Interaction Between Motor Domains Can Explain the Complex Dynamics of Heterodimeric Kinesins

Motor proteins are active enzyme molecules that play a crucial role in many biological processes. They transform the chemical energy into the mechanical work and move unidirectionally along rigid cytoskeleton filaments. Single-molecule experiments suggest that motor proteins, consisting of two motor domains, move in a hand-over-hand mechanism when each subunit changes between trailing and leading positions in alternating steps, and these subunits do not interact with each other. However, recent experiments on heterodimeric kinesins suggest that the motion of motor domains is not independent, but rather strongly coupled and coordinated, although the mechanism of these interactions are not known. We propose a simple discrete stochastic model to describe the dynamics of homodimeric and heterodimeric two-headed motor proteins. It is argued that interactions between motor domains modify free energy landscapes of each motor subunit, and motor proteins still move via the hand-over-hand mechanism but with different transitions rates. Our calculations of biophysical properties agree with experimental observations. Several ways to test the theoretical model are proposed.Comment: To appear in New J. Phy

An abdominal tuberculosis case mimicking an abdominal mass

Abdominal tuberculosis is rare in childhood. It may be difficult to diagnose as it mimics various disorders. We present a 12-year-old child with an unusual clinical presentation who was diagnosed with abdominal tuberculosis only perioperatively

A new type of Na+-driven ATP synthase membrane rotor with a two-carboxylate ion-coupling motif

Abstract: The anaerobic bacterium Fusobacterium nucleatum uses glutamate decarboxylation to generate a transmembrane gradient of Na+. Here, we demonstrate that this ion-motive force is directly coupled to ATP synthesis, via an F1Fo-ATP synthase with a novel Na+ recognition motif, shared by other human pathogens. Molecular modeling and free-energy simulations of the rotary element of the enzyme, the c-ring, indicate Na+ specificity in physiological settings. Consistently, activity measurements showed Na+ stimulation of the enzyme, either membrane-embedded or isolated, and ATP synthesis was sensitive to the Na+ ionophore monensin. Furthermore, Na+ has a protective effect against inhibitors targeting the ion-binding sites, both in the complete ATP synthase and the isolated c-ring. Definitive evidence of Na+ coupling is provided by two identical crystal structures of the c11 ring, solved by X-ray crystallography at 2.2 and 2.6 Å resolution, at pH 5.3 and 8.7, respectively. Na+ ions occupy all binding sites, each coordinated by four amino acids and a water molecule. Intriguingly, two carboxylates instead of one mediate ion binding. Simulations and experiments demonstrate that this motif implies that a proton is concurrently bound to all sites, although Na+ alone drives the rotary mechanism. The structure thus reveals a new mode of ion coupling in ATP synthases and provides a basis for drug-design efforts against this opportunistic pathogen. Author Summary: Essential cellular processes such as biosynthesis, transport, and motility are sustained by the energy released in the hydrolysis of ATP, the universal energy carrier in living cells. Most ATP in the cell is produced by a membrane-bound enzyme, the ATP synthase, through a rotary mechanism that is coupled to the translocation of ions across the membrane. The majority of ATP synthases are energized by transmembrane electrochemical gradients of protons (proton-motive force), but a number of organisms, including some important human pathogens, use gradients of sodium ions instead (sodium-motive force). The ion specificity of ATP synthases is determined by a membrane-embedded sub-complex, the c-ring, which is the smallest known biological rotor. The functional mechanism of the rotor ring and its variations among different organisms are of wide interest, because of this enzyme's impact on metabolism and disease, and because of its potential for nanotechnology applications. Here, we characterize a previously unrecognized type of Na+-driven ATP synthase from the opportunistic human pathogen Fusobacterium nucleatum, which is implicated in periodontal diseases. We analyzed this ATP synthase and its rotor ring through a multi-disciplinary approach, combining cell-growth and biochemical assays, X-ray crystallography and computer-simulation methods. Two crystal structures of the membrane rotor were solved, at low and high pH, revealing an atypical ion-recognition motif mediated by two carboxylate side-chains. This motif is shared by other human pathogens, such as Mycobacterium tuberculosis or Streptococcus pneumonia, whose ATP synthases are targets of novel antibiotic drugs. The implications of this ion-recognition mode on the mechanism of the ATP synthase and the cellular bioenergetics of F. nucleatum were thus examined. Our results provide the basis for future pharmacological efforts against this important pathogen

The hot core towards the intermediate mass protostar NGC7129 FIRS 2: Chemical similarities with Orion KL

NGC 7129 FIRS 2 (hereafter FIRS 2) is an intermediate-mass (2 to 8 Msun) protostar located at a distance of 1250 pc. High spatial resolution observations are required to resolve the hot core at its center. We present a molecular survey from 218200 MHz to 221800 MHz carried out with the IRAM Plateau de Bure Interferometer. These observations were complemented with a long integration single-dish spectrum taken with the IRAM 30m telescope. We used a Local Thermodynamic Equilibrium (LTE) single temperature code to model the whole dataset. The interferometric spectrum is crowded with a total of ~300 lines from which a few dozens remain unidentified yet. The spectrum has been modeled with a total of 20 species and their isomers, isotopologues and deuterated compounds. Complex molecules like methyl formate (CH3OCHO), ethanol (CH3CH2OH), glycolaldehyde (CH2OHCHO), acetone (CH3COCH3), dimethyl ether (CH3OCH3), ethyl cyanide (CH3CH2CN) and the aGg' conformer of ethylene glycol (aGg'-(CH2OH)_2) are among the detected species. The detection of vibrationally excited lines of CH3CN, CH3OCHO, CH3OH, OCS, HC3N and CH3CHO proves the existence of gas and dust at high temperatures. In fact, the gas kinetic temperature estimated from the vibrational lines of CH3CN, ~405 K, is similar to that measured in massive hot cores. Our data allow an extensive comparison of the chemistry in FIRS~2 and the Orion hot core. We find a quite similar chemistry in FIRS 2 and Orion. Most of the studied fractional molecular abundances agree within a factor of 5. Larger differences are only found for the deuterated compounds D2CO and CH2DOH and a few molecules (CH3CH2CN, SO2, HNCO and CH3CHO). Since the physical conditions are similar in both hot cores, only different initial conditions (warmer pre-collapse phase in the case of Orion) and/or different crossing time of the gas in the hot core can explain this behavior.Comment: 30 pages, 9 figure

Non-equilibrium oxidation states of zirconium during early stages of metal oxidation

The chemical state of Zr during the initial, self-limiting stage of oxidation on single crystal zirconium (0001), with oxide thickness on the order of 1 nm, was probed by synchrotron x-ray photoelectron spectroscopy. Quantitative analysis of the Zr 3d spectrum by the spectrum reconstruction method demonstrated the formation of Zr[superscript 1+], Zr[superscript 2+], and Zr[superscript 3+] as non-equilibrium oxidation states, in addition to Zr[superscript 4+] in the stoichiometric ZrO2. This finding resolves the long-debated question of whether it is possible to form any valence states between Zr[superscript 0] and Zr[superscript 4+] at the metal-oxide interface. The presence of local strong electric fields and the minimization of interfacial energy are assessed and demonstrated as mechanisms that can drive the formation of these non-equilibrium valence states of Zr.United States. Department of Energy. Office of Basic Energy Sciences(Contract No. DE-AC02-98CH10886

Bimodal Phase Diagram of the Superfluid Density in LaAlO3/SrTiO3 Revealed by an Interfacial Waveguide Resonator

We explore the superconducting phase diagram of the two-dimensional electron system at the LaAlO3/SrTiO3 interface by monitoring the frequencies of the cavity modes of a coplanar waveguide resonator fabricated in the interface itself. We determine the phase diagram of the superconducting transition as a function of temperature and electrostatic gating, finding that both the superfluid density and the transition temperature follow a dome shape, but that the two are not monotonically related. The ground state of this 2DES is interpreted as a Josephson junction array, where a transition from long- to short-range order occurs as a function of the electronic doping. The synergy between correlated oxides and superconducting circuits is revealed to be a promising route to investigate these exotic compounds, complementary to standard magneto-transport measurements.Comment: 5 pages, 4 figures and 10 pages of supplementary materia

Determination of trace elements in the plants of Mt. Bozdag, Izmir, Turkey

The aim of this study was to determine the current level of atmospheric heavy metal content on the Bozdag Mountain of the Aegean Region, Turkey. Twenty nine different plants were selected to study their potential as biomonitors of trace elements such as Ni, Zn, Fe, Pb, Mn and Cd (μg g-1, dry weight). The samples were collected from two different altitudes of Mt. Bozdag. The concentrations of trace elements were determined by atomic absorption spectrometry. The mean concentrations determined at 1000 m altitude ranged from 0.025 to 1.609, 0.232 to 0.731, 0.578 to 5.983, 0.287 to 0.565 and 0.176 to 2.659 (μg g-1, dry weight), for Ni, Zn, Fe, Pb and Mn, respectively. At the altitude of 1600 m, the values ranged from 0.023 to 0.939, 0.258 to 1.254, 0.839 to 5.176, 0.301 to 1.341 and 0.405 to 3.351 (μg g-1, dry weight) for Ni, Zn, Fe, Pb and Mn, respectively. No Cd was detected at either altitude. Statistical significance was determined by the independent sample t-test and comparisons were made in order to determine if there were any differences between the averages of herbaceous and woody plants.

A comparative study on the abundance and elemental composition of POM in three interconnected basins: the Black, the Marmara and the Mediterranean Seas

The abundance and elemental composition of suspended particulate organic matter in the upper layers of the interconnected Mediterranean, Marmara and Black Seas having different ecosystems were determined in 1990-1998. The aim was principally to compare the C:N:P ratio of seston and understand factors controlling the seston composition in near- and off-shore waters of these seas. In the Marmara Sea, euphotic zone average particulate concentrations varied regionally and seasonally between 10-35 ìM for POC, 0.4-4.5 ìM for PON and 0.05-0.45 ìM for PP. These concentrations are mostly above the off-shore Black Sea values but much greater than those measured in the open waters of the north-eastern Mediterranean whose near-shore data are comparable with the seston content of the deep Black Sea. Comparison of C:N:P ratios of seston reveals that atmospheric and land-based phosphorus input influences the C:P and N:P ratios in the near-shore waters. Apparent nutrient deficiencies observed in the water column were not as remarkable in the elemental composition of seston. Unexpectedly, in the NE Mediterranean, N:P ratios from regression analyses of particulate data are very low (7-9) in the coastal region but slightly increase to levels of 10-15 in the open sea. In the Sea of Marmara, the N:P ratios (7-12) of seston are as low as in the Mediterranean, being consistent with the particulate ratios of the Black Sea inflow and NO3:PO4 ratios of the Marmara sub-halocline water. The Black Sea seston is relatively rich in carbonaceous compounds with N:P ratio ranging merely between 15-17 in the open sea but 9-27 in coastal waters where riverine discharges markedly influence the stoichiometry of seston

Evaluation of left renal vein and inferior vena cava variations through routine abdominal multi-slice computed tomography

Background: The aim of this study was to evaluate the frequency of left renal vein (LRV) and inferior vena cava (IVC) variations and the effect of gender on this frequency, as well as the presence of associated abdominal pathologies.Materials and methods: Multi-slice computed tomography (MSCT) images from 746 patients were evaluated retrospectively.Results: Left renal vein variations were identified in 9.8% of cases, while retroaortic LRV (RLRV) and circumaortic LRV (CLRV) were found in 7.4% and 2.4% of cases, respectively. No significant correlation was found between gender and LRV variations (p = 0.797). Of the cases with LRV and IVC variations, 73% had abdominal pathologies, the most common of which were nephrolithiasis, which appeared in 18 (32%) cases, and renal cysts, which appeared in 14 (25.4%) cases.Conclusions: MSCT is a rapid and reliable method of identifying LRV and IVC variations and associated abdominal pathologies