17 research outputs found
Idiosyncratic MĂČjiÄng virus attachment glycoprotein directs a host-cell entry pathway distinct from genetically related henipaviruses
In 2012, cases of lethal pneumonia among Chinese miners prompted the isolation of a rat-borne henipavirus (HNV), MĂČjiÄng virus (MojV). Although MojV is genetically related to highly pathogenic bat-borne henipaviruses, the absence of a conserved ephrin receptor-binding motif in the MojV attachment glycoprotein (MojV-G) indicates a differing host-cell recognition mechanism. Here we find that MojV-G displays a six-bladed ÎČ-propeller fold bearing limited similarity to known paramyxoviral attachment glycoproteins, in particular at host receptor-binding surfaces. We confirm the inability of MojV-G to interact with known paramyxoviral receptors in vitro, indicating an independence from well-characterized ephrinB2/B3, sialic acid and CD150-mediated entry pathways. Furthermore, we find that MojV-G is antigenically distinct, indicating that MojV would less likely be detected in existing large-scale serological screening studies focused on well-established HNVs. Altogether, these data indicate a unique host-cell entry pathway for this emerging and potentially pathogenic HNV
Clear cell carcinoma of ovary and uterus
Clear cell carcinomas of the female genital tract are rare tumours with a fearsome reputation for having poor responses to conventional platinum-based chemotherapy and poor prognosis. However, it is now clear that early-stage ovarian clear cell carcinoma has an excellent prognosis and may not require any adjuvant therapy. In addition, radiotherapy may also have a key role to play in adjuvant management of clear cell tumours. Identification of patients who truly do not need adjuvant chemotherapy is important. The past 3Â years has seen a significant improvement in our understanding of clear cell carcinoma biologyâin particular, the role of mutations in the chromatin remodelling gene ARID1A as key drivers that are common to clear cell carcinomas of ovarian and endometrial origin. Moreover, gynaecological clear cell carcinomas appear to share many features with renal clear cell tumours, suggesting a common pathogenesis. This raises the possibility of clinical trials that include patients with clear cell tumours from different organs of origin. Dissecting the role of disordered chromatin organisation in clear cell carcinoma pathogenesis is a key priority. Finally, the role of endometriosis and the attendant chronic inflammation are recognised. The inflammatory cytokine interleukin-6 appears to play a key role in clear cell carcinoma biology and is an excellent potential therapeutic target
Alkane Functionalization via Electrophilic Activation
Electrophilic activation, which may be defined as the substitution of a
transition metal center for a proton to generate a new metalâcarbon bond, is the
basis of a number of promising approaches to selective catalytic functionalization
of alkanes. The field was introduced by the groundbreaking chemistry exhibited by
aqueous chloroplatinum complexes, reported by Shilov in the early 1970s. Since
then the field has expanded greatly, and electrophilic alkane activation has been
demonstrated using a wide variety of species. These include ligand-supported
platinum complexes; complexes of additional late transition metals, most commonly
palladium but also iridium, gold and others; and even post-transition metals
such as mercury. That body of work is surveyed here, with particular emphasis on
mechanistic understanding, examples of actual functionalization at sp^3-hybridized
CâH bonds in alkanes and related compounds, and assessment of the further
development that will be needed for practical applications