Effect of tea catechins on tRNA structure and dynamics

Abbreviations C catechin

ECG epicatechin gallate

EGCG Epigallocatechin gallate

A Adenine

C cytosine

G Guanine

U uracil

FTIR Fourier transform infrared

Communicated by Ramaswamy H. Sarma     

Ligand-based pharmacophore mapping and virtual screening for identification of potential discoidin domain receptor 1 inhibitors

Abbreviations ADME absorption, distribution, metabolism, and excretion

MMGB/SA molecular mechanics generalized born surface area

IFD induced fit docking

RTK receptor tyrosine kinase

NSCLC non-small-cell lung cancer

ATP adenosine triphosphate

OPLS optimized potential for liquid stimulation

RMSD root mean square deviation

HTVS high-throughput virtual screening

SP standard precision

XP extra precision

OPLS-AA optimized potential for liquid stimulation-all atom

MD molecular simulation

MME molecular mechanics energies

SGB surface generalized born

POPC membrane 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine membrane

PDB Protein Data Bank

DDR1 discoidin domain receptor 1

DDR2 discoidin domain receptor 2

DDRs discoidin domain receptors

ECM extracellular matrix

TIP4P transferable intermolecular potential 4 point

NPT constant particle number, pressure and temperature

RMSF root mean square fluctuation

Communicated by Ramaswamy H. Sarma     

Vorinostat,a possible alternative to metronidazole for the treatment of amebiasis caused by Entamoeba histolytica

Abbreviations SAHA suberoylanilide hydroxamic acid

EhHDAC Histone Deacetylase from Entamoeba histolytica

Rg Radius of gyration

RMSD root-mean-square deviation

RMSF root-mean-square fluctuation

MDS molecular dynamics simulation

VMD Visual Molecular Dynamics

NAMD Nanoscale Molecular Dynamics

PBC periodic boundary conditions

PME Particle Mesh Ewald

3D three-dimensional

Cα alpha carbon

FDA Food and Drug Administration

ns nanoseconds

GPU CUDA Graphics Processing Unit Compute Unified Device Architecture

Communicated by Ramaswamy H. Sarma     

Children Make their Own Movies

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Making Things Book 2 by Ann Wiseman Little, Brown and Company $4.95.

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Snow Sculpture and Ice Carving by James Haskins Collier Books $4.95.     

Molecular dynamics simulation studies on influenza A virus H5N1 complexed with sialic acid and fluorinated sialic acid

Abbreviations HA Hemagglutinin

MD Molecular Dynamics

MM-PBSA Molecular Mechanics Poisson–Boltzmann Surface Area

NA Neuraminidase

NAMD Nanoscale Molecular Dynamic Simulation

PMEMD Particle Mesh Ewald Molecular Dynamics

RMSD Root-Mean-Square Deviation

RMSF Root-Mean-Square Fluctuation

SIA sialic acid

VMD Visual Molecular Dynamics

Communicated by Ramaswamy H. Sarma     

Successional pathways of Mediterranean evergreen vegetation on Sicily

The Mediterranean evergreen vegetation of Sicily, comprised in the belt of the Quercetea ilicis, occupies a large part of the island. Human intervention (cutting, fire, pasture) has brought about a degradation of the natural vegetation. This study is based on our phytosociological research of the Quercetea ilicis belt on Sicily.

With the ‘habitat comparison’ method, the dynamical relations between the different vegetation units have been defined.

We distinguish the following stages, with reference to their vegetation structure:

• a herbaceous stage formed by steppic vegetation, preceded by various types of nitrophilous-ruderal vegetation on abandoned fields;

• a garrigue stage dominated by half-shrubs;

• a macquis stage with various distinct plant communities, four communities being important in regressive successions, and three in progressive ones;

• a woodland and shrub-woodland stage with three different substages: pre-existent forests, present woodlands, and woodlands which tend towards the final, stable stage of vegetation (potential natural vegetation).

The dynamic relationships both in progressive and regressive successions have been synthesized in a scheme. In this scheme we have shown the main stages of the vegetation in their dynamics and we have constructed different series of vegetation types in two altitudinal belts, which are determined by varying environmental conditions of today.

The results also show that in some cases the progressive series follow different pathways than the regressive series, and the final stage of the progressive series is different from the original vegetation.

     

Short Notes

Food of the Common Gull on grassland in autumn and winter, by J. D. R. Vernon

Prey taken by Short-eared Owls at British breeding sites and winter quarters, by David E. Glue

The bill-lengths of Dunlins, by John Griffiths

The timing of the moults of the Pied Wagtail, by G. K. Baggott

Iris colour in the Hen Harrier, by E. Balfour

Sexing Oystercatchers from bill measurements, by P. B. Heppleston and D. F. Kerridge

Swallows in Wing-moult in Southern Spain, by S. L. Pimm     

Structural dynamics behind variants in pyrazinamidase and pyrazinamide resistance

Abstract

Pyrazinamide (PZA) is an important component of first-line anti-tuberculosis (anti-TB) drugs. The anti-TB agent is activated into an active form, pyrazinoic acid (POA), by Mycobacterium tuberculosis (MTB) pncA gene encoding pyrazinamidase (PZase). The major cause of PZA-resistance has been associated with mutations in the pncA gene. We have detected several novel mutations including V131F, Q141P, R154T, A170P, and V180F (GeneBank Accession No. MH461111) in the pncA gene of PZA-resistant isolates during PZA drug susceptibility testing followed by pncA gene sequencing. Here, we investigated molecular mechanism of PZA-resistance by comparing the results of experimental and molecular dynamics. The mutants (MTs) and wild type (WT) PZase structures in apo and complex with PZA were subjected to molecular dynamic simulations (MD) at the 40?ns. Multiple factors, including root mean square deviations (RMSD), binding pocket, total energy, dynamic cross correlation, and root mean square fluctuations (RMSF) of MTs and WT were compared. The MTs attained a high deviation and fluctuation compared to WT. Binding pocket volumes of the MTs, were found, lower than the WT, and the docking scores were high than WT while shape complementarity scores were lower than that of the WT. Residual motion in MTs are seemed to be dominant in anti-correlated motion. Mutations at locations, V131F, Q141P, R154T, A170P, and V180F, might be involved in the structural changes, possibly affecting the catalytic property of PZase to convert PZA into POA. Our study provides useful information that will enhance the understanding for better management of TB. Abbreviations DST drug susceptibility testing

Δelec electrostatic energy

LJ Lowenstein–Jensen medium

MGIT mycobacterium growth indicator tubes

MTs mutants

MD molecular dynamic simulations

MTB Mycobacterium tuberculosis

NALC–NaOH N-acetyl-l-cysteine–sodium hydroxide

NIH National Institutes of Health

NPT amount of substance (N), pressure (P) temperature (T)

NVT moles (N), volume (V) temperature (T)

PZase pyrazinamidase

Δps polar solvation energy

PTRL Provincial Tuberculosis Reference Laboratory

RMSD root mean square deviations

RMSF root mean square fluctuations

ΔSASA solvent accessible surface area energy

TB tuberculosis

GTotal total binding free energy

ΔvdW Van der Waals energy

WT wild type

Communicated by Ramaswamy H. Sarma     

Soft regions of protein surface are potent for stable dimer formation

Abstract

By having knowledge about the characteristics of protein interaction interfaces, we will be able to manipulate protein complexes for therapies. Dimer state is considered as the primary alphabet of the most proteins’ quaternary structure. The properties of binding interface between subunits and of noninterface region define the specificity and stability of the intended protein complex. Considering some topological properties and amino acids’ affinity for binding in interfaces of protein dimers, we construct the interface-specific recurrence plots. The data obtained from recurrence quantitative analysis, and accessibility-related metrics help us to classify the protein dimers into four distinct classes. Some mechanical properties of binding interfaces are computed for each predefined class of the dimers. The computed mechanical characteristics of binding patch region are compared with those of nonbinding region of proteins. Our observations indicate that the mechanical properties of protein binding sites have a decisive impact on determining the dimer stability. We introduce a new concept in analyzing protein structure by considering mechanical properties of protein structure. We conclude that the interface region between subunits of stable dimers is usually mechanically softer than the interface of unstable protein dimers. Abbreviations AAB average affinity for binding

ANM anisotropic network model

APC affinity propagation clustering

ASA accessible surface area

CCD inter residues distance

CSC complex stability code

DM distance matrix

ΔG_diss PISA-computed dissociation free energy

GNM Gaussian normal mode analysis

NMA normal mode analysis

PBP protein binding patch

PISA proteins, interfaces, structures and assemblies

rASA relative accessible area in respect to unfolded state of residues

RM recurrence matrix

rP relative protrusion

RP recurrence plot

RQA recurrence quantitative analysis

SEM standard error of mean

Communicated by Ramaswamy H. Sarma     

Site-specific metastasis formation

The metastatic spread of tumors is a well-coordinated process in which different types of

cancers tend to form metastases in defined organs. The formation of site-specific metastases

requires full compatibility between the intrinsic properties of the tumor cells and the tumor

microenvironment. It was recently found that chemokines which are expressed in specific loci

promote the adhesion, migration and invasion of tumor cells that express the corresponding

receptor/s. Of the different members of the family, the CXCL12 chemokine and its cognate

CXCR4 receptor are the prototypes of this process, although other members of the family (e.g.

CCR7 and CCR10) also play a role in determination of the metastatic spread. This commentary

addresses the fundamental roles of chemokines and their receptors in site-specific metastasis,

with emphasis on CXCL12-CXCR4. The article also describes some of the efforts that were

performed thus far in order to identify the intracellular components involved in this process. The

focus is put on the roles played by proteins that regulate adhesion and migration of tumor cells

in response to CXCL12, including mainly Focal Adhesion Kinase, Pyk2/RAFTK and members of

the Rho family of GTPases (RhoA, Rac, Cdc42). This is followed by discussion of open

questions that need to be addressed in future research, and of the potential therapeutic

implications of the findings that are available to date in this field.     

Inhibitory effects of persistent apoptotic cells on monoclonal antibody production in vitro

Cells undergoing apoptosis in vivo are rapidly detected and cleared by phagocytes. Swift

recognition and removal of apoptotic cells is important for normal tissue homeostasis

and failure in the underlying clearance mechanisms has pathological consequences

associated with inflammatory and auto-immune diseases. Cell cultures in vitro usually

lack the capacity for removal of non-viable cells because of the absence of phagocytes

and, as such, fail to emulate the healthy in vivo micro-environment from which dead cells

are absent. While a key objective in cell culture is to maintain viability at maximal levels,

cell death is unavoidable and non-viable cells frequently contaminate cultures in

significant numbers. Here we show that the presence of apoptotic cells in monoclonal

antibody-producing hybridoma cultures has markedly detrimental effects on antibody

productivity. Removal of apoptotic hybridoma cells by macrophages at the time of

seeding resulted in 100% improved antibody productivity that was, surprisingly to us,

most pronounced late on in the cultures. Furthermore, we were able to recapitulate this

effect using novel super-paramagnetic Dead-Cert?Nanoparticles to remove non-viable

cells simply and effectively at culture seeding. These results (1) provide direct evidence

that apoptotic cells have a profound influence on their non-phagocytic neighbours in

culture and (2) demonstrate the effectiveness of a simple dead-cell removal strategy for

improving antibody manufacture in vitro.     

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Watercolor Landscape Reinhold, Publisher Rex Brandt List price: $10.00.     

Evolutionary significance and functional characterization of streptomycin adenylyltransferase from Serratia marcescens

Abstract

Complete functional annotations of proteins are essential to understand the role and mechanisms in pathogenesis. Aminoglycoside nucleotidyltransferases are the subclasses of aminoglycosides modifying enzymes conferring resistance to organisms. Insight into the structural and functional understanding of nucleotidyltransferase family protein provides vital information to combat pathogenesis. Phylogenetic analysis is employed to identify the evolutionary significance and common motif’s present among the homologs of nucleotidyltransferase family protein. Structure, sequence based approaches and molecular docking were implemented to predict the exact function of the protein. Wide distribution of the nucleotidyltransferase family protein in gram-positive and gram-negative organisms are evidenced from phylogenetic analysis. Five common motifs were present in all the homolog’s of nucleotidyltransferase family protein. Sequence-structure based functional annotations predicts that the targeted protein function as ATP-Mg dependent streptomycin adenylyltransferase. Structural comparisons and docking studies correlate well with the identified function. The complete function of nucleotidyltransferase family protein was identified as Streptomycin adenylyltransferase and it could be targeted as a potential therapeutic target to overcome antibiotic resistance.

Communicated by Ramaswamy H. Sarma

Abbreviations AAC aminoglycoside acetyltransferases

AME aminoglycoside modifying enzyme

ANT aminoglycoside nucleotidyltransferases

APH aminoglycoside phosphotransferases

ATP adenosine triphosphate

CASTp computer atlas and surface topography of proteins

DUF domains of unknown function

Glide grid-based ligand docking with energetic

HMM hidden Markov model

MAST motif alignment and search tool

MEGA molecular evolutionary genetics analysis

MEME multiple Em for motif elicitation

MSA multiple sequence alignment

NMP nucleoside monophosphate

NTP nucleoside triphosphate

NT nucleotidyltransferase

OPLS optimized potential for liquid simulation

XP extra precision

     

Dodecamers derived from the crystal structure were found in the pre-crystallization solution of the transaminase from the thermophilic bacterium Thermobaculum terrenum by small-angle X-ray scattering

Abstract

The pre-crystallization solution of the transaminase from Thermobaculum terrenum (TaTT) has been studied by small-angle X-ray scattering (SAXS). Regular changes in the oligomeric composition of the protein were observed after the addition of the precipitant. Comparison of the observed oligomers with the crystal structure of TaTT (PDB ID 6GKR) shows that dodecamers may act as building blocks in the growth of transaminase single crystals. Correlating of these results to the similar X-ray studies of other proteins suggests that SAXS may be a valuable tool for searching optimum crystallization conditions. Abbreviation SAXS small-angle X-ray scattering

Ta transaminase

TaTT transaminase from Thermobaculum terrenum

PLP pyridoxal-5’-phosphate

R-PEA R-(þ)-1-phenylethylamine

BCAT branched-chain amino acid aminotransferase

DAAT D-aminoacid aminotransferase

R-TA R-amine:pyruvate transaminase

Communicated by Ramaswamy H. Sarma     

An Eighth Grade Art Appreciation Activity

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Film Making in Creative Teaching Watson-Guptill Publications List Price $8.95. Reviewed by Keith Kennedy.     

The pathogenicity,structural and functional exploration of human HMGB1 single nucleotide polymorphisms using in silico study

Abstract

The human HMGB1 gene mutations have a major impact on several immune-related diseases and cancer. The detrimental effect of non-synonymous mutations of HMGB1 has not been investigated yet, hence the present study aims to examine single nucleotide polymorphisms and their implications on the structure-function of human HMGB1. The multifaceted HMGB1 protein acts as pleiotropic cytokine and regulates essential genes for coordinated cellular functions. The mutational effect on HMGB1 was analyzed by sequence-based homology methods, supervised learning methods, and structure-based methods. The study identified 58 non-synonymous mutations in human HMGB1, out of which only 2 mutations; R10T (rs61742222) and F103C (rs61733675) were classified as the SNPs with highest deleterious and disease-causing mutants. The effect of these mutations in structure of HMGB1 was scrutinized and the R10T mutant found to have a distinct structural behaviour in the B-box domain. In addition, R10T mutant predicted that it affects the MoRF function of HMGB1 and it could disrupt the DNA binding or/and protein partner interaction activity by HMGB1. F103C mutation takes place at the TLR binding and cytokine inducing region of HMGB1, hence it could affect the protein binding activity which involves in many cellular signaling. The study identified potent mutations R10T (a cancer-causing somatic mutation) and F103C (a novel mutation) and these mutations either directly or indirectly hinder DNA binding activity and TLR and cytokine binding of HMGB1. These findings will help in understanding the molecular basis of these promising mutations and functional role of human HMGB1 in cancer and immunological diseases.

Abbreviations AGER Advanced glycosylation end product-specific receptor

CXCL Chemokine (C-X-C motif) ligand

dbSNP The single nucleotide polymorphism database

HMGB1 High mobility group box 1

LINCS LINear Constraint Solver

MDS Molecular dynamics simulation

MoRF Molecular recognition features

NPT Number of particle, Pressure and Temperature

NVT Number of particle, Volume and Temperature

nsSNP Non-synonymous SNP

PBC Partial boundary condition

PCA Principal component analysis

PME Partial mesh Ewald

RMSD Root mean square deviation

RMSF Root mean square fluctuation

SNP Single nucleotide polymorphism

SPC Single-point charge

TLR Toll-like receptor

UTR Un-translated Region

Communicated by Ramaswamy H. Sarma     

Bidirectional control of the inner dynamics of focal adhesions promotes cell migration

Focal adhesions (FA) are bidirectional mechanical biosensors that allow cells to integrate

intracellular and extracellular cues. Their function is tightly regulated by changes in

molecular composition and also by variation in the spatio-temporal dynamics of FA

components within this structure. A closely regulated turnover of FA proteins within FA

sites allows cells to respond appropriately to their environment, thereby impacting on cell

shape and function. FA protein dynamics are linked to FA maturation and rates of

assembly and disassembly, and have a significant influence on tumor cell migration.

Using the FRAP technique to investigate the hidden internal dynamics of FA, we

identified two new regulators of FA dynamics and cell migration: the Mgat5/galectin-3

lattice and tyrosine phosphorylated caveolin-1 (pY14Cav1). In this short review we first

introduce FA and their complex dynamic behavior. We then present the Mgat5/galectin-3

lattice and caveolin-1 and discuss their concerted role in FA dynamics, which defines

previously unknown, interdependent roles in tumor cell migration. We conclude with a

discussion of interesting unexplored avenues that might lead to a better understanding of

the complex mechanism of FA dynamics.     

Complexation of cis-Pt and trans-Pt(NH3)2Cl2 with serum proteins: A potential application for drug delivery

Abbreviations HAS human serum albumin

BSA bovine serum albumin

β-LG beta-lactoglobulin

cis-Pt and trans-Pt Pt(NH₃)₂Cl₂

FTIR Fourier transform infrared

Communicated by Ramaswamy H. Sarma