Mechanism of the Enzymic Reduction of N_2: The Binding of Adenosine 5'-Triphosphate and Cyanide to the N_2-reducing System

The in vitro reduction of N_2 is a complex process involving at least six different reactants: two proteins [1,2] for which the names azoferredoxin (AzoFd) and molybdoferredoxin (MoFd) have been proposed[3], an electron source, the electron acceptor, ATP[4], and Mg2+[5-7]. One of the goals of research in this area is to define the orderly and quantitative participation of these reactants leading to the reduction of the electron acceptor with concomitant breakdown of ATP to ADP and inorganic phosphate[7]. The work described in this paper shows that (1) AzoFd reversibly binds both ATP, a reactant in N2 reduction, and ADP, a specific inhibitor of N2 reduction, and (2) MoFd reversibly binds cyanide, which is also reduced by the N_2-reducing system. It is suggested that the binding of ATP and of cyanide are partial reactions of the N_2-reducing system

Super congruences and Euler numbers

Let $p>3$ be a prime. We prove that $$\sum_{k=0}^{p-1}\binom{2k}{k}/2^k=(-1)^{(p-1)/2}-p^2E_{p-3} (mod p^3),$$ $$\sum_{k=1}^{(p-1)/2}\binom{2k}{k}/k=(-1)^{(p+1)/2}8/3*pE_{p-3} (mod p^2),$$ $$\sum_{k=0}^{(p-1)/2}\binom{2k}{k}^2/16^k=(-1)^{(p-1)/2}+p^2E_{p-3} (mod p^3)$$, where E_0,E_1,E_2,... are Euler numbers. Our new approach is of combinatorial nature. We also formulate many conjectures concerning super congruences and relate most of them to Euler numbers or Bernoulli numbers. Motivated by our investigation of super congruences, we also raise a conjecture on 7 new series for $\pi^2$, $\pi^{-2}$ and the constant $K:=\sum_{k>0}(k/3)/k^2$ (with (-) the Jacobi symbol), two of which are $$\sum_{k=1}^\infty(10k-3)8^k/(k^3\binom{2k}{k}^2\binom{3k}{k})=\pi^2/2$$ and $$\sum_{k>0}(15k-4)(-27)^{k-1}/(k^3\binom{2k}{k}^2\binom{3k}k)=K.$

Semi-Quantitative Models for Identifying Potent and Selective Transthyretin Amyloidogenesis Inhibitors

Rate-limiting dissociation of the tetrameric protein transthyretin (TTR), followed by monomer misfolding and misassembly, appears to cause degenerative diseases in humans known as the transthyretin amyloidoses, based on human genetic, biochemical and pharmacologic evidence. Small molecules that bind to the generally unoccupied thyroxine binding pockets in the native TTR tetramer kinetically stabilize the tetramer, slowing subunit dissociation proportional to the extent that the molecules stabilize the native state over the dissociative transition state—thereby inhibiting amyloidogenesis. Herein, we use previously reported structure-activity relationship data to develop two semi-quantitative algorithms for identifying the structures of potent and selective transthyretin kinetic stabilizers/amyloidogenesis inhibitors. The viability of these prediction algorithms, in particular the more robust in silico docking model, is perhaps best validated by the clinical success of tafamidis, the first-in-class drug approved in Europe, Japan, South America, and elsewhere for treating transthyretin aggregation-associated familial amyloid polyneuropathy. Tafamidis is also being evaluated in a fully-enrolled placebo-controlled clinical trial for its efficacy against TTR cardiomyopathy. These prediction algorithms will be useful for identifying second generation TTR kinetic stabilizers, should these be needed to ameliorate the central nervous system or ophthalmologic pathology caused by TTR aggregation in organs not accessed by oral tafamidis administration

On the structure and function of nitrogenase from W5

Molybdoferredoxin from W5 was fractionated into MoFd with two atoms of molybdenum per 220,000 daltons and a specific activity of 2.6 [mu]moles C2H2 reduced/min/mg protein and into a catalytically inactive species with an identical protein moiety but an incomplete active centre. Native MoFd is a tetramer composed of two 50,000 and two 60,000 dalton subunits. At low protein concentrations the tetramer is in equilibrium with a dimer. Under low ionic strength and at low pH further dissociation into monomers occurs. MoFd and azoferredoxin have distinct electron paramagnetic resonance spectra. The EPR spectrum of AzoFd and that of the combination of the two nitrogenase components undergoes characteristic changes upon addition of MgATP2-.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34037/1/0000314.pd

Biological Imaging Capability in the ABRS Facility on ISS

This slide presentation reviews the Advanced Biological Research System (ABRS) on the International Space Station (ISS) and its biological imaging capability. The ABRS is an environmental control chamber. It has two indpendently controlled Experiment Research Chambers (ERCs) with temperature, relative humidity and carbon dioxide controls. ABRS is a third generation plant growth system. Several experiments are reviewed, with particular interest in the use of Green Fluorescent Protein (GFP) a non-destructive plant stress reporting mechanism, naturally found in jellyfish

Secondary structure of Ac-Alan_n-LysH+^+ polyalanine peptides (nn=5,10,15) in vacuo: Helical or not?

The polyalanine-based peptide series Ac-Ala_n-LysH+ (n=5-20) is a prime example that a secondary structure motif which is well-known from the solution phase (here: helices) can be formed in vacuo. We here revisit this conclusion for n=5,10,15, using density-functional theory (van der Waals corrected generalized gradient approximation), and gas-phase infrared vibrational spectroscopy. For the longer molecules (n=10,15) \alpha-helical models provide good qualitative agreement (theory vs. experiment) already in the harmonic approximation. For n=5, the lowest energy conformer is not a simple helix, but competes closely with \alpha-helical motifs at 300K. Close agreement between infrared spectra from experiment and ab initio molecular dynamics (including anharmonic effects) supports our findings.Comment: 4 pages, 4 figures, Submitted to JPC Letter

Specific orofacial problems experienced by musicians

Background: Patients who play musical instruments (especially wind and stringed instruments) and vocalists are prone to particular types of orofacial problems. Some problems are caused by playing and some are the result of dental treatment. This paper proposes to give an insight into these problems and practical guidance to general practice dentists. Method: Information in this paper is gathered from studies published in dental, music and occupational health journals, and from discussions with career musicians and music teachers. Results: Orthodontic problems, soft tissue trauma, focal dystonia, denture retention, herpes labialis, dry mouth and temporomandibular joint (TMJ) disorders were identified as orofacial problems of career musicians. Options available for prevention and palliative treatment as well as instrument selection are suggested to overcome these problems. Conclusions: Career musicians express reluctance to attend dentists who are not sensitive to their specific needs. General practitioner dentists who understand how the instruments impact on the orofacial structures and are aware of potential problems faced by musicians are able to offer preventive advice and supportive treatment to these patients, especially those in the early stages of their career