22 research outputs found
Glycomics Analysis of Mammalian Heparan Sulfates Modified by the Human Extracellular Sulfatase HSulf2
The Sulfs are a family of endosulfatases that selectively modify the 6O-sulfation state of cell-surface heparan sulfate (HS) molecules. Sulfs serve as modulators of cell-signaling events because the changes they induce alter the cell surface co-receptor functions of HS chains. A variety of studies have been aimed at understanding how Sulfs modify HS structure, and many of these studies utilize Sulf knockout cell lines as the source for the HS used in the experiments. However, genetic manipulation of Sulfs has been shown to alter the expression levels of HS biosynthetic enzymes, and in these cases an assessment of the fine structural changes induced solely by Sulf enzymatic activity is not possible. Therefore, the present work aims to extend the understanding of substrate specificities of HSulf2 using in vitro experiments to compare HSulf2 activities on HS from different organ tissues.To further the understanding of Sulf enzymatic activity, we conducted in vitro experiments where a variety of mammalian HS substrates were modified by recombinant human Sulf2 (HSulf2). Subsequent to treatment with HSulf2, the HS samples were exhaustively depolymerized and analyzed using size-exclusion liquid chromatography-mass spectrometry (SEC-LC/MS). We found that HSulf2 activity was highly dependent on the structural features of the HS substrate. Additionally, we characterized, for the first time, the activity of HSulf2 on the non-reducing end (NRE) of HS chains. The results indicate that the action pattern of HSulf2 at the NRE is different compared to internally within the HS chain.The results of the present study indicate that the activity of Sulfs is dependent on the unique structural features of the HS populations that they edit. The activity of HSulf2 at HS NREs implicates the Sulfs as key regulators of this region of the chains, and concomitantly, the protein-binding events that occur there
Leadership, action, learning and accountability to deliver quality care for women, newborns and children
Recognizing the need for action, the
national governments of Bangladesh,
Côte d’Ivoire, Ethiopia, Ghana, India,
Malawi, Nigeria, Uganda and United Republic
of Tanzania, together with WHO,
the United Nations Children’s Fund
(UNICEF), the United Nations Population
Fund (UNFPA), implementation
partners and other stakeholders, have
established the Network for Improving
Quality of Care for Maternal Newborn
and Child Health care.10 The network has
agreed to pursue the ambitious goals of
halving maternal and newborn deaths
and stillbirths and improving experience
of care in participating health facilities
within five years of implementation.
Under the leadership of the participating
countries’ health ministries, the
network will support the implementation
of national frameworks for quality
improvement by pursuing four strategic
objectives: (i) leadership by building and
strengthening national institutions and
processes for improving quality of care;
(ii) action by accelerating and sustaining
implementation of quality-of-care
improvement packages through operationalizing
a standards-based approach
to quality improvement; (iii) learning by
promoting joint learning and generating
evidence on quality planning, improvement
and control of health services;
and (iv) accountability by developing,
strengthening and sustaining institutions
and mechanisms for accountability
of quality maternal, neonatal and child
health services that are equitable and
dignified