An example of secondary fault activity along the North Anatolian Fault on the NE Marmara Sea Shelf, NW Turkey

Seismic data on the NE Marmara Sea Shelf indicate that a NNE-SSW-oriented buried basin and ridge system exist on the sub-marine extension of the Paleozoic Rocks delimited by the northern segment of the North Anatolian Fault (NS-NAF), while seismic and multi-beam bathymetric data imply that four NW-SE-oriented strike-slip faults also exist on the shelf area. Seismic data indicate that NW-SE-oriented strike-slip faults are the youngest structures that dissect the basin-ridge system. One of the NW-SE-oriented faults (F1) is aligned with a rupture of the North Anatolian Fault (NAF) cutting the northern slope of the Cinarcik Basin. This observation indicates that these faults have similar characteristics with the NS-NAF along the Marmara Sea. Therefore, they may have a secondary relation to the NAF since the principle deformation zone of the NAF follows the Marmara Trough in that region. The seismic energy recorded on these secondary faults is much less than that on the NAF in the Marmara Sea. These faults may, however, produce a large earthquake in the long term

LH prevents cisplatin-induced apoptosis in oocytes and preserves female fertility in mouse

Premature ovarian failure and female infertility are frequent side effects of anticancer therapies, owing to the extreme sensitivity of the ovarian reserve oocytes to the damaging effects of irradiation and chemotherapy on DNA. We report here a robust protective effect of luteinizing hormone (LH) on the primordial follicle pool of prepubertal ovaries against the cisplatin (Cs)-induced apoptosis. In vitro LH treatment of prepubertal ovarian fragments generated anti-apoptotic signals by a subset of ovarian somatic cells expressing LH receptor (LHR) through cAMP/PKA and Akt pathways. Such signals, reducing the oocyte level of pro-apoptotic TAp63 protein and favoring the repair of the Cs-damaged DNA in the oocytes, prevented their apoptosis. Noteworthy, in vivo administration to prepubertal female mice of a single dose of LH together with Cs inhibited the depletion of the primordial follicle reserve caused by the drug and preserved their fertility in reproductive age, preventing significant alteration in the number of pregnancy and of delivered pups. In conclusion, these findings establish a novel ovoprotective role for LH and further support the very attracting prospective to use physiological 'fertoprotective' approaches for preventing premature infertility and risks linked to precocious menopause in young patients who survived cancer after chemotherapy

Evaluating susceptibility of karst dolines (sinkholes) for collapse in Sango, Tennessee, USA

Dolines or sinkholes are earth depressions that develop in soluble rocks complexes such as limestone, dolomite, gypsum, anhydrite, and halite; dolines appear in a variety of shapes from nearly circular to complex structures with highly curved perimeters. The occurrence of dolines in the studied karst area is not random; they are the results of geomorphic, hydrologic and chemical processes that have caused partial subsidence, even total collapse of the land surface, when voids and caves are present in the bedrock and the regolith arch overbridging these voids is unstable. In the study area, the majority of collapses occur in the regolith (bedrock cover) that bridges voids in the bedrock. Because these collapsing dolines can damage property and cause even the loss of lives, there is a need to develop methods for evaluating karst hazards; such methods can be used by planners and practitioners for urban and economic development, especially in regions with a growing population. The purpose of this project is threefold: 1) to develop a karst feature database, 2) to investigate critical indicators associated with doline collapse, and 3) to design a doline susceptibility model for potential doline collapse based on external morphometric data. The study revealed the presence of short range spatial dependence in the distribution of the dolines’ morphometric parameters such as circularity, geographic orientation of the main doline axes and the length-to-width doline ratios; therefore, geostatistics can be used to spatially evaluate the susceptibility of the karst area for doline collapse using the probability of occurrence of these critical parameters. The partial susceptibility estimates were combined into final spatial probabilities enabling the identification of areas where undetected dolines may cause significant hazards

Discovery of a small molecule antagonist of the parathyroid hormone receptor by using an N-terminal parathyroid hormone peptide probe

Once-daily s.c. administration of either human parathyroid hormone (PTH)-(1–84) or recombinant human PTH-(1–34) provides for dramatic increases in bone mass in women with postmenopausal osteoporosis. We initiated a program to discover orally bioavailable small molecule equivalents of these peptides. A traditional high-throughput screening approach using cAMP activation of the PTH/PTH-related peptide receptor (PPR) as a readout failed to provide any lead compounds. Accordingly, we designed a new screen for this receptor that used a modified N-terminal fragment of PTH as a probe for small molecule binding to the transmembrane region of the PPR, driven by the assumption that the pharmacological properties (agonist/antagonist) of compounds that bound to this putative signaling domain of the PPR could be altered by chemical modification. We developed DPC-AJ1951, a 14 amino acid peptide that acts as a potent agonist of the PPR, and characterized its activity in ex vivo and in vivo assays of bone resorption. In addition, we studied its ability to initiate gene transcription by using microarray technology. Together, these experiments indicated that the highly modified 14 amino acid peptide induces qualitatively similar biological responses to those produced by PTH-(1–34), albeit with lower potency relative to the parent peptide. Encouraged by these data, we performed a screen of a small compound collection by using DPC-AJ1951 as the ligand. These studies led to the identification of the benzoxazepinone SW106, a previously unrecognized small molecule antagonist for the PPR. The binding of SW106 to the PPR was rationalized by using a homology receptor model