Developmental divergence of sensory stimulus representation in cortical interneurons.

Vasocative-intestinal-peptide (VIP+) and somatostatin (SST+) interneurons are involved in modulating barrel cortex activity and perception during active whisking. Here we identify a developmental transition point of structural and functional rearrangements onto these interneurons around the start of active sensation at P14. Using in vivo two-photon Ca2+ imaging, we find that before P14, both interneuron types respond stronger to a multi-whisker stimulus, whereas after P14 their responses diverge, with VIP+ cells losing their multi-whisker preference and SST+ neurons enhancing theirs. Additionally, we find that Ca2+ signaling dynamics increase in precision as the cells and network mature. Rabies virus tracings followed by tissue clearing, as well as photostimulation-coupled electrophysiology reveal that SST+ cells receive higher cross-barrel inputs compared to VIP+ neurons at both time points. In addition, whereas prior to P14 both cell types receive direct input from the sensory thalamus, after P14 VIP+ cells show reduced inputs and SST+ cells largely shift to motor-related thalamic nuclei.

Evaluation of Matrix Metalloproteinases, Cytokines and Their Potential Role in the Development of Ovarian Cancer.

BACKGROUND: Ovarian cancer is the 5th most common cause of deaths in the women among gynecological tumors. There are many growing evidences that stress and other behavioral factors may affect cancer progression and patient survival. The purpose of this study is to determine the key role of matrix metalloproteinases (MMPs), and cytokines in the aggregation and progression of ovarian cancer. METHODOLOGY: Stress variables (MDA, AGEs, AOPPs, NO), profile of antioxidants (SOD, Catalase, Vitamin E & A, GSH, GRx, GPx) and inflammatory biomarkers (MMP-9, MMP-2, MMP-11, IL-1α and TNF-α) were biochemically assessed from venous blood of fifty ovarian cancer patients and twenty healthy control subjects. The results of all parameters were analyzed statistically by independent sample t-test. RESULTS: The results of the study demonstrated that the levels of stress variables like MDA (3.38±1.12nmol/ml), AGEs (2.72±0.22 ng/ml), AOPPs (128.48±27.23 ng/ml) and NO (58.71±8.67 ng/ml) were increased in the patients of ovarian cancer as compared to control individuals whereas the profile of antioxidants like SOD, Catalase, Vitamin E, Vitamin A, GSH and GRx were decreased in ovarian cancer patients (0.11±0.08 µg/ml, 2.41±1.01µmol/mol of protein, 0.22±0.04 µg/ml, 45.84±9.07µg/ml, 4.88±1.18µg/ml, 5.33±1.26 µmol/ml respectively). But the level of GPx antioxidant was increased in ovarian cancer patients (6.58±0.21µmol/ml). Moreover the levels of MMP-9 (64.87±5.35 ng/ml), MMP-2 (75.87±18.82 ng/ml) and MMP-11 (63.58±8.48 ng/ml) were elevated in the patients. Similarly, the levels of various cytokines TNF-α and IL-1α were also increased in the patients of ovarian cancer (32.17±3.52 pg/ml and 7.04±0.85 pg/ml respectively). CONCLUSION: MMPs are commonly expressed in ovarian cancer which are potential extrapolative biomarkers and have a major role in metastasis. Due to oxidative stress, different cytokines are released by tumor associated macrophages (TAMs) that result in the cancer progression. Consequently, tissue inhibitors of matrix metalloproteinases (TIMPs) are the valuable therapeutic approaches to complement conservative anticancer strategies.

A Novel Four-Way Complex Variant Translocation Involving Chromosome 46,XY,t(4;9;19;22)(q25:q34;p13.3;q11.2) in a Chronic Myeloid Leukemia Patient.

Philadelphia (Ph) chromosome (9;22)(q34;q11) is well established in more than 90% of chronic myeloid leukemia (CML) patients, and the remaining 5-8% of CML patients show variant and complex translocations, with the involvement of third, fourth, or fifth chromosome other than 9;22. However, in very rare cases, the fourth chromosome is involved. Here, we found a novel case of four-way Ph+ chromosome translocation involving 46,XY,t(4;9;19;22)(q25:q34;p13.3;q11.2) with CML in the chronic phase. Complete blood cell count of the CML patient was carried out to obtain total leukocytes count, hemoglobin, and platelets. Fluorescence in situ hybridization technique was used for the identification of BCR-ABL fusion gene, and cytogenetic test for the confirmation of Ph (9;22)(q34;q11) and the mechanism of variant translocation in the bone marrow. The patient is successfully treated with a dose of 400 mg/day imatinib mesylate (Gleevec). We observed a significant decrease in white blood cell count of 11.7 × 10(9)/L after 48-month follow-up. Patient started feeling better generally. There was a reduction in the swelling of the body, fatigue, and anxiety.