The DNA-recognition mode shared by archaeal feast/famine-regulatory proteins revealed by the DNA-binding specificities of TvFL3, FL10, FL11 and Ss-LrpB

The DNA-binding mode of archaeal feast/famine-regulatory proteins (FFRPs), i.e. paralogs of the Esherichia coli leucine-responsive regulatory protein (Lrp), was studied. Using the method of systematic evolution of ligands by exponential enrichment (SELEX), optimal DNA duplexes for interacting with TvFL3, FL10, FL11 and Ss-LrpB were identified as TACGA[AAT/ATT]TCGTA, GTTCGA[AAT/ATT]TCGAAC, CCGAAA[AAT/ATT]TTTCGG and TTGCAA[AAT/ATT]TTGCAA, respectively, all fitting into the form abcdeWWWedcba. Here W is A or T, and e.g. a and a are bases complementary to each other. Apparent equilibrium binding constants of the FFRPs and various DNA duplexes were determined, thereby confirming the DNA-binding specificities of the FFRPs. It is likely that these FFRPs recognize DNA in essentially the same way, since their DNA-binding specificities were all explained by the same pattern of relationship between amino-acid positions and base positions to form chemical interactions. As predicted from this relationship, when Gly36 of TvFL3 was replaced by Thr, the b base in the optimal DNA duplex changed from A to T, and, when Thr36 of FL10 was replaced by Ser, the b base changed from T to G/A. DNA-binding characteristics of other archaeal FFRPs, Ptr1, Ptr2, Ss-Lrp and LysM, are also consistent with the relationship

Estrogen receptor transcription and transactivation: Estrogen receptor alpha and estrogen receptor beta - regulation by selective estrogen receptor modulators and importance in breast cancer

Estrogens display intriguing tissue-selective action that is of great biomedical importance in the development of optimal therapeutics for the prevention and treatment of breast cancer, for menopausal hormone replacement, and for fertility regulation. Certain compounds that act through the estrogen receptor (ER), now referred to as selective estrogen receptor modulators (SERMs), can demonstrate remarkable differences in activity in the various estrogen target tissues, functioning as agonists in some tissues but as antagonists in others. Recent advances elucidating the tripartite nature of the biochemical and molecular actions of estrogens provide a good basis for understanding these tissue-selective actions. As discussed in this thematic review, the development of optimal SERMs should now be viewed in the context of two estrogen receptor subtypes, ERα and ERβ, that have differing affinities and responsiveness to various SERMs, and differing tissue distribution and effectiveness at various gene regulatory sites. Cellular, biochemical, and structural approaches have also shown that the nature of the ligand affects the conformation assumed by the ER-ligand complex, thereby regulating its state of phosphorylation and the recruitment of different coregulator proteins. Growth factors and protein kinases that control the phosphorylation state of the complex also regulate the bioactivity of the ER. These interactions and changes determine the magnitude of the transcriptional response and the potency of different SERMs. As these critical components are becoming increasingly well defined, they provide a sound basis for the development of novel SERMs with optimal profiles of tissue selectivity as medical therapeutic agents

Molecular studies on the factors controlling the anionic polymer composition of the cell wall of Bacillus subtilis

Available from British Library Document Supply Centre-DSC:DXN030780 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

Thick strip method for efficient large-eddy simulations of flexible wings in stall

An efficient computational method is presented based on the thick strip method for Large-Eddy simulation of flexible wings in stall. Fluid domain is break down into series of smaller 3k strips which one independently solved using implicit LES method. Force and moments are obtained from each strips and used to evolved the nonlinear dynamics of the structure. High deformation response of high-altitude long-endurance wing under several angle of attacks leading to the stall regions are presented to show the capability of proposed FSI method

The Life Time Prevalence of Childhood Seizure

"nBackground: Seizure is the most common pediatric neurologic disorder. Epidemiological studies of childhood epilepsy are of importance to compare incidence and prevalence rates, age distribution, inheritance, seizure types, epilepsy syn­dromes and treatment strategies. Since there is little information about prevalence of childhood seizure in Iran, this study was aimed to determine the life time prevalence of childhood seizure and some of its determining factors in Tehran, Iran."nMethods: In this cross sectional study, 2500 male and female students, aged 12 years or younger, studying in fifth grade of primary schools in district one of Ministry of Education were assessed by filling a preliminary questionnaire. Those who were categorized by the author as having a history of any form of seizure were assessed by a second questionnaire. The clinical form of seizure, the presumptive cause, positive family history and use of anti-convulsant drugs were recorded."nResults: The life time prevalence of seizure was 32/1000 population which was more prevalent in boys .Generalized seizure was the most common clinical form. Approximately 60% of cases reported febrile convulsion as the presumptive cause stated by the physician. Positive family history was reported in 29.6% of cases. Anti epileptic drugs were taken by 54% of students with a positive history of seizure."nConclusion: The results of this study show that the life time prevalence of seizure is relatively high in Iranian community, although the other factors were in concordance with other communities

Chlorotoxin and Lung Cancer: A Targeting Perspective for Drug Delivery

In the generational evolution of nano-based drug delivery carriers, active targeting has been a major milestone for improved and selective drug accumulation in tissues and cell types beyond the existing passive targeting capabilities. Among the various active targeting moieties, chlorotoxin, a peptide extracted from scorpions, demonstrated promising tumor cell accumulation and selection. With lung cancer being among the leading diagnoses of cancer-related deaths in both men and women, novel therapeutic methodologies utilizing nanotechnology for drug delivery emerged. Given chlorotoxin’s promising biological activity, we explore its potential against lung cancer and its utilization for active targeting against this cancer’s tumor cells. Our analysis indicates that despite the extensive chlorotoxin’s research against glioblastoma, lung cancer research with the molecule has been limited, despite some promising early results