Integrated stratigraphy of the Priabonian (upper Eocene) Urtsadzor section, Armenia

The transition from the Bartonian to the Priabonian, as traditionally understood, has long been associated with a series of extinctions and originations in several microfossil groups. The planktonic foraminifer genus Morozovelloides and large species of Acarinina suffered a rapid global extinction, as did many radiolarians. Calcareous nannofossils show several assemblage changes including the acme beginning of Cribrocentrum erbae and the lowest and highest occurrences of Chiasmolithus oamaruensis and C. grandis respectively. In shallow water environments, larger foraminifera also show an extinction among large species of Nummulites, as well as the first occurrences of the stratigraphically important genus Spiroclypeus. However, the correlation between shallow and deep water records remains uncertain, as do the mechanisms driving these biotic events. Here we present the results of a new integrated stratigraphical study (calcareous nannofossils, planktonic foraminifera, larger benthic foraminifera, and low-resolution magnetostratigraphy) of the Urtsadzor section in south-western Armenia which appears to be continuous through this interval. The Urtsadzor section consists of calcareous siltstones rich in micro- and nannofossils, with interbedded limestones containing abundant larger benthic foraminifera. Our new data enable us to correlate larger foraminiferal events with global plankton biostratigraphy, in a section outside of southwest Europe where most previous correlations have been based. At Urtsadzor, the large Nummulites species of N. millecaput-group are present throughout the whole section but decrease in abundance toward the top. The first occurrence of Spiroclypeus, also occurs in the upper part of the section, marking the SBZ 18/19 boundary. These events are associated with the phylogenetic development of the Nummulites fabianii and Heterostegina reticulata lineages. However, the calcareous plankton biostratigraphy indicates the section is well within the Priabonian; within planktonic foraminiferal Zones E14 and E15 and calcareous nannoplankton Zones CNE 18 and CNE 19. These results indicate larger foraminiferal events occur well above the planktonic foraminiferal extinction level and nannofossil assemblage changes indicating the events are not synchronous across groups, with implications for biostratigraphy and recognition of the basal Priabonian in different depositional settings and regions

GERMLINE GAIN-OF-FUNCTION MUTATIONS of ALK DISRUPT CENTRAL NERVOUS SYSTEM DEVELOPMENT

International audienceNeuroblastoma (NB) is a frequent embryonal tumour of sympathetic ganglia and adrenals with extremely variable outcome. Recently, somatic amplification and gain-of-function mutations of the anaplastic lymphoma receptor tyrosine kinase (ALK, MIM 105590) gene, either somatic or germline, were identified in a significant proportion of NB cases. Here we report a novel syndromic presentation associating congenital NB with severe encephalopathy and abnormal shape of the brainstem on brain MRI in two unrelated sporadic cases harbouring de novo, germline, heterozygous ALK gene mutations. Both mutations are gain-of-function mutations that have been reported in NB and NB cell lines. These observations further illustrate the role of oncogenes in both tumour predisposition and normal development, and shed light on the pleiotropic and activity-dependent role of ALK in humans. More generally, missing germline mutations relative to the spectrum of somatic mutations reported for a given oncogene may be a reflection of severe effects during embryonic development, and may prompt mutation screening in patients with extreme phenotypes

Tumor Invasion of Salmonella enterica Serovar Typhimurium Is Accompanied by Strong Hemorrhage Promoted by TNF-α

BACKGROUND:Several facultative anaerobic bacteria with potential therapeutic abilities are known to preferentially colonize solid tumors after systemic administration. How they efficiently find and invade the tumors is still unclear. However, this is an important issue to be clarified when bacteria should be tailored for application in cancer therapy. METHODOLOGY/PRINCIPAL FINDINGS:We describe the initial events of colonization of an ectopic transplantable tumor by Salmonella enterica serovar Typhimurium. Initially, after intravenous administration, bacteria were found in blood, spleen, and liver. Low numbers were also detected in tumors associated with blood vessels as could be observed by immunohistochemistry. A rapid increase of TNF-alpha in blood was observed at that time, in addition to other pro-inflammatory cytokines. This induced a tremendous influx of blood into the tumors by vascular disruption that could be visualized in H&E stainings and quantified by hemoglobin measurements of tumor homogenate. Most likely, together with the blood, bacteria were flushed into the tumor. In addition, blood influx was followed by necrosis formation, bacterial growth, and infiltration of neutrophilic granulocytes. Depletion of TNF-alpha retarded blood influx and delayed bacterial tumor-colonization. CONCLUSION:Our findings emphasize similarities between Gram-negative tumor-colonizing bacteria and tumor vascular disrupting agents and show the involvement of TNF-alpha in the initial phase of tumor-colonization by bacteria

Spin density studies on p-O2NC6F4CNSSN: A heavy p-block organic ferromagnet

A complete picture of the spin density distribution in the organic radical p-O2NC6F4CNSSN has been obtained by a combination of polarized neutron diffraction, electron paramagnetic resonance (EPR), and electron-nuclear double resonance (ENDOR) spectroscopies, and ab initio density-functional theory (DFT) calculations. Polarized neutron diffraction revealed that the spin distribution is predominantly localized on the N and S atoms (+0.25μB and +0.28μB, respectively) of the heterocyclic ring with a small negative spin density on the heterocyclic C atom (−0.06μB). These spin populations are in excellent agreement with both ab initio DFT calculations (spin populations on the C, N, and S sites of −0.07, 0.22 and 0.31, respectively) and cw-EPR studies which estimated the spin population on the N site as 0.24. The DFT calculated spin density revealed less than 1% spin delocalization onto the perfluoroaryl ring, several orders of magnitude lower than the density on the heterocyclic ring. cw-ENDOR studies at both X-band (9 GHz) and Q-band (34 GHz) frequencies probed the spin populations on the two chemically distinct F atoms. These spin populations on the F atoms ortho and meta to the dithiadiazolyl ring are of magnitude 10−3 and 10−4, respectively

Application of prolonged microdialysis sampling in carboplatin-treated cancer patients

Purpose: To better understand the mechanisms underlying (in)sensitivity of tumors to anticancer drugs, assessing intra-tumor drug pharmacokinetics (PKs) could be important. We explored the feasibility of microdialysis in tumor tissue for multiple days in a clinical setting, using carboplatin as model drug. Methods: Plasma and microdialysate samples from tumor and adipose normal tissues were collected up to 47 h after dosing in eight carboplatin-treated patients with an accessible (sub)cutaneous tumor. Results: Pharmacokinetics were evaluable in tumor tissue in 6/8 patients and in adipose normal tissue in 3/8 patients. Concentration-time curves of unbound platinum in both the tissues followed the pattern of the curves in plasma, with exposure ratios of tissue versus plasma ranging from 0.64 to 1.46. Conclusions: Microdialysis can be successfully employed in ambulant patients for multiple days, which enables one to study tissue PK of anticancer drugs in normal and malignant tissues in more detail