DNA photodamage recognition by RNA polymerase II.

During gene transcription, RNA polymerase (Pol) II encounters obstacles, including lesions in the DNA template. Here, we review a recent structure–function analysis of Pol II transcribing DNA with a bulky photo-lesion in the template strand. The study provided the molecular basis for recognition of a damaged DNA by Pol II, which is the first step in transcription-coupled DNA repair (TCR). The results have general implications for damage recognition and the TCR mechanism.http://dx.doi.org

Monitoring of Cell Layer Integrity with a Current-Driven Organic Electrochemical Transistor

The integrity of CaCo-2 cell barriers is investigated by organic electrochemical transistors (OECTs) in a current-driven configuration. Ion transport through cellular barriers via the paracellular pathway is modulated by tight junctions between adjacent cells. Rupturing its integrity by H2O2 is monitored by the change of the output voltage in the transfer characteristics. It is demonstrated that by operating the OECT in a current-driven configuration, the sensitive and temporal resolution for monitoring the cell barrier integrity is strongly enhanced as compared to the OECT transient response measurement. As a result, current-driven OECTs are useful tools to assess dynamic and critical changes in tight junctions, relevant for clinical applications as drug targeting and screening

CPD damage recognition by transcribing RNA polymerase II.

Cells use transcription-coupled repair (TCR) to efficiently eliminate DNA lesions such as ultraviolet light–induced cyclobutane pyrimidine dimers (CPDs). Here we present the structure-based mechanism for the first step in eukaryotic TCR, CPD-induced stalling of RNA polymerase (Pol) II. A CPD in the transcribed strand slowly passes a translocation barrier and enters the polymerase active site. The CPD 5′-thymine then directs uridine misincorporation into messenger RNA, which blocks translocation. Artificial replacement of the uridine by adenosine enables CPD bypass; thus, Pol II stalling requires CPD-directed misincorporation. In the stalled complex, the lesion is inaccessible, and the polymerase conformation is unchanged. This is consistent with nonallosteric recruitment of repair factors and excision of a lesion-containing DNA fragment in the presence of Pol II

Elaia, Pergamon's maritime satellite:The rise and fall of an ancient harbour city shaped by shoreline migration

Throughout human history, communication and trade have been key to society. Because maritime trade facilitated the rapid transportation of passengers and freight at relatively low cost, harbours became hubs for traffic, trade and exchange. This general statement holds true for the Pergamenian kingdom, which ruled wide parts of today's western Turkey during Hellenistic times. Its harbour, located at the city of Elaia on the eastern Aegean shore, was used extensively for commercial and military purposes. This study reconstructs the coastal evolution in and around the ancient harbour of Elaia and compares the observed environmental modifications with archaeological and historical findings. We use micropalaeontological, sedimentological and geochemical proxies to reconstruct the palaeoenvironmental dynamics and evolution of the ancient harbour. The geoarchaeological results confirm the archaeological and historical evidence for Elaia's primacy during Hellenistic and early Roman times, and the city's gradual decline during the late Roman period. Furthermore, our study demonstrates that Elaia holds a unique position as a harbour city during ancient times in the eastern Aegean region, because it was not greatly influenced by the high sediment supply associated with river deltas. Consequently, no dredging of the harbour basins is documented, creating exceptional geo-bioarchives for palaeoenvironmental reconstructions

The Metal-Insulator Transition of the Magneli phase V_4O_7: Implications for V_2O_3

The metal-insulator transition (MIT) of the Magneli phase V_4O_7 is studied by means of electronic structure calculations using the augmented spherical wave method. The calculations are based on density functional theory and the local density approximation. Changes of the electronic structure at the MIT are discussed in relation to the structural transformations occuring simultaneously. The analysis is based on a unified point of view of the crystal structures of all Magneli phase compounds V_nO_2n-1 (3 =< n =< 9) as well as of VO_2 and V_2O_3. This allows to group the electronic bands into states behaving similar to the dioxide or the sesquioxide. In addition, the relationship between the structural and electronic properties near the MIT of these oxides can be studied on an equal footing. For V_4O_7, a strong influence of metal-metal bonding across octahedral faces is found for states both parallel and perpendicular to the hexagonal c_hex axis of V_2O_3. Furthermore, the structural changes at the MIT cause localization of those states, which mediate in-plane metal-metal bonding via octahedral edges. This band narrowing opens the way to an increased influence of electronic correlations, which are regarded as playing a key role for the MIT of V_2O_3.Comment: 7 pages, 3 figures, more information at http://www.physik.uni-augsburg.de/~eyert

Mechanism of transcriptional stalling at cisplatin-damaged DNA.

The anticancer drug cisplatin forms 1,2-d(GpG) DNA intrastrand cross-links (cisplatin lesions) that stall RNA polymerase II (Pol II) and trigger transcription-coupled DNA repair. Here we present a structure-function analysis of Pol II stalling at a cisplatin lesion in the DNA template. Pol II stalling results from a translocation barrier that prevents delivery of the lesion to the active site. AMP misincorporation occurs at the barrier and also at an abasic site, suggesting that it arises from nontemplated synthesis according to an 'A-rule' known for DNA polymerases. Pol II can bypass a cisplatin lesion that is artificially placed beyond the translocation barrier, even in the presence of a GdotA mismatch. Thus, the barrier prevents transcriptional mutagenesis. The stalling mechanism differs from that of Pol II stalling at a photolesion, which involves delivery of the lesion to the active site and lesion-templated misincorporation that blocks transcription

Analyzing the neocortical fine-structure

Cytoarchitectonic fields of the human neocortex are defined by characteristic variations in the composition of a general six-layer structure. It is commonly accepted that these fields correspond to functionally homogeneous entities. Diligent techniques were developed to characterize cytoarchitectonic fields by staining sections of post-mortem brains and subsequent statistical evaluation. Fields were found to show a considerable interindividual variability in extent and relation to macroscopic anatomical landmarks. With upcoming new high-resolution magnetic resonance imaging (MRI) protocols, it appears worthwhile to examine the feasibility of characterizing the neocortical fine-structure from anatomical MRI scans, thus, defining neocortical fields by in vivo techniques. A fixated brain hemisphere was scanned at a resolution of approximately 0.3 mm. After correcting for intensity inhomogeneities in the dataset, the cortex boundaries (the white/grey matter and grey matter/background interfaces) were determined as a triangular mesh. Radial intensity profiles following the shortest path through the cortex were computed and characterized by a sparse set of features. A statistical similarity measure between features of different regions was defined, and served to define the extent of Brodmann’s Areas 4, 17, 44 and 45 in this dataset

The high-intensity hyperon beam at CERN

A high-intensity hyperon beam was constructed at CERN to deliver Sigma- to experiment WA89 at the Omega facility and operated from 1989 to 1994. The setup allowed rapid changeover between hyperon and conventional hadron beam configurations. The beam provided a Sigma-flux of 1.4 x 10^5 per burst at mean momenta between 330 and 345 Gev/c, produced by about 3 x 10^10 protons of 450 GeV/c . At the experiment target the beam had a Sigma-/pi- ratio close to 0.4 and a size of 1.6 x 3.7 cm^2. The beam particle trajectories and their momenta were measured with a scintillating fibre hodoscope in the beam channel and a silicon microstrip detector at the exit of the channel. A fast transition radiation detector was used to identify the pion component of the beam.Comment: 20 pages, 13 figures. Submitted to Nucl. Instr. Meth.