Hoxa13 regulates expression of common Hox target genes involved in cartilage development to coordinate the expansion of the autopodal anlage

To elucidate the role of Hox genes in limb cartilage development, we identified the target genes of HOXA11 and HOXA13 by ChIP‐Seq. The ChIP DNA fragment contained evolutionarily conserved sequences and multiple highly conserved HOX binding sites. A substantial portion of the HOXA11 ChIP fragment overlapped with the HOXA13 ChIP fragment indicating that both factors share common targets. Deletion of the target regions neighboring Bmp2 or Tshz2 reduced their expression in the autopod suggesting that they function as the limb bud‐specific enhancers. We identified the Hox downstream genes as exhibiting expression changes in the Hoxa13 knock out (KO) and Hoxd11‐13 deletion double mutant (Hox13 dKO) autopod by Genechip analysis. The Hox downstream genes neighboring the ChIP fragment were defined as the direct targets of Hox. We analyzed the spatial expression pattern of the Hox target genes that encode two different categories of transcription factors during autopod development and Hox13dKO limb bud. (a) Bcl11a, encoding a repressor of cartilage differentiation, was expressed in the E11.5 autopod and was substantially reduced in the Hox13dKO. (b) The transcription factors Aff3, Bnc2, Nfib and Runx1t1 were expressed in the zeugopodal cartilage but not in the autopod due to the repressive or relatively weak transcriptional activity of Hox13 at E11.5. Interestingly, the expression of these genes was later observed in the autopodal cartilage at E12.5. These results indicate that Hox13 transiently suspends the cartilage differentiation in the autopodal anlage via multiple pathways until establishing the paddle‐shaped structure required to generate five digits

Zika virus infection in pregnancy: a systematic review of disease course and complications

OBJECTIVES: To characterize maternal Zika virus (ZIKV) infection and complement the evidence base for the WHO interim guidance on pregnancy management in the context of ZIKV infection. METHODS: We searched the relevant database from inception until March 2016. Two review authors independently screened and assessed full texts of eligible reports and extracted data from relevant studies. The quality of studies was assessed using the Newcastle-Ottawa Scale (NOS) and the National Institute of Health (NIH) tool for observational studies and case series/reports, respectively. RESULTS: Among 142 eligible full-text articles, 18 met the inclusion criteria (13 case series/reports and five cohort studies). Common symptoms among pregnant women with suspected/confirmed ZIKV infection were fever, rash, and arthralgia. One case of Guillain-Barre syndrome was reported among ZIKV-infected mothers, no other case of severe maternal morbidity or mortality reported. Complications reported in association with maternal ZIKV infection included a broad range of fetal and newborn neurological and ocular abnormalities; fetal growth restriction, stillbirth, and perinatal death. Microcephaly was the primary neurological complication reported in eight studies, with an incidence of about 1% among newborns of ZIKV infected women in one study. CONCLUSION: Given the extensive and variable fetal and newborn presentations/complications associated with prenatal ZIKV infection, and the dearth of information provided, knowledge gaps are evident. Further research and comprehensive reporting may provide a better understanding of ZIKV infection in pregnancy and attendant maternal/fetal complications. This knowledge could inform the creation of effective and evidence-based strategies, guidelines and recommendations aimed at the management of maternal ZIKV infection. Adherence to current best practice guidelines for prenatal care among health providers is encouraged, in the context of maternal ZIKV infection

Zika virus infection in pregnancy: a systematic review of disease course and complications

OBJECTIVES: To characterize maternal Zika virus (ZIKV) infection and complement the evidence base for the WHO interim guidance on pregnancy management in the context of ZIKV infection. METHODS: We searched the relevant database from inception until March 2016. Two review authors independently screened and assessed full texts of eligible reports and extracted data from relevant studies. The quality of studies was assessed using the Newcastle-Ottawa Scale (NOS) and the National Institute of Health (NIH) tool for observational studies and case series/reports, respectively. RESULTS: Among 142 eligible full-text articles, 18 met the inclusion criteria (13 case series/reports and five cohort studies). Common symptoms among pregnant women with suspected/confirmed ZIKV infection were fever, rash, and arthralgia. One case of Guillain-Barre syndrome was reported among ZIKV-infected mothers, no other case of severe maternal morbidity or mortality reported. Complications reported in association with maternal ZIKV infection included a broad range of fetal and newborn neurological and ocular abnormalities; fetal growth restriction, stillbirth, and perinatal death. Microcephaly was the primary neurological complication reported in eight studies, with an incidence of about 1% among newborns of ZIKV infected women in one study. CONCLUSION: Given the extensive and variable fetal and newborn presentations/complications associated with prenatal ZIKV infection, and the dearth of information provided, knowledge gaps are evident. Further research and comprehensive reporting may provide a better understanding of ZIKV infection in pregnancy and attendant maternal/fetal complications. This knowledge could inform the creation of effective and evidence-based strategies, guidelines and recommendations aimed at the management of maternal ZIKV infection. Adherence to current best practice guidelines for prenatal care among health providers is encouraged, in the context of maternal ZIKV infection

Podocytes use FcRn to clear IgG from the glomerular basement membrane

The glomerular filtration barrier prevents large serum proteins from being lost into the urine. It is not known, however, why the filter does not routinely clog with large proteins that enter the glomerular basement membrane (GBM). Here, we provide evidence that an active transport mechanism exists to remove immunoglobulins that accumulate at the filtration barrier. We found that FcRn, an IgG and albumin transport receptor, is expressed in podocytes and functions to internalize IgG from the GBM. Mice lacking FcRn accumulated IgG in the GBM as they aged, and tracer studies showed delayed clearance of IgG from the kidneys of FcRn-deficient mice. Supporting a role for this pathway in disease, saturating the clearance mechanism potentiated the pathogenicity of nephrotoxic sera. These studies support the idea that podocytes play an active role in removing proteins from the GBM and suggest that genetic or acquired impairment of the clearance machinery is likely to be a common mechanism promoting glomerular diseases

Additional file 1: of Zika virus infection in pregnancy: a systematic review of disease course and complications

Database search strategies for prenatal diagnosis of microcephaly in the context of ZIKV infection on March 3rd 2016. (DOCX 29 kb