Cause Of Congenital Malformations Research Articles

Rapid genotyping of Toxoplasma gondii isolates via Nanopore-based multi-locus sequencing

Toxoplasma gondii is an obligate intracellular parasite associated with severe disease, especially in the immunosuppressed. It is also a cause of congenital malformation and abortion in both animals and humans and is considered one of the most important foodborne pathogens worldwide with different strains showing variable distribution and differing pathogenicity. Thus, strain-level differentiation of T. gondii isolates is an essential asset in the understanding of parasite’s diversity, geographical distribution, epidemiology and health risk. Here, we designed and implemented an Oxford Nanopore MinION protocol to analyse genomic sequence variation including single nucleotide polymorphisms (SNPs) and insertion/deletion polymorphisms (InDel’s) of four different genomic loci, part of protein coding genes SAG2, SAG3, ROP17 and ROP21. This method provided results with the sequencing depth necessary for accurate differentiation of T. gondii strains and represents a rapid approach compared to conventional techniques which we further validated against environmental samples isolated from wild wood mice. In summary, multi-locus sequence typing (MLST) of both highly conserved and more polymorphic areas of the genome, provided robust data for strain classification in a platform ready for further adaption for other strains and pathogens.

Human Cytomegalovirus Dysregulates Cellular Dual-Specificity Tyrosine Phosphorylation-Regulated Kinases and Sonic Hedgehog Pathway Proteins in Neural Astrocyte and Placental Models.

Human cytomegalovirus (CMV) infection is the leading non-genetic cause of congenital malformation in developed countries, causing significant fetal injury, and in some cases fetal death. The pathogenetic mechanisms through which this host-specific virus infects then damages both the placenta and the fetal brain are currently ill-defined. We investigated the CMV modulation of key signaling pathway proteins for these organs including dual-specificity tyrosine phosphorylation-regulated kinases (DYRK) and Sonic Hedgehog (SHH) pathway proteins using human first trimester placental trophoblast (TEV-1) cells, primary human astrocyte (NHA) brain cells, and CMV-infected human placental tissue. Immunofluorescence demonstrated the accumulation and re-localization of SHH proteins in CMV-infected TEV-1 cells with Gli2, Ulk3, and Shh re-localizing to the CMV cytoplasmic virion assembly complex (VAC). In CMV-infected NHA cells, DYRK1A re-localized to the VAC and DYRK1B re-localized to the CMV nuclear replication compartments, and the SHH proteins re-localized with a similar pattern as was observed in TEV-1 cells. Western blot analysis in CMV-infected TEV-1 cells showed the upregulated expression of Rb, Ulk3, and Shh, but not Gli2. In CMV-infected NHA cells, there was an upregulation of DYRK1A, DYRK1B, Gli2, Rb, Ulk3, and Shh. These in vitro monoculture findings are consistent with patterns of protein upregulation and re-localization observed in naturally infected placental tissue and CMV-infected ex vivo placental explant histocultures. This study reveals CMV-induced changes in proteins critical for fetal development, and identifies new potential targets for CMV therapeutic development.

Seroprevalence of Anti-Cytomegalovirus Antibodies in Pregnant Women from South-West Romania.

Cytomegalovirus (CMV), in addition to other agents, is part of the TORCH complex (Toxoplasma gondii, Rubella virus, Cytomegalovirus, Herpes simplex viruses, and other agents). CMV infection is the most frequent cause of congenital malformations. This study aimed to establish the variation of prevalence of anti-CMV antibodies in pregnant women from the South-West region of Romania, according to demographic factors, such as age and area of residence, in two separate time periods (2013-2016 and 2019-2022). We collected from the hospital records the age, place of residence, and anti-CMV antibody test results using immune electrochemiluminescence and chemiluminescence. This study found that the seroprevalence of anti-CMV IgM antibodies increased slightly from 2013-2016 to 2019-2022, from 1.92% to 2.26%, and for IgG antibodies from 93.68% to 94.96%. In both groups was observed a descending trend of anti-CMV IgM seroprevalence with an increase in age, showing a decrease in seroprevalence from 3.57% to 1.09% in pregnant women from rural areas in the 31-35 years age group, while in urban areas, we observed a decrease in seroprevalence from 11.11% to 3.06% in the <20 years age group. The IgG seroprevalence showed an increase both in rural areas (from 93.97% to 95.52%) and urban areas (from 93.52% to 94.27%). In both groups, seroprevalence was higher in rural areas compared to urban regions. These results show a high rate of immunization against CMV in pregnant women in South-West Romania, which led to a low risk of acquiring the primary infection during pregnancy. However, the increase in the rate of primary CMV infections in pregnancy suggests the need for prioritizing screening programs and improving the existing protocols to enhance maternal and child healthcare.

Vaccine value profile for cytomegalovirus

Cytomegalovirus (CMV) is the most common infectious cause of congenital malformation and a leading cause of developmental disabilities such as sensorineural hearing loss (SNHL), motor and cognitive deficits. The significant disease burden from congenital CMV infection (cCMV) led the US National Institute of Medicine to rank CMV vaccine development as the highest priority. An average of 6.7/1000 live births are affected by cCMV, but the prevalence varies across and within countries. In contrast to other congenital infections such as rubella and toxoplasmosis, the prevalence of cCMV increases with CMV seroprevalence rates in the population. The true global burden of cCMV disease is likely underestimated because most infected infants (85–90 %) have asymptomatic infection and are not identified. However, about 7–11 % of those with asymptomatic infection will develop SNHL throughout early childhood.Although no licensed CMV vaccine exists, several candidate vaccines are in development, including one currently in phase 3 trials. Licensure of one or more vaccine candidates is feasible within the next five years. Various models of CMV vaccine strategies employing different target populations have shown to provide substantial benefit in reducing cCMV. Although CMV can cause end-organ disease with significant morbidity and mortality in immunocompromised individuals, the focus of this vaccine value profile (VVP) is on preventing or reducing the cCMV disease burden.This CMV VVP provides a high-level, comprehensive assessment of the currently available data to inform the potential public health, economic, and societal value of CMV vaccines. The CMV VVP was developed by a working group of subject matter experts from academia, public health groups, policy organizations, and non-profit organizations. All contributors have extensive expertise on various elements of the CMV VVP and have described the state of knowledge and identified the current gaps. The VVP was developed using only existing and publicly available information.

Hallazgos citogenéticos y edad materna en pacientes con Síndrome Down en un hospital de referencia pediátrico en el Perú

Introduction: Down syndrome is a congenital disorder caused by a total or partial trisomy of chromosome 21 and is considered the most common genetic cause of congenital malformations and intellectual disability. The objective of this study was to describe the cytogenetic alterations of patients with Down syndrome and their relationship with maternal age. Methods: Cross-sectional, descriptive-analytical study. 436 patients with Down syndrome admitted to the Instituto Nacional de Salud del Niño during the 2017-2019 period were included. The variables analyzed were: cytogenetic diagnosis and maternal age. Results: It was found that 99,3% (n=433) of patients presented some type of cytogenetic alteration and three patients presented a normal karyotype. The age of the patients at the time of sampling was between 0,03 and 17 years, the male/female ratio was 1.2:1. The most frequent cytogenetic alteration was free trisomy 21 (94,7%), followed by Robertsonian translocation (n=16) and mosaicism (n=6). In the case of maternal age, a median of 37 years was found (range: 13-47). Conclusions: Free trisomy 21 is the most common cytogenetic condition in Down syndrome; however, the Robertsonian translocation and mosaicisms were more frequent in patients whose mothers were les than 35 years old, suggesting that there are other risk factors than advanced maternal age in this group.

The loop-tail mouse model displays open and closed caudal neural tube defects.

Neural tube defects (NTDs) are the second most common cause of congenital malformations and are often studied in animal models. Loop-tail (Lp) mice carry a mutation in the Vangl2 gene, a member of the Wnt-planar cell polarity pathway. In Vangl2+/Lp embryos, the mutation induces a failure in the completion of caudal neural tube closure, but only a small percentage of embryos develop open spina bifida. Here, we show that the majority of Vangl2+/Lp embryos developed caudal closed NTDs and presented cellular aggregates that may facilitate the sealing of these defects. The cellular aggregates expressed neural crest cell markers and, using these as a readout, we describe a systematic method to assess the severity of the neural tube dorsal fusion failure. We observed that this defect worsened in combination with other NTD mutants, Daam1 and Grhl3. Besides, we found that in Vangl2+/Lp embryos, these NTDs were resistant to maternal folic acid and inositol supplementation. Loop-tail mice provide a useful model for research on the molecular interactions involved in the development of open and closed NTDs and for the design of prevention strategies for these diseases.

Malformações congênitas em uma cidade da região metropolitana de Curitiba-PR

Congenital malformations (CM) are structural/functional alterations that occur in the fetus, leading to a socio-economic and emotional impact. This is a retrospective, documentary study with a quantitative approach aiming at identifying the relationship of risk factors and maternal epidemiological profile with the occurrence of CM. It was based on the analysis of 37 medical charts of pregnant women in a municipality in the metropolitan region of Curitiba-PR, between 2019 and 2021. The data revealed a profile: pregnant, multiparous, obese women between 18 and 36 years old, with comorbidities, with no preconception evaluation. The most affected organic systems were the cardiovascular and the nervous systems or multiple systems. An increased risk of fetal malformations was observed in obese women over 25 years old, who used alcohol or tobacco. Although a single cause of CM in that period and place has not been identified, an association was established between maternal epidemiological factors and characteristics of fetal malformations, highlighting the need for preconception health education.

Partial trisomy 9p and partial monosomy 7p of an infant inherited from maternal balanced translocation: a case report

BackgroundSubchromosomal deletions and duplications are the leading cause of congenital malformations and mental retardation in children. With the recent clinical application of genomic microarrays in the evaluation of patients with developmental delays and congenital malformations, it has led to the discovery of several new microdeletion and microduplication syndromes. However, there are no published reports involving patients with both microduplications in the 9p21.1-p24.3 region and microdeletions in the 7p22.1-p22.3 region.Case presentationWe report an infant with an autosomal abnormality confirmed by conventional karyotype combined with copy number variations sequencing (CNV-seq), showing the patient with an unbalanced translocation. The karyotype of the patient was 46, XX, der (7)t (7;9) (p22; p21) and CNV-seq results showed an approximately 32.34-Mb duplication in 9p21.1-p24.3 (200000-32540000) and an approximately 3.3-Mb deletion in 7p22.2-p22.3 (40000-3340000).ConclusionsThe patient carried an unbalanced translocation 46, XX, der (7)t (7;9) (p22; p21) derived from her mother. The clinical presentation is closely related to the size and position of the missing and duplicated chromosomes. To our knowledge, the simultaneous occurrence of de novo partial trisomy 9p(9p21.1-p24.3) and partial monosomy 7p (7p22.2-p22.3) has not previously been reported up until now. The present study additionally demonstrated that CNV-seq combined with karyotype is able to reliably detect unbalanced submicroscopic chromosomal aberrations.

First Trimester Screening Tests Pregnancy and Trisomy 13 Syndrome, Sex Chromosome Aneuploidy in Iran: A Cross-Sectional Study.

Trisomy 13 (T13) and sex chromosome aneuploidies (SCA) are the vital causes of congenital malformations. This study was performed to identify the T13 and SCA with screening tests in the first trimester of pregnancy. In this cross-sectional study, first-trimester combined screening was conducted on 2100 pregnant women referred to Narges Genetics Laboratory, Ahvaz, Iran. Evaluating the first trimester screening tests, including nuchal translucency (NT), crown-rump length (CRL) and pregnancy-associated plasma protein-A (PAPP-A), and free beta of human chorionic gonadotropin (fβhCG) was performed. For a definitive diagnosis of T13 and SCA syndrome, fetal karyotype was evaluated. The average NT and CRL in high-risk group for T13 were 5.96 mm and 61.7 mm respectively and in high-risk groups for SCA were 3.7 mm and 75.9 mm, respectively. Significant correlation was observed among NT, CRL and T13, SCA (P<0.05). The average serum fβhCG and PAAP-A levels in high-risk group for T13 were 0.42 and 0.31, respectively. Significant correlation was observed between decrease fβhCG, PAPP-A and T13 levels and increase fβhCG levels and SCA levels (P<0.05). No Significant correlation was observed between PAPP-A levels and SCA levels (P>0.05). Using special software and karyotype testing, the prenatal screening tests based on the maternal age and gestational age in the first trimester of pregnancy may determine the major risk of fetal chromosomal abnormalities.

First person - Hartmut Cuny.

First Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms, helping researchers promote themselves alongside their papers. Hartmut Cuny is first author on ' Maternal heterozygosity of Slc6a19 causes metabolic perturbation and congenital NAD deficiency disorder in mice', published in DMM. Hartmut is a senior postdoc in the lab of Prof. Sally Dunwoodie at Victor Chang Cardiac Research Institute, Sydney, Australia, investigating the genetic and environmental causes of congenital malformations.

Study of the clinical features of Downs’s syndrome and relation between dermatoglyphics and congenital heart disease if any

Introduction: Down syndrome is one of the most common cause of congenital malformation with mental retardation seen with an estimated prevalence of 1/600 – 1/800 births. A wide range of abnormalities are seen, some of which are characteristic of Downs syndrome. Objectives and Aim: The present study was aimed at studying the various clinical features including dermatologlyphic patterns in Down syndrome and to find any correlation with congenital heart disease. Materials and Methods: 34 children £18 years with features of down syndromes were assessed for various clinical presentation and dermatoglyphic patterns analyzed. Those with congenial heart disease were also noted to check for any correlation with dermatoglyphic patterns in Downs syndrome.3 ml blood was drawn and thyroid function were recorded. Results: The majority of clinical features observed include slanted palpebral fissure, icrocephaly, epicanthal fold, macroglossia, hypotonia, flat facies, brachycephaly, high arched palate. Dermatoglyphic patterns show increased prevalence of simian crease clinodactly ulnal loops on the finger tips and atd angle &gt;45 in the children. Statistically significant correlation was found when clinodactly of the left hand, left third inter digital space pattern, open field defect and sandal gap of the toes was compared with down syndrome children with CHD.

Maternal pregestational diabetes as an factor in the genesis of congenital malformations of the fetus

This review article summarizes the results of modern clinical studies performed domestically or abroad, which provide information on maternal pregestational diabetes (type 1 or 2) shaping a spectrum of congenital malformations of the fetus. Advances in the treatment of diabetes mellitus have reduced the risk of fetal congenital malformations in pregnant women with the disease, but an increase in its incidence among women of childbearing age indicates that this cause of congenital malformations is becoming more relevant every year. This review article presents four diabetes-mediated pathways for the genesis of fetal congenital malformations: those associated with metabolic imbalance or oxidative stress, genetically mediated and caused by insufficient inhibition of apoptosis. Thus, based on clinical studies and meta-analysis over the past ten years, it has been demonstrated that women with pregestational diabetes mellitus are at the highest risk of developing fetal congenital malformations. Achievement of diabetes compensation and physiological nutritional status in such patients determines the favorable course of all stages of pregnancy.

Cytomegalovirus infection in a single-centre Australian neonatal cohort.

Congenital cytomegalovirus (cCMV) is the most common infectious cause of congenital malformation, non-genetic sensorineural hearing loss and neurodevelopmental sequelae in childhood. The primary aim of this retrospective cohort study was to identify the birth and neurodevelopmental outcomes of neonates diagnosed with symptomatic and asymptomatic cCMV in a large regional tertiary referral hospital. This was a retrospective cohort study of laboratory-based cCMV diagnoses in neonates born at a single study centre between January 2005 and January 2020. Audit of medical records was undertaken to evaluate maternal characteristics, symptom patterns, radiological and neurodevelopmental outcomes of neonates meeting the laboratory diagnostic criteria during the first 24 months. There were 45 neonates with proven CMV infection and 27 mothers with proven infection with an associated pregnancy outcome. Nineteen neonates were born at term (>37 weeks). Of these, 32 (71.1%) neonates had a significant intercurrent comorbidity and 22 (48.9%) neonates were reported to have a degree of delay in one or more developmental domains. A large proportion (77.3%) of the symptomatic untreated neonates had an unknown history of maternal infection compared to the asymptomatic (10.0%) and symptomatic treated (53.8%) neonates (P= 0.001). Up to half of the neonates with cCMV were at risk of developing a degree of developmental delay at our centre. Whether these outcomes are related primarily to CMV infection or are confounded by the co-existence of prematurity is unclear and needs further evaluation in prospective studies.

Shape memory engineered scaffold (SMES) for potential repair of neural tube defects

Neural tube defects (NTDs) represent the second most common cause of congenital malformations in the children. Aim of the work is the development of a shape memory engineered scaffold (SMES) focused to potentially improve Myelomeningocele (most common type of spina bifida defect) repair in fetus. Copolymer poly-l-lactide-co-ε-caprolactone (PLA-PCL) 70:30 M ratio, due to its glass transition temperature (Tg°) close to physiologic temperature (32–42 °C) was used to produce electrospun scaffolds that were engineered with MSCs from amniotic fluid. The engineered scaffolds were rolled up and then underwent a cycle of high (T° > Tg°) and low temperature (T° < Tg°) in order to induce solid status change from rubbery to glassy and fix their rolled shape. The scaffolds were characterized for the shape memory parameters Rf% (ability to fix new temperature induced shape) and Rr% (ability to recover the primary shape). Biological characterization included cell viability % determination by MTT test, cytofluorimetry and microscope analysis for DAPI stained and Live-Dead Assay. Scaffold degradation test was performed in amniotic fluid and mechanical properties of electrospun scaffold were evaluated up to 4 months incubation in amniotic fluid simulated in vivo conditions.The preliminary and innovative results obtained from this work permit to consider this SMES a good shape memory material (Rf% =79 ± 5.2; Rr% = 98 ± 3.1) and suitable support for MSCs proliferation.

Preterm Infant of Diabetic Mother with a Retrorectal Mass: A Troubling Tail Tale.

Preterm Infant of Diabetic Mother with a Retrorectal Mass: A Troubling Tail Tale.

Parents' perceived knowledge and beliefs on congenital malformations and their causes in the Amhara region, Ethiopia. A qualitative study.

IntroductionKnowledge and beliefs of people on congenital malformations and their causes differ from society to society. As a result, there is a paucity of understanding community perceived knowledge and beliefs towards congenital malformations and their risk factors among children’s parents. Therefore, I sought to identify perceived knowledge and beliefs of parents on congenital malformations and their causes.MethodsAn in-depth discussion and interview were carried out on purposively selected forty participants (women and men) in the Amhara region, Ethiopia. The data were collected from June to July, 2015. Semi-structured guiding topics/questions were used during the discussions and in-depth interviews. Note and audio records were taken while the participants discussed the topics. After the discussions and in-depth interviews were completed, the transcripts were read repeatedly to understand the participant’s words, phrases, ideas, and concepts. Then notes were taken to combine pieces of similar transcripts. I have employed thematic framework analysis. The relevant transcripts were scrutinized, labeled and coded manually based on their relevance to the objective of the study. Then the coded transcripts were determined and categorized according to the type of thematic variables.ResultsThe participants responded on three aspects of lived experience, perceived knowledge and beliefs on congenital malformations and their causes. Nearly half of the participants’ beliefs on the causes of congenital malformations were related to sin, contraceptive pills, un-prescribed drugs/medication use, and fertilizers (that is eating crops grown by using fertilizers). Almost all said that raising a child with a major congenital malformation was very difficult. About half of the participants’ belief on congenital malformations were traditional and resulted from poor awareness.ConclusionThe findings of the present study highlight the challenges and impacts of congenital malformations on parents who had children with and without congenital malformation. Lived experience, perceived knowledge and beliefs of children parents on congenital malformation and their causes can be helpful information for designing preventive actions. Hence, planning a preventive strategy and providing health education on congenital malformations and their causes for children parents are very necessary.

Overview of the Impacts of Pesticides on Human Health in Municipalities with high use and consumption in SPst - Brazil

BACKGROUND AND AIM: The research and activities developed by the São Paulo Forum to Combat Impacts on Pesticides and Transgenics, involve municipalities with higher levels of aerial spraying and where the mortality rate is different. The Forum is composed of members of civil society and public institutions. OBJECTIVE in this symposium: To analyze intoxications, congenital malfomation and the profile of cancer mortality in municipalities where high levels of pesticides were found in water for human consumption. METHODS: Descriptive cross-sectional study based on data from the Ministry of Health/DATASUS on deaths and poisoning by pesticides, domestic use, use in public health and rodenticides in municipalities in the State of São Paulo. RESULTS:Between 2010 and 2019, 113,245 intoxications were reported in Brazil, 60,025 of which were attempted suicides and 39,255 of accidental and habitual use. Of the intoxications in Brazil, 78% were unrelated to work and 3,513 evolved to deaths.In SP state congenital malformations are the third leading cause of child and adolescent deaths (2.41 deaths/1000 inhab) and neoplasms, the fifth leading cause (1.92 deaths/1,000 inhabitants). In 11 municipalities where there is aerial spraying, the rate of neoplasms is 3.49 /100 thousand inhabitants and the second cause of congenital malformation in 5 of these municipalities. The 113,245 cases of poisoning in Brazil, 74.6% of the victims lived in urban areas. In relation to the São Paulo st, 86% lived in urban. Regarding color/race, in Brazil 43.1% were black. Most are between 20 and 39 yo and 26.8% were children under 1 year and 19 yo. CONCLUSIONS:When analyzing the data on the commercialization of pesticides in Brazil, comparing with the incidences of notification of poisoning by pesticides (for agricultural, domestic, public health and rodenticide), a proportional growth is observed, as each product is consumed.We conclude that information is fundamental for society to seek public policies. KEYWORDS: Pesticides,Occupational exposures,Mortality,Toxicology,Water quality

Inherited unbalanced translocation (4p16.3p15.32 duplication/8p23.3p23.2deletion) in the four generation pedigree with intellectual disability/developmental delay

Chromosomal copy number variants (CNVs) are an important cause of congenital malformations and mental retardation. This study reported a large Chinese pedigree (4-generation, 76 members) with mental retardation caused by chromosome microduplication/microdeletion. There were 10 affected individuals with intellectual disability (ID), developmental delay (DD), and language delay phenotypes. SNP array analysis was performed in the proband and eight patients and found all of them had a microduplication of chromosome 4p16.3p15.2 and a microdeletion of chromosome 8p23.3p23.2. The high-resolution karyotyping analysis of the proband had unbalanced karyotype [46, XY, der(8)t(4;8)(p15.2;p23.1)mat], his mother had balanced karyotype [46, XX, t(4;8) (p15.2;p23.1)], whereas his father had normal karyotype [46,XY]. Fluorescence in situ hybridization (FISH) analysis further confirmed that the proband’s mother had a balanced translocation between the short arm terminal segment of chromosome 4 and the short arm end segment of chromosome 8, ish t(4;8)(8p + ,4q + ;4p + ,8q +). In conclusion, all the patients inherited chromosomes 8 with 4p16.3p15.2 duplication and 8p23.3p23.2 deletion from their parental balanced translocation, which might be the cause of the prevalence of intellectual disability. Meanwhile, 8p23.3p23.2 deletion, rather than 4p16.3p15.2 duplication might cause a more severe clinical syndrome.

Non-human Primate Models to Investigate Mechanisms of Infection-Associated Fetal and Pediatric Injury, Teratogenesis and Stillbirth.

A wide array of pathogens has the potential to injure the fetus and induce teratogenesis, the process by which mutations in fetal somatic cells lead to congenital malformations. Rubella virus was the first infectious disease to be linked to congenital malformations due to an infection in pregnancy, which can include congenital cataracts, microcephaly, hearing impairment and congenital heart disease. Currently, human cytomegalovirus (HCMV) is the leading infectious cause of congenital malformations globally, affecting 1 in every 200 infants. However, our knowledge of teratogenic viruses and pathogens is far from complete. New emerging infectious diseases may induce teratogenesis, similar to Zika virus (ZIKV) that caused a global pandemic in 2016–2017; thousands of neonates were born with congenital microcephaly due to ZIKV exposure in utero, which also included a spectrum of injuries to the brain, eyes and spinal cord. In addition to congenital anomalies, permanent injury to fetal and neonatal organs, preterm birth, stillbirth and spontaneous abortion are known consequences of a broader group of infectious diseases including group B streptococcus (GBS), Listeria monocytogenes, Influenza A virus (IAV), and Human Immunodeficiency Virus (HIV). Animal models are crucial for determining the mechanism of how these various infectious diseases induce teratogenesis or organ injury, as well as testing novel therapeutics for fetal or neonatal protection. Other mammalian models differ in many respects from human pregnancy including placentation, labor physiology, reproductive tract anatomy, timeline of fetal development and reproductive toxicology. In contrast, non-human primates (NHP) most closely resemble human pregnancy and exhibit key similarities that make them ideal for research to discover the mechanisms of injury and for testing vaccines and therapeutics to prevent teratogenesis, fetal and neonatal injury and adverse pregnancy outcomes (e.g., stillbirth or spontaneous abortion). In this review, we emphasize key contributions of the NHP model pre-clinical research for ZIKV, HCMV, HIV, IAV, L. monocytogenes, Ureaplasma species, and GBS. This work represents the foundation for development and testing of preventative and therapeutic strategies to inhibit infectious injury of human fetuses and neonates.

Symmetry and fluctuation of cell movements in neural crest-derived facial mesenchyme.

ABSTRACTIn the face, symmetry is established when bilateral streams of neural crest cells leave the neural tube at the same time, follow identical migration routes and then give rise to the facial prominences. However, developmental instability exists, particularly surrounding the steps of lip fusion. The causes of instability are unknown but inability to cope with developmental fluctuations are a likely cause of congenital malformations, such as non-syndromic orofacial clefts. Here, we tracked cell movements over time in the frontonasal mass, which forms the facial midline and participates in lip fusion, using live-cell imaging of chick embryos. Our mathematical examination of cell velocity vectors uncovered temporal fluctuations in several parameters, including order/disorder, symmetry/asymmetry and divergence/convergence. We found that treatment with a Rho GTPase inhibitor completely disrupted the temporal fluctuations in all measures and blocked morphogenesis. Thus, we discovered that genetic control of symmetry extends to mesenchymal cell movements and that these movements are of the type that could be perturbed in asymmetrical malformations, such as non-syndromic cleft lip.This article has an associated ‘The people behind the papers’ interview.