19 research outputs found
Global report on preterm birth and stillbirth (2 of 7): discovery science
<p>Abstract</p> <p>Background</p> <p>Normal and abnormal processes of pregnancy and childbirth are poorly understood. This second article in a global report explains what is known about the etiologies of preterm births and stillbirths and identifies critical gaps in knowledge. Two important concepts emerge: the continuum of pregnancy, beginning at implantation and ending with uterine involution following birth; and the multifactorial etiologies of preterm birth and stillbirth. Improved tools and data will enable discovery scientists to identify causal pathways and cost-effective interventions.</p> <p>Pregnancy and parturition continuum</p> <p>The biological process of pregnancy and childbirth begins with implantation and, after birth, ends with the return of the uterus to its previous state. The majority of pregnancy is characterized by rapid uterine and fetal growth without contractions. Yet most research has addressed only uterine stimulation (labor) that accounts for <0.5% of pregnancy.</p> <p>Etiologies</p> <p>The etiologies of preterm birth and stillbirth differ by gestational age, genetics, and environmental factors. Approximately 30% of all preterm births are indicated for either maternal or fetal complications, such as maternal illness or fetal growth restriction. Commonly recognized pathways leading to preterm birth occur most often during the gestational ages indicated: (1) inflammation caused by infection (22-32 weeks); (2) decidual hemorrhage caused by uteroplacental thrombosis (early or late preterm birth); (3) stress (32-36 weeks); and (4) uterine overdistention, often caused by multiple fetuses (32-36 weeks). Other contributors include cervical insufficiency, smoking, and systemic infections. Many stillbirths have similar causes and mechanisms. About two-thirds of late fetal deaths occur during the antepartum period; the other third occur during childbirth. Intrapartum asphyxia is a leading cause of stillbirths in low- and middle-income countries.</p> <p>Recommendations</p> <p>Utilizing new systems biology tools, opportunities now exist for researchers to investigate various pathways important to normal and abnormal pregnancies. Improved access to quality data and biological specimens are critical to advancing discovery science. Phenotypes, standardized definitions, and uniform criteria for assessing preterm birth and stillbirth outcomes are other immediate research needs.</p> <p>Conclusion</p> <p>Preterm birth and stillbirth have multifactorial etiologies. More resources must be directed toward accelerating our understanding of these complex processes, and identifying upstream and cost-effective solutions that will improve these pregnancy outcomes.</p
Genetic and antigenic variation of the bovine tick-borne pathogen Theileria parva in the Great Lakes region of Central Africa
BACKGROUND : Theileria parva causes East Coast fever (ECF), one of the most economically important tick-borne diseases
of cattle in sub-Saharan Africa. A live immunisation approach using the infection and treatment method (ITM)
provides a strong long-term strain-restricted immunity. However, it typically induces a tick-transmissible carrier state
in cattle and may lead to spread of antigenically distinct parasites. Thus, understanding the genetic composition of T.
parva is needed prior to the use of the ITM vaccine in new areas. This study examined the sequence diversity and the
evolutionary and biogeographical dynamics of T. parva within the African Great Lakes region to better understand the
epidemiology of ECF and to assure vaccine safety. Genetic analyses were performed using sequences of two antigencoding
genes, Tp1 and Tp2, generated among 119 T. parva samples collected from cattle in four agro-ecological zones
of DRC and Burundi.
RESULTS : The results provided evidence of nucleotide and amino acid polymorphisms in both antigens, resulting
in 11 and 10 distinct nucleotide alleles, that predicted 6 and 9 protein variants in Tp1 and Tp2, respectively. Theileria
parva samples showed high variation within populations and a moderate biogeographical sub-structuring due to the
widespread major genotypes. The diversity was greater in samples from lowlands and midlands areas compared to
those from highlands and other African countries. The evolutionary dynamics modelling revealed a signal of selective
evolution which was not preferentially detected within the epitope-coding regions, suggesting that the observed
polymorphism could be more related to gene flow rather than recent host immune-based selection. Most alleles
isolated in the Great Lakes region were closely related to the components of the trivalent Muguga vaccine.
CONCLUSIONS : Our findings suggest that the extensive sequence diversity of T. parva and its biogeographical distribution
mainly depend on host migration and agro-ecological conditions driving tick population dynamics. Such
patterns are likely to contribute to the epidemic and unstable endemic situations of ECF in the region. However, the fact that ubiquitous alleles are genetically similar to the components of the Muguga vaccine together with the limited
geographical clustering may justify testing the existing trivalent vaccine for cross-immunity in the region.Additional file 1: Table S1. Cattle blood sample distribution across agroecological
zones.Additional file 2: Table S2. Nucleotide and amino acid sequences of Tp1
and Tp2 antigen epitopes from T. parva Muguga reference sequence.Additional file 3: Table S3. Characteristics of 119 T. parva samples
obtained from cattle in different agro-ecological zones (AEZs) of The
Democratic Republic of Congo and Burundi.Additional file 4: Figure S1. Multiple sequence alignment of the 11 Tp1
gene alleles obtained in this study.Additional file 5: Table S4. Estimates of evolutionary divergence
between gene alleles for Tp1 and Tp2, using proportion nucleotide
distance.Additional file 6: Table S5. Tp1 and Tp2 genes alleles with their corresponding
antigen variants.Additional file 7: Table S6. Amino acid variants of Tp1 and Tp2 CD8+
T
cell target epitopes of T. parva from DRC and Burundi.Additional file 8: Figure S2. Multiple sequence alignment of the 10 Tp2
gene alleles obtained in this study.Additional file 9: Table S7. Distribution of Tp1 gene alleles of T. parva
from cattle and buffalo in the sub-Saharan region of Africa.Additional file 10: Table S8. Distribution of Tp2 gene alleles of T. parva
from cattle and buffalo in the sub-Saharan region of Africa.Additional file 11: Figure S3. Neighbor-joining tree showing phylogenetic
relationships among 48 Tp1 gene alleles described in Africa.Additional file 12: Figure S4. Phylogenetic tree showing the relationships
among concatenated Tp1 and Tp2 nucleotide sequences of 93 T.
parva samples from cattle in DRC and Burundi.This study is part of the PhD work supported by the University of Namur (UNamur,
Belgium) through the UNamur-CERUNA institutional PhD grant awarded
to GSA for bioinformatic analyses, interpretation of data and manuscript write
up in Belgium. The laboratory aspects (molecular biology analysis) of the
project were supported by the BecA-ILRI Hub through the Africa Biosciences
Challenge Fund (ABCF) programme. The ABCF Programme is funded by
the Australian Department for Foreign Affairs and Trade (DFAT) through the
BecA-CSIRO partnership; the Syngenta Foundation for Sustainable Agriculture
(SFSA); the Bill & Melinda Gates Foundation (BMGF); the UK Department for International Development (DFID); and the Swedish International Development
Cooperation Agency (Sida). The ABCF Fellowship awarded to GAS was
funded by BMGF grant (OPP1075938). Sample collection, field equipment and
preliminary sample processing were supported through the “Theileria” project
co-funded to the Université Evangélique en Afrique (UEA) by the Agence
Universitaire de la Francophonie (AUF) and the Communauté Economique
des Pays des Grands Lacs (CEPGL). The International Foundation for Science
(IFS, Stockholm, Sweden) supported the individual scholarship awarded to
GSA (grant no. IFS-92890CA3) for field work and part of field equipment to the
“Theileria” project.http://www.parasitesandvectors.comam2020Veterinary Tropical Disease
The genomes of three stocks comprising the most widely utilized live sporozoite Theileria parva vaccine exhibit very different degrees and patterns of sequence divergence
RNA processing and multiple transcription initiation sites result in transcript size heterogeneity in maize mitochondria
Wheat mitochondrial 26S ribosomal RNA gene has no intron and is present in multiple copies arising by recombination
The 18S and 5S ribosomal RNA genes in Oenothera mitochondria: Sequence rearrangments in the 18S and 5S rRNA genes of higher plants
Cross hybridization between organelle RNAs and mitochondrial and chloroplast genomes in Brassica
Homology in the region containing a tRNATrp gene and a (complete or partial) tRNAPro gene in wheat mitochondrial and chloroplast genomes
Characterization of the potato mitochondrial transcription unit containing 'native' trnS (GCU), trnF (GAA) and trnP (UGG)
In order to identify the sequences promoting the expression of plant mitochondrial tRNA genes, we have characterized the trnS (GCU), trnF (GAA) and trnP (UGG) transcription unit of the potato mitochondrial genome. These three tRNA genes were shown to be co-transcribed as a 1800 nt long primary transcript. The transcription initiation site located 305 to 312 nt upstream of trnS is surrounded by a purine-rich region but does not contain the consensus motif proposed as a promoter element in dicotyledonous plants. Differential labelling of potato mitochondrial RNA with either guanylyltransferase or T4 polynucleotide kinase suggests that this site corresponds to the unique functional region responsible for the transcription of these three tRNA genes. The initiation site recently found upstream of Oenothera mitochondrial rr trnF does not seem to be used in potato mitochondria, although a very similar sequence is present 317 nt upstream of the corresponding potato gene. Major processing sites were identified at the 3' end of each tRNA gene. Another processing site, surrounded by a double hairpin structure, is located 498 nt downstream of trnP in stretch of 10 A residues. As judged from northern experiments, this region is close to the determination site of this transcription unit