A novel Pezizomycotina-specific protein with gelsolin domains regulates contractile actin ring assembly and constriction in perforated septum formation

Septum formation in fungi is equivalent to cytokinesis. It differs mechanistically in filamentous ascomycetes (Pezizomycotina) from that of ascomycete yeasts by the retention of a central septal pore in the former group. However, septum formation in both groups is accomplished by contractile actin ring (CAR) assembly and constriction. The specific components regulating septal pore organization during septum formation are poorly understood. In this study, a novel Pezizomycotina-specific actin regulatory protein GlpA containing gelsolin domains was identified using bioinformatics. A glpA deletion mutant exhibited increased distances between septa, abnormal septum morphology and defective regulation of septal pore closure. In glpA deletion mutant hyphae, overaccumulation of actin filament (F-actin) was observed, and the CAR was abnormal with improper assembly and failure in constriction. In wild-type cells, GlpA was found at the septum formation site similarly to the CAR. The N-terminal 329 residues of GlpA are required for its localization to the septum formation site and essential for proper septum formation, while its C-terminal gelsolin domains are required for the regular CAR dynamics during septum formation. Finally, in this study we elucidated a novel Pezizomycotina-specific actin modulating component, which participates in septum formation by regulating the CAR dynamics.     

Development of novel benzofuran-isatin conjugates as potential antiproliferative agents with apoptosis inducing mechanism in Colon cancer

In the current work, a new set of carbohydrazide linked benzofuran-isatin conjugates (5a–e and 7a–i) was designed and synthesised. The anticancer activity for compounds (5b–d, 7a, 7b, 7d and 7g) was measured against NCI-55 human cancer cell lines. Compound 5d was the most efficient, and thus subjected to the five-dose screen where it showed excellent broad activity against almost all tested cancer subpanels. Furthermore, all conjugates (5a–e and 7a–i) showed a good anti-proliferative activity towards colorectal cancer SW-620 and HT-29 cell lines, with an excellent inhibitory effect for compounds 5a and 5d (IC₅₀ = 8.7 and 9.4 µM (5a), and 6.5 and 9.8 µM for (5d), respectively). Both compounds displayed selective cytotoxicity with good safety profile. In addition, both compounds provoked apoptosis in a dose dependent manner in SW-620 cells. Also, they significantly inhibited the anti-apoptotic Bcl2 protein expression and increased the cleaved PARP level that resulted in SW-620 cells apoptosis.     

Effect of ethanol and zinc on ALA-dehydratase activity in red blood cells.

Subcutaneous injection of zinc as sulphate to rats activates sigma-aminolaevulinic acid dehydratase (ALA-D) in red blood cells within few days of injection. This activation counteracts the inhibitory effect of orally administered ethanol.     

Toll-like receptor-4 regulation of hepatic Cyp3a11 metabolism in a mouse model of LPS-induced CNS inflammation

Central nervous system (CNS) infection and inflammation severely reduce the capacity of cytochrome P-450 metabolism in the liver. We developed a mouse model to examine the effects of CNS inflammation on hepatic cytochrome P-450 metabolism. FVB, C57BL/6, and C3H/HeouJ mice were given Escherichia coli LPS (2.5 microg) by intracerebroventricular (ICV) injection. The CNS inflammatory response was confirmed by the elevation of TNF-alpha and/or IL-1beta proteins in the brain. In all mouse strains, LPS produced a 60-70% loss in hepatic Cyp3a11 expression and activity compared with saline-injected controls. Adrenalectomy did not prevent the loss in Cyp3a11 expression or activity, thereby precluding the involvement of the hypothalamic-adrenal-pituitary axis. Endotoxin was detectable (1-10 ng/ml) in serum between 15 and 120 min after ICV dosing of 2.5 microg LPS. Peripheral administration of 2.5 microg LPS by intraperitoneal injection produced similar serum endotoxin levels and a similar loss (60%) in Cyp3a11 expression and activity in the liver. The loss of Cyp3a11 in response to centrally or peripherally administered LPS could not be evoked in Toll-like receptor-4 (TLR4)-mutant (C3H/HeJ) mice, indicating that TLR4 signaling pathways are directly involved in the enzyme loss. In summary, we conclude that LPS is transferred from the brain to the circulation in significant quantities in a model of CNS infection or inflammation. Subsequently, LPS that has reached the circulation stimulates a TLR4-dependent mechanism in the periphery, evoking a reduction in Cyp3a11 expression and metabolism in the liver.     

Haematuria as a presentation of metastatic oesophageal carcinoma

Haematuria is a classical symptom of urological disease often signifying a primary bladder cancer. Rarely, however, the presence of blood in the urine can be due to secondary spread of tumours into the bladder from distant sites. Notably this has been reported to occur in breast cancer, malignant melanoma and gastric cancers. Haematuria due to spread from a primary oesophageal cancer to the bladder has never been reported. We present a case of haematuria confirmed histologically to be due to metastases from a primary oesophageal tumour. Oesophageal cancer is capable of spread to all three neighbouring compartments (abdomen, chest and neck) and therefore has the potential to spread to unusual sites. Clinicians should always carefully regard haematuria in a patient previously treated for cancer and retain a high index of suspicion for distant metastases as being the cause.     

Fine needle aspiration biopsy of azoospermic testes. Could it replace histologic biopsy?

OBJECTIVE: To evaluate the possibility of replacing histologic biopsy of azoospermic testes by fine needle aspiration (FNA) for diagnostic and management purposes. STUDY DESIGN: Twenty-seven patients were examined under general anesthesia, and 53 testes were biopsied by FNA. Fifty-four testes were biopsied for histologic examination. Histology and cytology of each testis were compared to assess the discrepancy or concordance between the diagnoses. RESULTS: Twenty-seven testes showed complete concordance of cytology and histology, and 13 testes showed a mild degree of discrepancy. A severe degree of discrepancy was seen in 13 testes. In the majority of discrepant cases, FNA biopsy diagnosis was more sensitive in detecting evidence of full or advanced maturation. In one case of discrepancy, the histologic finding was Sertoli cells only, and cytology revealed focal full maturation. In vitro fertilization using sperm from this case was successful. CONCLUSION: FNA biopsy of testes in azoospermia is a fast, reliable and minimally traumatic method. The prospects for utilizing FNA biopsy material in assisted and microassisted fertilization are promising.     

Cellularity of lobular carcinoma and its relationship to false negative fine needle aspiration results

OBJECTIVE: To evaluate the cytocellularity and histocellularity of lobular carcinoma (LC) and the relationship to high false negative results of fine needle aspiration cytology (FNAC). STUDY DESIGN: In this retrospective study, cellularity was studied in 60 cases of classic LC, LC variants and lobular carcinoma in situ, comparing cytologic smears to their corresponding histologic sections. The cytologic smears were grouped into acellular, low, moderate and high categories, and the histologic sections were grouped into low, moderate and high categories. RESULTS: Malignancy or suspicion of malignancy was diagnosed in 78% of cases. Overall cytocellularity showed acellularity or low cellularity in 60% of cases, while overall histocellularity showed moderate or high cellularity in 95% of cases. When the cytocellularity was moderate or high, the corresponding histocellularity always showed moderate or high histocellularity. When the cytocellularity was low, the corresponding histology showed low histocellularity in 6.3% of cases. Thus, in acellular and low cellular aspirations, corresponding histocellularity may not be the contributing factor toward low cellular yield. In this study, 22% of cases were diagnosed as false negative, 40% were diagnosed as suspicious, and 38% were called positive. Only 17% of positive cases were diagnosed as LC. A large number of LC were misdiagnosed by FNAC as duct cell carcinoma, and most cases of low histocellularity were of the classic type. CONCLUSION: The results of this study suggest that in the majority of cases of LC, cellular yield of FNAC is disproportionately lower than expected when compared to the corresponding histocellularity. Awareness of modest cellularity and subtle cytologic features will aid in the correct preoperative diagnosis of LC, and false negative diagnoses can be minimized.     

A Preliminary Study on Community Characteristics of Corticolous Lichen in Forest Ecosystem in Eastern Altay Mts .

In this paper, the authors used cluster analysis method to study the corticolous lichen community structure in forest ecosystem of eastern AltayMts of Xinjiang according to the on the spot investigation results in many year. The results show that in this Mts the lichen species which can be divided into four communities: (1 ) Calicium abietinum Pers + Tephromela atra (Hundson) community; (2) Leptogium saturninum (Dicks. ) + Lecidea elabens Fr. community; (3) Parmelia sulcata Tayl. apud Mack + Ramalina farnacea (L. ) Ach community; (4) Caloplaca flavorubescens + Phaeophyscia nigricans (Flk. ) community. We also were compared the species diversity, similarity and evenness index of differentcommunities.