The biological functions of low-frequency vibrations (phonons) 5. A phenomenological theory

Low-frequency internal motions of a biomacromolecule are thought to possess significant biological function from the dynamic point of view. In this paper, a general phenomenological theory is established by which it is clearly verified that low-frequency resonance plays a central role in the energy transmission required during the cooperative interaction between subunits in a protein oligomer. According to the present theory, it is found that the energy transmission between a pair of diagonal subunits in a protein oligomer with a polygon arrangement is the most efficient, so as to in a sense further predict that after a ligand is bound to a subunit by random collision, its diagonal subunit in the same protein oligomer will possess the greatest probability of binding with the next ligand. Furthermore, based on the concept of the 'resonance-controlled trigger' derived from the phenomenological theory, it is feasible to estimate the lower time limit of allosteric transition from one subunit to the other. Such a time limit depends on the dominant low-frequency mode of each subunit, the ratio of the coupling force constant to the corresponding inherent force constant, as well as the geometrical arrangement of subunits in a protein oligomer. So far none of the allosteric transitions observed in proteins has exceeded the time limit as defined here, indicating a logical consistency between our theory and the experiments.     

Characterization of the Psychological,Physiological and EEG Profile of Acute Betel Quid Intoxication in Na?ve Subjects

Betel quid use and abuse is wide spread in Asia but the physiological basis of intoxication and addiction are unknown. In subjects naïve to the habit of betel quid intoxication, the psychological and physiological profile of intoxication has never been reported. We compared the effect of chewing gum or chewing betel quid, and subsequent betel quid intoxication, on psychological assessment, prospective time interval estimation, numerical and character digit span, computerized 2 choice tests and mental tasks such as reading and mathematics with concurrent monitoring of ECG, EEG and face temperature in healthy, non-sleep deprived, male subjects naïve to the habit of chewing betel quid. Betel quid intoxication, dose dependently induced tachycardia (max 30 bpm) and elevated face temperature (0.7°C) (P<0.001) above the effects observed in response to chewing gum (max 12 bpm and 0.3°C) in 12 subjects. Gross behavioral indices of working memory such as numerical or character digit span in 8 subjects, or simple visual-motor performance such as reaction speed or accuracy in a two choice scenario in 8 subjects were not affected by betel quid intoxication. Betel quid intoxication strongly influenced the psychological aspects of perception such as slowing of the prospective perception of passage of a 1 minute time interval in 8 subjects (P<0.05) and perceived increased arousal (P<0.01) and perceived decreased ability to think (P<0.05) in 31 subjects. The EEG spectral profile recorded from mental states associated with open and closed eyes, and mental tasks such as reading and eyes closed mental arithmetic were significantly modified (P<0.05) relative to chewing gum by betel quid intoxication in 10 subjects. The prevalence of betel quid consumption across a range of social and work settings warrants greater investigation of this widespread but largely under researched drug.     

iRNA-Methyl: Identifying N-methyladenosine sites using pseudo nucleotide composition

Occurring at adenine (A) with the consensus motif GAC, N⁶-methyladenosine (m⁶A) is one of the most abundant modifications in RNA, which plays very important roles in many biological processes. The nonuniform distribution of m⁶A sites across the genome implies that, for better understanding the regulatory mechanism of m⁶A, it is indispensable to characterize its sites in a genome-wide scope. Although a series of experimental technologies have been developed in this regard, they are both time-consuming and expensive. With the avalanche of RNA sequences generated in the postgenomic age, it is highly desired to develop computational methods to timely identify their m⁶A sites. In view of this, a predictor called “iRNA-Methyl” is proposed by formulating RNA sequences with the “pseudo dinucleotide composition” into which three RNA physiochemical properties were incorporated. Rigorous cross-validation tests have indicated that iRNA-Methyl holds very high potential to become a useful tool for genome analysis. For the convenience of most experimental scientists, a web-server for iRNA-Methyl has been established at http://lin.uestc.edu.cn/server/iRNA-Methyl by which users can easily get their desired results without needing to go through the mathematical details.     

Cellular fatty acid composition of Oerskovia species,CDC Coryneform groups A-3, A-4, A-5, Corynebacterium aquaticum,Listeria denitrificans and Brevibacterium acetylicum

Twenty four strains representing eight species of gram positive yellow-pigmented rods (Oerskovia turbata, Oerskovia xanthineolytica, CDC Coryneform groups A-3, A-4, A-5, Listeria denitrificans, Corynebacterium aquaticum and Brevibacterium acetylicum) were divided into two major groups based on the relative amounts of 12 methyltetradecanoate (15:0^a) obtained by capillary gas liquid chromatography. O. turbata, O. xanthineolytica, CDC groups A-3 and A-4, L. denitrificans and C. aquaticum were placed in the first group due to the presence of a higher percentage (29–47%) of 15:0^a, than CDC group A-5 and B. acetylicum. The latter contained 2–6% of this fatty acid, and were placed in the second group.All species in the two groups except C. aquaticum and CDC group A-4, were further separated from each other based on the qualitative and quantitative differences in their fatty acid compositions. In addition, the eight strains of CDC group A-5 revealed four different patterns and were further divided into four subgroups. This study supports the importance of the composition of cellular fatty acids in differentiating some closely related organisms.     

Genetic Insights into Sporadic Parkinson's Disease Pathogenesis

Intensive research over the last 15 years has led to the identification of several autosomal recessive and dominant genes that cause familial Parkinson’s disease (PD). Importantly, the functional characterization of these genes has shed considerable insights into the molecular mechanisms underlying the etiology and pathogenesis of PD. Collectively; these studies implicate aberrant protein and mitochondrial homeostasis as key contributors to the development of PD, with oxidative stress likely acting as an important nexus between the two pathogenic events. Interestingly, recent genome-wide association studies (GWAS) have revealed variations in at least two of the identified familial PD genes (i.e. α-synuclein and LRRK2) as significant risk factors for the development of sporadic PD. At the same time, the studies also uncovered variability in novel alleles that is associated with increased risk for the disease. Additionally, in-silico meta-analyses of GWAS data have allowed major steps into the investigation of the roles of gene-gene and gene-environment interactions in sporadic PD. The emergent picture from the progress made thus far is that the etiology of sporadic PD is multi-factorial and presumably involves a complex interplay between a multitude of gene networks and the environment. Nonetheless, the biochemical pathways underlying familial and sporadic forms of PD are likely to be shared.     

A therapeutic trial of bezafibrate on patients with hyperlipidemia with or without diabetes mellitus

Bezalip (bezafibrate), at an oral dosage of 200 mg three times a day, has been used on 12 patients with idiopathic hyperlipidemia, and on 12 patients with hyperlipidemia superimposed with diabetes mellitus. Each patient received bezafibrate for 3 months and placebo for 3 months. Blood glycosylated hemoglobin (HbA1) and fasting plasma glucose (FPG) were used as indices of diabetic control. Serum triglyceride (TG), total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C), and TC/HDL-C ratio were measured and calculated in order to compare the antilipemic effects of bezafibrate with that of placebo. Non-parametric Wilcoxon test was used for statistical analysis. In both the idiopathic group and diabetic group, bezafibrate significantly lowered the serum levels of TG and TC/HDL-C, as well as elevated the level of HDL-C. The serum TC levels were not significantly altered in either of the groups. These effects could not be ascribed to an improved diabetic control, since the percent changes of HbA1 were not different between the bezafibrate periods and the placebo periods. There were no significant facial flushing, nor other side effects during the treatment with bezafibrate. It is concluded that bezafibrate has antilipemic effects, and may be helpful in reducing the atherogenic risks.     

The major site of guinea-pig myelin basic protein encephalitogenic in Lewis rats.

In the Lewis rat, fragment 43–88 of the highly encephalitogenic guinea-pig basic protein has been previously shown to retain the full activity of the parent protein. In the present studies this fragment was subjected to controlled chymotryptic digestion so that cleavage occurred only at tyrosine 67, generating two peptides, residues 43-67 and residues 68-88. When compared on an equimolar basis peptide 68-88 had the same encephalitogenic activity as the intact fragment and induced the same degree of immunologically specific cell response as measured by the in vitro lymphocyte stimulation test. Peptide 68-88 was further fragmented by selective tryptic cleavage at arginine 78 after blocking lysine 73 with citraconic anhydride. The two peptides, residues 68-78 and residues 79-88, were not encephalitogenic, indicating that residues adjacent to the point of cleavage contribute to the active site.     

Photodegradation of Dialkyl 1,3-Dithiolan-2-ylidenemalonates and Some Other Pesticides on Solid Particles

On irradiation with UV light the fungicide isoprothiolane (diisopropyl 1,3-dithiolan-2-ylidenemalonate) decomposed rapidly on the silica gel surface. The degradation pathways involved dithiolane ring cleavage, ester hydrolysis, decarboxylation, heterocycles formation such as dithietane and trithiolane, and sulfur liberation. The photoproducts confirmed were oxalic acid, dithiolanylidenemalonic acid, dithiolanylideneacetic acid, 2,4-bis[bis(isopropoxycar-bonyl)methylene]-1, 3-dithietane, 3, 5-bis[bis(isopropoxy-carbonyl)methylene]-1,2,4-trithiolane and sulfur. The methyl and ethyl homologs of isoprothiolane similarly gave the corresponding photoproducts. The surface area where isoprothiolane was placed appeared to be related closely with the photolysis rate. Isoprothiolane decomposed much more rapidly on sand than on a glass plate. This surface effect was greatly depressed under nitrogen atmosphere. Similar phenomena were observed with some other pesticides, with particularly those containing sulfur atoms in the molecule.     

Predicting cleavability of peptide sequences by HIV protease via correlation-angle approach

In designing HIV protease inhibitors as potential drugs for AIDS therapy, knowledge about what peptide sequences in polyproteins are cleavable by HIV proteases is very useful. In this article, based on the formulation that any octapeptide can be uniquely expressed as a 160-dimensional vector and the principle that the similarity of any two such vectors is associated with their correlation angle, a new method is proposed to predict the cleavability of a peptide sequence by HIV-1 and HIV-2 proteases. The average predicted accuracy the new method for the 105 peptide sequences whose cleavability by HIV-1 protease is known is 96/105=9.14%, which is about 8% higher than that by the existing method for the same set of data. A considerably high rate of correct prediction was also obtained when the new method was used to predict the HIV-2 protease-cleaved sites in some proteins.