In Memory of Dr. Ratip Kazancıgil

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Dynamics of transcription factor binding site evolution

Evolution of gene regulation is crucial for our understanding of the phenotypic differences between species, populations and individuals. Sequence-specific binding of transcription factors to the regulatory regions on the DNA is a key regulatory mechanism that determines gene expression and hence heritable phenotypic variation. We use a biophysical model for directional selection on gene expression to estimate the rates of gain and loss of transcription factor binding sites (TFBS) in finite populations under both point and insertion/deletion mutations. Our results show that these rates are typically slow for a single TFBS in an isolated DNA region, unless the selection is extremely strong. These rates decrease drastically with increasing TFBS length or increasingly specific protein-DNA interactions, making the evolution of sites longer than ~10 bp unlikely on typical eukaryotic speciation timescales. Similarly, evolution converges to the stationary distribution of binding sequences very slowly, making the equilibrium assumption questionable. The availability of longer regulatory sequences in which multiple binding sites can evolve simultaneously, the presence of "pre-sites" or partially decayed old sites in the initial sequence, and biophysical cooperativity between transcription factors, can all facilitate gain of TFBS and reconcile theoretical calculations with timescales inferred from comparative genetics.Comment: 28 pages, 15 figure

Investigation of metallo beta lactamases and oxacilinases in carbapenem resistant acinetobacter baumannii strains isolated from inpatients

Background: Resistance to beta-lactam antibiotics is widespread among Acinetobacter strains. Plasmid-mediated metallo beta lactamases (MBL) are responsible for carbapenem resistance, as are oxacillinases (OXA). In recent years, MBL producing carbapenem-resistant strains have been reported in the world and in Turkey in increasing rates. In our country, besides the OXA 51- like enzyme which is inherent in A. baumannii strains, OXA 58-like and OXA 23-like carbapenemases producing strains have also been widely detected. In addition, Verona Imipenemase (VIM) and (IMP)-type MBL have been reported in some centers. Aims: The aim of our study was to investigate the presence of carbapenemases in Acinetobacter strains isolated from hospitalized patients in Edirne. Study Design: Cross-sectional study. Methods: A total of 52 imipenem-resistant A. baumannii strains isolated between January and March 2013 were investigated. The presence of MBL was described phenotypically by the combined disk diffusion test (CDDT), double disk synergy test (DDST), MBL E- test (only performed in 28 strains) and modified Hodge test. blaIMP , blaVIM, blaGIM, blaSIM, blaSPM genes and blaOXA-23, blaOXA-51, blaOXA-40, blaOXA-58 genes were inves- tigated by multiplex polymerase chain reaction (PCR). The blaNDM-1 gene was determined by PCR. Results: By modified Hodge test, 50 strains (96%) were found to be MBL positive. Positivity of MBL was 21% by both CDDT (0.1 M EDTA) and DDST. Twen- ty-four of 28 strains (85.7%) were positive by MBL E-test. OXA 23-like and OXA 51-like carbapenemases were detected in all strains, but OXA 58-like and OXA 40-like carbapenemases-producing A. baumannii were not detected. Also, MBL genes were not detected by genotypic methods. Conclusion: Only OXA 23-like carbapenemase was responsible for carbapenem resistance in carbapenem- resistant Acinetobacter strains in Edirne. The MBL- producing Acinetobacter strain is not yet a problem in our hospital. MBL resistance was found by phenotyp- ing tests, which must be confirmed by genotypic meth- ods; multiplex PCR tests can be easily used for screen- ing MBL

Simulation of annual plankton productivity cycle in the Black Sea by a one-dimensional physical-biological model

The annual cycle of the plankton dynamics in the central Black Sea is studied by a one-dimensional vertically resolved physical-biological upper ocean model, coupled with the Mellor-Yamada level 2.5 turbulence closure scheme. The biological model involves interactions between the inorganic nitrogen (nitrate, ammonium), phytoplankton and herbivorous zooplankton biomasses, and detritus. Given a knowledge of physical forcing, the model simulates main observed seasonal and vertical characteristic features, in particular, formation of the cold intermediate water mass and yearly evolution of the upper layer stratification, the annual cycle of production with the fall and the spring blooms, and the subsurface phytoplankton maximum layer in summer, as well as realistic patterns of particulate organic carbon and nitrogen. The computed seasonal cycles of the chlorophyll and primary production distributions over the euphotic layer compare reasonably well with the data. Initiation of the spring bloom is shown to be critically dependent on the water column stability. It commences as soon as the convective mixing process weakens and before the seasonal stratification of surface waters begins to develop. It is followed by a weaker phytoplankton production at the time of establishment of the seasonal thermocline in April. While summer nutrient concentrations in the mixed layer are low enough to limit production, the layer between the thermocline and the base of the euphotic zone provides sufficient light and nutrient to support subsurface phytoplankton development. The autumn bloom takes place some time between October and December depending on environmental conditions. In the case of weaker grazing pressure to control the growth rate, the autumn bloom shifts to December-January and emerges as the winter bloom or, in some cases, is connected with the spring bloom to form one unified continuous bloom structure during the January-March period. These bloom structures are similar to the year-to-year variabilities present in the data

Simulation of annual plankton productivity cycle in the Black Sea by a one-dimensional physical-biological model

The annual cycle of the plankton dynamics in the central Black Sea is studied by a one-dimensional vertically resolved physical-biological upper ocean model, coupled with the Mellor-Yamada level 2.5 turbulence closure scheme. The biological model involves interactions between the inorganic nitrogen (nitrate, ammonium), phytoplankton and herbivorous zooplankton biomasses, and detritus. Given a knowledge of physical forcing, the model simulates main observed seasonal and vertical characteristic features, in particular, formation of the cold intermediate water mass and yearly evolution of the upper layer stratification, the annual cycle of production with the fall and the spring blooms, and the subsurface phytoplankton maximum layer in summer, as well as realistic patterns of particulate organic carbon and nitrogen. The computed seasonal cycles of the chlorophyll and primary production distributions over the euphotic layer compare reasonably well with the data. Initiation of the spring bloom is shown to be critically dependent on the water column stability. It commences as soon as the convective mixing process weakens and before the seasonal stratification of surface waters begins to develop. It is followed by a weaker phytoplankton production at the time of establishment of the seasonal thermocline in April. While summer nutrient concentrations in the mixed layer are low enough to limit production, the layer between the thermocline and the base of the euphotic zone provides sufficient light and nutrient to support subsurface phytoplankton development. The autumn bloom takes place some time between October and December depending on environmental conditions. In the case of weaker grazing pressure to control the growth rate, the autumn bloom shifts to December-January and emerges as the winter bloom or, in some cases, is connected with the spring bloom to form one unified continuous bloom structure during the January-March period. These bloom structures are similar to the year-to-year variabilities present in the data

Comparison of two protective lung ventilatory regimes on oxygenation during one-lung ventilation: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>The efficacy of protective ventilation in acute lung injury has validated its use in the operating room for patients undergoing thoracic surgery with one-lung ventilation (OLV). The purpose of this study was to investigate the effects of two different modes of ventilation using low tidal volumes: pressure controlled ventilation (PCV) vs. volume controlled ventilation (VCV) on oxygenation and airway pressures during OLV.</p> <p>Methods</p> <p>We studied 41 patients scheduled for thoracoscopy surgery. After initial two-lung ventilation with VCV patients were randomly assigned to one of two groups. In one group OLV was started with VCV (tidal volume 6 mL/kg, PEEP 5) and after 30 minutes ventilation was switched to PCV (inspiratory pressure to provide a tidal volume of 6 mL/kg, PEEP 5) for the same time period. In the second group, ventilation modes were performed in reverse order. Airway pressures and blood gases were obtained at the end of each ventilatory mode.</p> <p>Results</p> <p>PaO₂, PaCO₂and alveolar-arterial oxygen difference did not differ between PCV and VCV. Peak airway pressure was significantly lower in PCV compared with VCV (19.9 ± 3.8 cmH₂O vs 23.1 ± 4.3 cmH₂O; p < 0.001) without any significant differences in mean and plateau pressures.</p> <p>Conclusions</p> <p>In patients with good preoperative pulmonary function undergoing thoracoscopy surgery, the use of a protective lung ventilation strategy with VCV or PCV does not affect the oxygenation. PCV was associated with lower peak airway pressures.</p

Delamination technique together with longitudinal incisions for treatment of Chiari I/syringomyelia complex: a prospective clinical study

<p>Abstract</p> <p>Background</p> <p>Treatment modalities in Chiari malformation type 1(CMI) accompanied by syringomyelia have not yet been standardized. Pathologies such as a small posterior fossa and thickened dura mater have been discussed previously. Various techniques have been explored to enlarge the foramen magnum and to expand the dura. The aim of this clinical study was to explore a new technique of excision of the external dura accompanied by widening the cisterna magna and making longitudinal incisions in the internal dura, without disturbing the arachnoid.</p> <p>Methods</p> <p>Ten patients with CMI and syringomyelia, operated between 2004 and 2006, formed this prospective series. All cases underwent foramen magnum decompression of 3 × 3 cm area with C1–C2 (partial) laminectomy, resection of foramen magnum fibrous band, excision of external dura, delamination and widening of internal dura with longitudinal incisions.</p> <p>Results</p> <p>Patients were aged between 25 and 58 years and occipital headache was the most common complaint. The mean duration of preoperative symptoms was 4 years and the follow-up time was 25 months. Clinical progression was halted for all patients; eight patients completely recovered and two reported no change. In one patient, there was a transient cerebrospinal fluid (CSF) fistula that was treated with tissue adhesive. While syringomyelia persisted radiologically with radiological stability in five patients; for three patients the syringomyelic cavity decreased in size, and for the remaining two it regressed completely.</p> <p>Conclusion</p> <p>Removal of the fibrous band and the outer dural layer, at level of foramen magnum, together with the incision of inner dural layer appears to be good technique in adult CMI patients. The advantages are short operation time, no need for duraplasty, sufficient posterior fossa decompression, absence of CSF fistulas as a result of extra arachnoidal surgery, and short duration of hospitalization. Hence this surgical technique has advantages compared to other techniques.</p