Theoretical and Experimental Studies of Energy Exchange from Jackrabbit Ears and Cylindrically Shaped Appendages

Convection properties of jackrabbit ears were examined in a wind tunnel and in the field in an attempt to study the possible thermal role of the large ears. This work was part of a study on energy exchange of appendages. Cylindrical copper models of various shapes, aluminum castings of domestic and jackrabbit ears, and an amputated jackrabbit ear were studied in a wind tunnel (a) to define the range for convective heat loss for appendages of various shapes, and (b) to study the effect on convection of model shape and orientation to the wind. Shape, i.e. length and closure, proved important. Orientation to the wind produced no consistent or significant variation in the convection coefficient. The convection coefficients from the ear castings fell within the range generated from the cylindrical models. The convection coefficients for the amputated rabbit ear fell partially within the range. Net thermal radiation loss at midday from the jackrabbit ears was found to be small. Convection from the ears, however, could account for the loss of over 100% of the animal's metabolic heat at an air temperature of 30°C. If air temperature exceeds body temperature, the animal must either store heat or resort to the evaporation of water.     

Docking studies on novel analogues of 8 methoxy fluoroquinolones against GyrA mutants of Mycobacterium tuberculosis

Background

Modeling of transmembrane domains (TMDs) requires correct prediction of interfacial residues for in-silico modeling and membrane insertion studies. This implies the defining of a target sequence long enough to contain interfacial residues. However, too long sequences induce artifactual polymorphism: within tested modeling methods, the longer the target sequence, the more variable the secondary structure, as though the procedure were stopped before the end of the calculation (which may in fact be unreachable). Moreover, delimitation of these TMDs can produce variable results with sequence based two-dimensional prediction methods, especially for sequences showing polymorphism. To solve this problem, we developed a new modeling procedure using the PepLook method. We scanned the sequences by modeling peptides from the target sequence with a window of 19 residues.

Results

Using sequences whose NMR-structures are already known (GpA, EphA1 and Erb2-HER2), we first determined that the hydrophobic to hydrophilic accessible surface area ratio (ASAr) was the best criterion for delimiting the TMD sequence. The length of the helical structure and the Impala method further supported the determination of the TMD limits. This method was applied to the IL-2Rβ and IL-2Rγ TMD sequences of Homo sapiens, Rattus norvegicus, Mus musculus and Bos taurus.

Conclusions

We succeeded in reducing the variation in the TMD limits to only 2 residues and in gaining structural information.     

Interpretation of single progesterone measurement in diagnosis of anovulation and defective luteal phase: observations on analysis of the normal range.

Single serum progesterone determinations were made in 79 apparently normal women with a regular menstrual cycle. A normal range (40 subjects) was derived from the concentrations in the follicular phase and used to define an "anovular" range for luteal phase values (nine out of 39 subjects). The remaining luteal phase values were used to construct an "ovular" range for the luteal phase and, within this range, to define a group of values (less than the 20th centile) which could be described as a "defective luteal phase." The cut off limits between ovular and anovular and between normal and defective luteal phases were respectively two and four times the follicular phase median. It is proposed that the numerical findings of this study may be used as a rule of thumb for defining normality and abnormality from a single serum progesterone determination.     

2-Aryl-2-hydroxyethylamine substituted 4-oxo-4,7-dihydrothieno[2,3-b]pyridines as broad-spectrum inhibitors of human herpesvirus polymerases

A novel series of 2-aryl-2-hydroxyethylamine substituted 4-oxo-4,7-dihydrothieno[2,3-b]pyridine-5-carboxamides have been identified as potent antivirals against human herpesviruses. These compounds demonstrate broad-spectrum inhibition of the herpesvirus polymerases HCMV, HSV-1, EBV, and VZV with high specificity compared to human DNA polymerases.     

Local and nonlocal environments around Cis peptides

Although the vast majority of peptide bonds in folded proteins are found in the trans conformation, a small percentage are found in the less energetically favorable cis conformation. Though the mechanism of cis peptide bond formation remains unknown, the role of local aromatics has been emphasized in the literature. This paper presents results from a comprehensive statistical analysis of both the local and nonlocal (i.e., tertiary) environment around cis peptides. In addition to an increased frequency of aromatic residues in the local environment around cis peptides, a number of nonlocal differences in protein secondary and tertiary structure between cis and trans peptides are found: (i) coil regions containing cis peptides are almost twice as long as those without cis peptides and include more Tyr and Pro residues; (ii) cis peptides occur with high frequencies in coil regions near large beta-structures; (iii) there is a nonlocal enrichment of Cys, His, Tyr, and Ser in the tertiary environment surrounding cis peptides when compared to trans peptides; and (iv) on average, cis peptides make fewer medium-range and more long-range contacts than trans peptides do. On the basis of these observations, it is concluded that nonlocal factors play a significant role in cis peptide formation, which has not been fully appreciated previously. An autocatalytic model for cis peptide formation is discussed as are consequences for protein folding.     

Glucose lowering effect of transgenic human insulin-like growth factor-I from rice: <Emphasis Type="Italic">in vitro</Emphasis> and <Emphasis Type="Italic">in vivo</Emphasis>studies

Background  

Human insulin-like growth factor-I (hIGF-I) is a growth factor which is highly resemble to insulin. It is essential for cell proliferation and has been proposed for treatment of various endocrine-associated diseases including growth hormone insensitivity syndrome and diabetes mellitus. In the present study, an efficient plant expression system was developed to produce biologically active recombinant hIGF-I (rhIGF-I) in transgenic rice grains.     

Characterization and mapping of a nonessential pseudorabies virus glycoprotein.

Antigenic variants of pseudorabies virus (PRV) containing mutations in a viral glycoprotein with a molecular weight of 82,000 (gIII) were isolated by selecting for resistance to a complement-dependent neutralizing monoclonal antibody (MCA82-2) directed against gIII. These mutants were completely resistant to neutralization with MCA82-2 in the presence of complement. Two mutants selected for further studies either did not express gIII or expressed an improperly processed form of the glycoprotein. The mutations were also associated with an altered plaque morphology (syncytium formation). The gIII gene was mapped by marker rescue of a gIII- mutant with cloned restriction enzyme fragments to the long unique region of the PRV genome between 0.376 and 0.383 map units. This corresponds to the map location of a glycoprotein described by Robbins et al. (J. Mol. Appl. Gen. 2:485-496, 1984). Since gIII is nonessential for viral replication in cell culture and has several other characteristics in common with the herpes simplex virus glycoprotein gC, gIII may represent the PRV equivalent to herpes simplex virus gC.     

Disease-associated glycosylated molecular variants of human C-reactive protein activate complement-mediated hemolysis of erythrocytes in tuberculosis and Indian visceral leishmaniasis

Human C-reactive protein (CRP), as a mediator of innate immunity, removed damaged cells by activating the classical complement pathway. Previous studies have successfully demonstrated that CRPs are differentially induced as glycosylated molecular variants in certain pathological conditions. Affinity-purified CRPs from two most prevalent diseases in India viz. tuberculosis (TB) and visceral leishmaniasis (VL) have differential glycosylation in their sugar composition and linkages. As anemia is a common manifestation in TB and VL, we assessed the contributory role of glycosylated CRPs to influence hemolysis via CRP-complement-pathway as compared to healthy control subjects. Accordingly, the specific binding of glycosylated CRPs with erythrocytes was established by flow-cytometry and ELISA. Significantly, deglycosylated CRPs showed a 7–8-fold reduced binding with erythrocytes confirming the role of glycosylated moieties. Scatchard analysis revealed striking differences in the apparent binding constants (10⁴–10⁵ M⁻¹) and number of binding sites (10⁶–10⁷sites/erythrocyte) for CRP on patients’ erythrocytes as compared to normal. Western blotting along with immunoprecipitation analysis revealed the presence of distinct molecular determinants on TB and VL erythrocytes specific to disease-associated CRP. Increased fragility, hydrophobicity and decreased rigidity of diseased-erythrocytes upon binding with glycosylated CRP suggested membrane damage. Finally, the erythrocyte-CRP binding was shown to activate the CRP-complement-cascade causing hemolysis, even at physiological concentration of CRP (10 μg/ml). Thus, it may be postulated that CRP have a protective role towards the clearance of damaged-erythrocytes in these two diseases.     

The use of invertebrate functional groups to characterize ecosystem attributes in selected streams and rivers in south Brazil

An analysis conducted at nine stream/river sites in the Atlantic Forest region in the State of Paraná, Brazil used macroinvertebrate functional feeding group (FFG) assessments to evaluate ecological condition of the sites. The FFG approach categorizes qualitative macroinvertebrate collections according to their morphological-behavioral adaptations for food acquisition (e.g. scrapers that harvest non-filamentous, attached algae from stable surfaces in flowing water). FFG ratios were employed as surrogates for stream/river ecosystem attributes: balance between autotrophy and heterotrophy; linkage between riparian inputs of coarse particulate organic matter and in-stream food webs; relative dominance of fine particulate organic matter in transport (suspended load) compared to that deposited in the sediments; and geomorphic stability of the channel. The analyses indicated that all nine sites were heterotrophic, six of the nine carried expected levels of suspended organic load and showed below expected linkage with riparian inputs, and in only two were stable substrates limiting. The implications of the findings and recommendations for further analysis and modifications of the protocol are discussed.