated here primarily used P-element vectors and thus exhibit some of the same positional biases associated with this transposon that are evident from the comprehensive Drosophila Gene Disruption Project. We further found that protein trap target genes usually exhibit broad and persistent expression during embryonic development, which is likely to facilitate better detection. In addition, we investigated the likely influence of the GFP exon on host protein structure and found that protein trap insertions have a significant bias for exon-exon boundaries that encode disordered protein regions. 38.8% of GFP insertions land in disordered protein regions compared with only 23.4% in the case of non-trapping P-element insertions landing in coding sequence introns (p < 10(-4)). Interestingly, even in cases where protein domains are predicted, protein trap insertions frequently occur in regions encoding surface exposed areas that are likely to be functionally neutral. Considering the various biases observed, we predict that less than one third of intron-containing genes are likely to be amenable to trapping by the existing methods.

Conclusion: Our analyses suggest that the utility of P-element vectors for protein trap screens has largely been exhausted, and that approximately 2,800 genes may still be amenable using piggyBac vectors. Thus protein trap strategies based on current approaches are unlikely to offer true genome-wide coverage. We suggest that either transposons with reduced insertion bias or recombineering-based targeting techniques will be required for comprehensive genome coverage in Drosophila.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1471-2164-10-249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2695487PMC
May 2009

Temperature and flow visualization in a simulation of the Czochralski process using temperature-sensitive liquid crystals.

Ann N Y Acad Sci 2002 Oct;972:158-63

Department of Thermofluid-dynamics and Turbo Machines, University of Applied Sciences of Stralsund, Germany.

There is no doubt today that thermal and thermocapillary convection play a dominant role in momentum, heat, and mass transfer in the Czochralski crystal growth method. Because of the complexity of the problems, measurements in one point of the volume are not sufficient to illuminate the flow topography or to compare the experimental results with real or numerically simulated data. Therefore, it is of great interest to measure the temperatures and velocities in the whole field in order to qualitatively analyze thermally driven convection. The new experimental particle image thermometry method, based on computer-aided color analysis of the TLCs reported here, enables the simultaneous determination of the temperature and velocity fields.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1749-6632.2002.tb04567.xDOI Listing
October 2002