Showing papers by "Ajay Kumar Mishra published in 2017"
TL;DR: It is proposed that defective intercellular adhesion contributes to uncontrolled cSCC growth by preventing inhibition of YAP/WBP2, and YAP and WPB2 are upregulated in actively proliferating cells of mouse and human epidermis and cS CC, and downregulated during terminal differentiation.
Abstract: Individual human epidermal cells differ in their self-renewal ability. To uncover the molecular basis for this heterogeneity, we performed genome-wide pooled RNA interference screens and identified genes conferring a clonal growth advantage on normal and neoplastic (cutaneous squamous cell carcinoma, cSCC) human epidermal cells. The Hippo effector YAP was amongst the top positive growth regulators in both screens. By integrating the Hippo network interactome with our data sets, we identify WW-binding protein 2 (WBP2) as an important co-factor of YAP that enhances YAP/TEAD-mediated gene transcription. YAP and WPB2 are upregulated in actively proliferating cells of mouse and human epidermis and cSCC, and downregulated during terminal differentiation. WBP2 deletion in mouse skin results in reduced proliferation in neonatal and wounded adult epidermis. In reconstituted epidermis YAP/WBP2 activity is controlled by intercellular adhesion rather than canonical Hippo signalling. We propose that defective intercellular adhesion contributes to uncontrolled cSCC growth by preventing inhibition of YAP/WBP2.
79 citations
TL;DR: It is concluded that an auto-regulatory phosphatase network maintains epidermal homeostasis by controlling the onset and duration of commitment.
Abstract: Epidermal homeostasis depends on a balance between stem cell renewal and terminal differentiation. The transition between the two cell states, termed commitment, is poorly understood. Here, we characterise commitment by integrating transcriptomic and proteomic data from disaggregated primary human keratinocytes held in suspension to induce differentiation. Cell detachment induces several protein phosphatases, five of which - DUSP6, PPTC7, PTPN1, PTPN13 and PPP3CA - promote differentiation by negatively regulating ERK MAPK and positively regulating AP1 transcription factors. Conversely, DUSP10 expression antagonises commitment. The phosphatases form a dynamic network of transient positive and negative interactions that change over time, with DUSP6 predominating at commitment. Boolean network modelling identifies a mandatory switch between two stable states (stem and differentiated) via an unstable (committed) state. Phosphatase expression is also spatially regulated in vivo and in vitro. We conclude that an auto-regulatory phosphatase network maintains epidermal homeostasis by controlling the onset and duration of commitment.
52 citations
TL;DR: The synthesis of two new stoichiometric compounds, namely KBr3 and KBr5, at high pressures in the K-Br system are reported, until now, KBr was the only known compound in this system.
Abstract: Recently, the search for and synthesis of unconventional stoichiometric compounds have become one of the most active areas of high pressure research. Here, we report the synthesis of two new stoichiometric compounds, namely KBr3 and KBr5, at high pressures in the K–Br system. Until now, KBr was the only known compound in this system. Two independent experimental techniques, namely Raman spectroscopy and X-ray diffraction measurements, were employed to detect and confirm the formation of the new compounds. A room temperature chemical reaction between KBr and Br2 resulted in the formation of orthorhombic KBr3 at ∼2.0 GPa. Further compression led to the formation of monoclinic KBr5 at ∼6.0 GPa. This was accompanied by an anomalously large pressure (>2 GPa) increase inside the sample chamber and it remained stable up to the highest pressure, 24 GPa, of our study. Upon decompression, KBr5 remained stable down to 5.0 GPa. High-pressure (14–20 GPa) and high-temperature (>1500 K) laser heating experiments showed the decomposition of KBr5 into KBr3 (trigonal) and Br2 with a large volume reduction. First-principles structural searches were carried out to solve the composition and related crystal structures. The proposed structures give good description of the experimental Raman spectra and X-ray diffraction data. The electronic structure calculations reveal semiconducting behaviour for these compounds.
17 citations
TL;DR: Different types of hepatic TB have various imaging features that closely relates with pathological changes, and recognition and understanding the spectrum of CT features of hepatitis TB is helpful for the diagnosis; however, definitive diagnosis still depends on pathological examination.
6 citations
Journal Article•
2 citations
TL;DR: It is concluded that an auto-regulatory phosphatase network maintains epidermal homeostasis by controlling the onset and duration of commitment.
Abstract: Epidermal homeostasis depends on a balance between stem cell renewal and terminal differentiation1,2. While progress has been made in characterising the stem and differentiated cell compartments3, the transition between the two cell states, termed commitment4, is poorly understood. Here we characterise commitment by integrating transcriptomic and proteomic data from disaggregated primary human keratinocytes held in suspension for up to 12h. We have previously shown that commitment begins at approximately 4h and differentiation is initiated by 8h5. We find that cell detachment induces a network of protein phosphatases. The pro-commitment phosphatases, including DUSP6, PPTC7, PTPN1, PTPN13 and PPP3CA, promote terminal differentiation by negatively regulating ERK MAPK and positively regulating key AP1 transcription factors. Their activity is antagonised by concomitant upregulation of the anti-commitment phosphatase DUSP10. The phosphatases form a dynamic network of transient positive and negative interactions, with DUSP6 predominating at commitment. Boolean network modelling identifies a mandatory switch between two stable states (stem cell and differentiated cell) via an unstable (committed) state. In addition phosphatase expression is spatially regulated relative to the location of stem cells, both in vivo and in response to topographical cues in vitro. We conclude that an auto-regulatory phosphatase network maintains epidermal homeostasis by controlling the onset and duration of commitment.
01 Jan 2017
TL;DR: The case of mediastinitis in an adult individual, developed upon contiguous spread of oesophageal infection is document, because the presence of Prevotella oris, P. veroralis, Dialister pneumosintes, Klebsiella pneumoniae in tissue sample from mediast inum cannot be identified by standard culturing and Gram-staining.
Abstract: Here, we document the case of mediastinitis in an adult individual, developed upon contiguous spread of oesophageal infection. Our findings are noteworthy, because the presence of Prevotella oris , P. veroralis , Dialister pneumosintes , Klebsiella pneumoniae in tissue sample from mediastinum cannot be identified by standard culturing and Gram-staining. Importantly, however, 16S rDNA sequencing did lead to an unambiguous diagnosis and guided successful antimicrobial therapy.