Validation-based insertional mutagenesis (VBIM) technology identifies adenomatous polypossis coli (APC) like protein (ALP) as a novel negative regulator of NF-κB

Colorectal cancer (CRC) is the third leading cause of cancer related deaths in the United States. The nuclear factor κB (NF-κB) is an important family of transcription factors whose aberrant activation has been found in many types of cancer, including CRC. Therefore, understanding the regulation of NF-κB is of ultimate importance for cancer therapy. Using a novel validation-based insertional mutagenesis (VBIM) strategy, our lab has identified the novel adenomatous polyposis coli (APC) like protein (ALP) gene as a negative regulator of NF-κB. Preliminary studies from our lab demonstrated that overexpression of ALP led to decreased NF-κB activity by κB reporter assay and electrophoresis mobility gel shift assay (EMSA). The current project aims to further evaluate the role of ALP in the regulation of NF-κB signaling in CRC cells. We found that overexpression of ALP in human CRC HT29 cells greatly reduced both the number and the size of colonies that were formed in a soft agar assay. ALP overexpression also decreased the cell growth rate and cell migration ability, while shRNA mediated knockdown of ALP showed opposite effects, confirming that ALP is a tumor suppressor in CRC HT29 cells. Overexpression of ALP led to decreased NF-κB activity by κB reporter assay and condition media assay in CRC HT29 cells. Furthermore, immunohistochemical analysis with human colon vii tissues revealed that there is a gradual loss of ALP protein with tumor progression. We also found that ALP predominantly localizes in the cytoplasm, and binds to the p65 subunit of NF-κB, and might be functioning downstream of IκB kinase (IKK). In summary, in this study, we provide evidence regarding the tumor suppressor role of ALP in CRC by functioning as novel negative regulator of NF-κB. This discovery could lead to the establishment of ALP as a potential biomarker and therapeutic target in CRC

Erosion mitigation of lignosulfonate treated unstable soils

Highly unstable soils are common in many parts of the world. In recent years, traditional chemical admixtures such as cement, lime and fly ash were used for stabilising these soils. However, not all chemical stabilisers are readily acceptable due to stringent occupational health and safety issues and invariable change of soil pH that often limits the scope of vegetation plus imposing a threat to ground water pollution. However, recent research shows that lignosulfonate, an environmentally sustainable admixture, can stabilise unstable and erodible soils without causing adverse effects on the environment. This paper presents the results of a laboratory investigation and model predictions on the internal erosion behaviour of an unstable soil stabilised by lignosulfonate. Test results reveal that the erosion parameters such as the critical shear stress and coefficient of soil erosion were improved with the increased amount of lignosulfonate. A theoretical model has also been developed to capture the internal erosion behaviour of soil based on the law of conservation of energy. The stabilization of the soil particles by lignosulfonate treatment is characterized by the increased strain energy required to break the inter-particle bonds. The model predictions capture the internal erosion behaviour of lignosulfonate treated soil similar to the laboratory experiments

Microfilaria in malignant pleural effusion: an unusual incidental finding or causative association?

Lymphatic filariasis is common in tropical countries and is endemic in India. Filaria has a wide spectrum of presentation. Filarial lung involvement is usually in the form of tropical pulmonary eosinophilia with pulmonary infiltrates and peripheral eosinophilia. Filariasis presenting with pleural effusion is an unusual presentation. Malignancy in association with filarial pleural effusion is extremely rare and its role in tumorigenesis is controversial. In this context, we hereby report a case of 60 year old male, chronic smoker, who presented with left sided chest pain, cough, breathlessness, generalized weakness and swelling over left infrascapular region. Pleural fluid cytology repeated thrice due to degenerative changes, finally revealed malignant cells along with microfilaria. FNAC from left infrascapular swelling showed cytological features suggestive of metastatic deposits of Adenocarcinoma

Antidepressants for depression during pregnancy

The objectives are as follows: To assess the safety of antidepressant use, compared with placebo or psychological therapy, for the treatment of pre-existing and ante-natal depression during pregnancy. To assess the effectiveness of antidepressant use, compared with placebo or psychological therapy, for the treatment of pre-existing and ante-natal depression during pregnancy