12 research outputs found
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
Health Facility Staff Training for Improving Breastfeeding Outcome: A Systematic Review for Step 2 of the Baby-Friendly Hospital Initiative
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