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Dlx4 is a member of a family of homeobox genes with homology to Drosophila distal-less (dll) gene. We show that Dlx4 expression pattern partially overlaps with its cis-linked gene Dlx3 during mouse development as well as in neonatal and adult skin. In mice, Dlx4 is expressed in the branchial arches, embryonic limbs, digits, nose, hair follicle and in the basal and suprabasal layers of mouse interfollicular epidermis in neonatal and adult skin. We show that inactivation of Dlx4 in mice did not result in any overtly gross pathology. Skin development, homeostasis and response to TPA treatment was similar in mice with loss of Dlx4 compared to wild type counterparts.

Head and neck cancers (H&N) are a significant problem in our country constituting approximately one-third cancer cases in contrast to 4–5% in the developed world [1]. Men are more commonly affected than women and the incidence increases with age. Ninety-eight percent of the patients are over 40 years old. Squamous cell cancer constitutes the most common pathology and includes cancers of the oral cavity, oropharynx, larynx and hypopharynx, nasopharynx, nasal cavity, and paranasal sinuses. Non-squamous types include thyroid cancer, salivary gland cancer, and sarcomas. The two most common etiological factors of head and neck cancer are tobacco and alcohol. Because of the exposure to these carcinogens to the entire epithelium of the aerodigestive tract, patients with H&N cancers have more chance for developing second primaries. Other factors implicated include viruses, occupational agents, pollutants, diet, and genetic influences. Infection with carcinogenic types of human papillomavirus (HPV, especially type 16) is a risk factor, particularly for oropharynx cancers [2].

Epidermal-specific deletion of the homeobox transcription regulator DLX3 disrupts keratinocyte differentiation and results in an IL-17−linked psoriasis-like skin inflammation. To identify the epidermal initiating signals produced by DLX3-null keratinocytes, we performed acute deletion of DLX3 in adult epidermis using a tamoxifen-inducible Krt14-cre/ERT system. K14CreERT;DLX3fl/fl skin exhibited dysregulated expression of differentiation-associated genes, upregulation of proinflammatory cytokines, and accumulation of Langerhans cells and macrophages within 3 days of tamoxifen-induced DLX3 ablation. We also observed increased accumulation of IL-17A−secreting Vγ4 γδ T cells and heightened levels of IL-17 and IL-36 family of cytokines starting 1 week after DLX3 deletion. Interestingly, transcriptome profiling of K14CreERT;DLX3fl/fl epidermis at 3 days identified activated STAT3 as a transcriptional regulator and revealed differential expression of STAT3 signaling-related genes. Furthermore, activation of STAT3 was strongly increased in K14CreERT;DLX3fl/fl skin, and topical treatment with an inhibitor of STAT3 activation attenuated the immune phenotype. RNA-seq analysis of vehicle and STAT3 inhibitor treated K14CreERT;DLX3fl/fl skin identified differentially expressed genes associated with inhibition of leukocyte infiltration. Collectively, our results show that DLX3 is a critical regulator of STAT3 signaling network that maintains skin homeostasis.

Human IL11 is important for platelet recovery, especially after “chemotherapy-induced thrombocytopenia” through sequential interaction with IL-11Rα and gp130. JAK-STAT signal transduction gets activated for regulating platelet maturation. Earlier through wet-laboratory analyses, four mutations (R190E, R135E, L194D and I171D) were observed in IL11 to alter the binding process. Only R135E led to an increased affinity to bind IL11-Rα and gp130. This study focused on the evolutionary relatedness and residual conservation between the closely related species of IL11. Mutational impact in human due to I171V, which was observed in four species (Urocitellus parryii, Otolemur garnettii, Lagenorhynchus obliquidens and Delphinapterus leucas) in the multiple sequence alignment, was examined. The mutations other than isoleucine were observed to be highly conserved. All the mutations preserved protein functionality. An overall decreasing thermodynamic stability was inferred for the protein with mutations: I171D, R190E and L194D along-with a deleterious effect. Non-deleterious effect was observed for R135E mutation with a comparatively more stable Gibbs free energy. However, I171D, I171V, R135E and R190E occur in protein's binding sites and have the potential to alter ligand efficiency and other binding properties of IL11. Four documented mutations showed a transition from helices to coils whereas I171V did not cause any such transition. Phylogenetic tree of IL11 proteins demonstrated evolutionary divergence among IL11 proteins of land and water animals. Human IL11 was the most closely related to Urocitellus parryii, an arctic ground squirrel. Hyperagonistic mutation (R135E) shall be in the limelight for it can lead IL11 to act as an efficient thrombopoietic peptide.

Bronchogenic cysts are rare congenital malformations originating from budding of the tracheobronchial component during foregut development. Most cy sts are located in the mediastinum and the intrapulmonary region. Localization in the cervical area is unusual. The majority of cases have been reported in the pediatric population and few cases in adults. We report an unusual case of bronchogenic cyst presenting as a deep lateral neck mass with dysphagia in an adult female. This case presented with three unusual elements: adult female, lateral cervical location, and presence of symptoms.

Batch and column operations were performed utilizing thioglycolated sugarcane carbon (TSCC), a low-cost adsorbent, to remove As(III) and As(V) from aqueous systems. Under optimized batch conditions, the TSCC could remove up to 92.7 and 91.4 % for As(III) and As(V), respectively. An artificial neural network model showed the validity of TSCC as a preferable adsorbent for arsenic [As(III) and As(V)] removal in batch studies. In column operations, removal efficiency increases with increase in influent arsenic concentration and adsorbent dose and decreases with increase in flow rate. At an adsorbent dose of 6.0 g, flow rate 3.0 mL min−1, and initial arsenic concentration 1,500 μg L−1, the arsenic uptake capacity of TSCC for As(III) and As(V) was found to be 85.01 and 83.82 μg g−1, respectively. The Thomas model was used to analyze the column experimental data. Results from the column operations indicated that the adsorption behavior of arsenic [As(III) and As(V)] fits exceptionally well with the Thomas model with high correlation coefficient and very low standard error. Examinations of scanning electron microscopy and FTIR spectroscopy reveal that high arsenic adsorption favors surface complexation on the adsorbent surface.

Summary Epidermal morphogenesis results from a delicate balance between keratinocyte proliferation and differentiation, and this balance is perturbed upon deletion of transcription factor Ctip2. Here we demonstrate that Ctip2, in a cell autonomous manner, controls keratinocyte proliferation and cytoskeletal organization, and regulates the onset and maintenance of differentiation in keratinocytes in culture. Ctip2 integrates keratinocyte proliferation and the switch to differentiation by directly and positively regulating EGFR transcription in proliferating cells and Notch1 transcription in differentiating cells. In proliferative cells, the EGFR promoter is occupied by Ctip2, whereas Ctip2 is only recruited to the Notch1 promoter under differentiating conditions. Activation of EGFR signaling downregulates Ctip2 at the transcript level, whereas high calcium signaling triggers SUMOylation, ubiquitination and proteasomal degradation of Ctip2 at the protein level. Together, our findings demonstrate a novel mechanism(s) of Ctip2-mediated, coordinated control of epidermal proliferation and terminal differentiation, and identify a pathway of negative feedback regulation of Ctip2 during epidermal development.

Wnt pathway targeting is of high clinical interest for treating bone loss disorders such as osteoporosis. These therapies inhibit the action of negative regulators of osteoblastic Wnt signaling. The report that Wnt inhibitory factor 1 (WIF1) was epigenetically silenced via promoter DNA methylation in osteosarcoma (OS) raised potential concerns for such treatment approaches. Here we confirm that Wif1 expression is frequently reduced in OS. However, we demonstrate that silencing is not driven by DNA methylation. Treatment of mouse and human OS cells showed that Wif1 expression was robustly induced by HDAC inhibition but not by methylation inhibition. Consistent with HDAC dependent silencing, the Wif1 locus in OS was characterized by low acetylation levels and a bivalent H3K4/H3K27-trimethylation state. Wif1 expression marked late stages of normal osteoblast maturation and stratified OS tumors based on differentiation stage across species. Culture of OS cells under differentiation inductive conditions increased expression of Wif1. Together these results demonstrate that Wif1 is not targeted for silencing by DNA methylation in OS. Instead, the reduced expression of Wif1 in OS cells is in context with their stage in differentiation.

In this paper, an overview of the synthesis, chemistry and applications of nanosystems carried out in our laboratory is presented. The discussion is divided into four sections, namely (a) chemistry of nanoparticles, (b) development of new synthetic approaches, (c) gas phase clusters and (d) device structures and applications. In ‘chemistry of nanoparticles’ we describe a novel reaction between nanoparticles of Ag and Au with halocarbons. The reactions lead to the formation of various carbonaceous materials and metal halides. In ‘development of new synthetic approaches’ our one-pot methodologies for the synthesis of core-shell nanosystems of Au, Ag and Cu protected with TiO2 and ZrO2 as well as various polymers are discussed. Some results on the interaction of nanoparticles with biomolecules are also detailed in this section. The third section covers the formation of gas phase aggregates/clusters of thiol-protected sub-nanoparticles. Laser desorption of H2MoO4, H2WO4, MoS2, and WS2 giving novel clusters is discussed. The fourth section deals with the development of simple devices and technologies using nanomaterials described above.

Department of Microbiology, Lady Brabourne College, P-1/2, Suhrawardy Avenue, Kolkata-700 017, India E-mail : shreya84@gmail.com, for_rini_roy@yahoo.co.in post Graduate Department of Microbiology, Acharya Prafulla Chandra College, New Barrackpur, Kolkata-700 131, India E-mail: forsroy@yahoo.co.in Manuscript received 25 June 2008, revised 4 January 2010, accepted 25 February 2010 Cu has been used as an inducer or PcoC (SOD) in E. coli to screen the time for achieving maximum activity. This SOD can be isolated from bacterial system and purified to serve as a source for use in medicines for humans since SOD proteins or humans and E. coli share significant sequence similarity. Copper engulfment capacity of E. coli bas been utilised to induce PcoC (SOD) whichbas been measured by estimating the activity of the two proteins, PcoA and PcoC (Pco stands for plasmid borne copper resistance operon) withvariation In concentration of CuII in the medium and duration of incubation. CuII engulfment capacity of E. coli through liposome is greater in case of PcoC than PcoA.

Background COUP-TF interacting protein 2 [(Ctip2), also known as Bcl11b] is an important regulator of skin homeostasis, and is overexpressed in head and neck cancer. Ctip2ep−/− mice, selectively ablated for Ctip2 in epidermal keratinocytes, exhibited impaired terminal differentiation and delayed epidermal permeability barrier (EPB) establishment during development, similar to what was observed in Ctip2 null (Ctip2−/−) mice. Considering that as an important role of Ctip2, and the fact that molecular networks which underlie cancer progression partially overlap with those responsible for tissue remodeling, we sought to determine the role of Ctip2 during cutaneous wound healing. Methodology/Principal Findings Full thickness excisional wound healing experiments were performed on Ctip2L2/L2 and Ctip2ep−/− animals per time point and used for harvesting samples for histology, immunohistochemistry (IHC) and immunoblotting. Results demonstrated inherent defects in proliferation and migration of Ctip2 lacking keratinocytes during re-epithelialization. Mutant mice exhibited reduced epidermal proliferation, delayed keratinocyte activation, altered cell-cell adhesion and impaired ECM development. Post wounding, Ctip2ep−/− mice wounds displayed lack of E-Cadherin suppression in the migratory tongue, insufficient expression of alpha smooth muscle actin (alpha SMA) in the dermis, and robust induction of K8. Importantly, dysregulated expression of several hair follicle (HF) stem cell markers such as K15, NFATc1, CD133, CD34 and Lrig1 was observed in mutant skin during wound repair. Conclusions/Significance Results confirm a cell autonomous role of keratinocytic Ctip2 to modulate cell migration, proliferation and/or differentiation, and to maintain HF stem cells during cutaneous wounding. Furthermore, Ctip2 in a non-cell autonomous manner regulated granulation tissue formation and tissue contraction during wound closure.

Transcription factor CTIP2 (chicken ovalbumin upstream promoter transcription factor-interacting protein 2), also known as BCL11B, is expressed in hair follicles (HFs) of embryonic and adult skin. Ctip2-null mice exhibit reduced HF density during embryonic development. In contrast, conditional inactivation of Ctip2 in the epidermis ( Ctip2 ep-/- mice) leads to a shorter telogen and a premature entry into anagen during the second phase of hair cycling without a detectable change in the number of HFs. Keratinocytes of the bulge stem cells (SCs) niche of Ctip2 ep-/- mice proliferate more and undergo reduced apoptosis compared with the corresponding cells of wild-type mice. However, premature activation of follicular SCs in mice lacking CTIP2 leads to the exhaustion of this SC compartment in comparison with Ctip2 L2/L2 mice, which retained quiescent follicle SCs. CTIP2 modulates expression of genes encoding EGFR and NOTCH1 during formation of HFs and those encoding nuclear factor of activated T-cells cytoplasmic calcineurin-dependent 1 and LIM homeobox 2 during normal hair cycling in adult skin. The expression of most of these genes is disrupted in mice lacking CTIP2, and these alterations may underlie the phenotype of Ctip2-null and Ctip2 ep-/- mice. CTIP2 appears to serve as a transcriptional organizer that integrates input from multiple signaling cues during HF morphogenesis and hair cycling.