Seasonal changes in the hypothalamo-hypophyseal-ovarian system in the catfish,Heteropneustes fossilis (Bloch)*

The annual reproductive cycle of the catfish, H. fossilis (Bloch) is divided into the preparatory period (February-April), the prespawning period (May-June), the spawning period (July-August) and the postspawning period (September-January). During the early postspawning period (September-November), the hypothalamo-hypophyseal-ovarian system shows a gradual regression. In January, the hypothalamic nuclei, the pars magnocellularis (PMC), the pars parvocellularis (PPC) of the nucleus preopticus (NPO), and the nucleus lateralis tuberis (NLT) show renewed activity, as shown by a significant increase in their nuclear diameters and an accumulation of neurosecretory material (NSM) in their cell bodies. The hypophysis and the ovary remain quiescent. During the preparatory period, all the hypothalamic neurons studied indicate decreased activity but simultaneously show an accumulation of NSM in their cell bodies. The number of granulated basophils in the proximal pars distalis (PPD) of the hypophysis remains low but ovarian weights increase, presumably due to the multiplication of oogonia. In the prespawning period, there is a marked accumulation of NSM in the cell bodies of the hypothalamic neurons and at the same time the number of granulated basophils in the PPD of the hypophysis dramatically increases with concomitant increase in vitellogenic activity in the ovary. During the spawning period, the hypothalamic neurons continue to store NSM in their cell bodies and simultaneously there is a tremendous increase in the number of granulated basophils in the PPD of the hypophysis and the ovary has a large proportion of yolky primary oocytes. Spawning is associated with a significant degranulation of the granulated basophils in the PPD of the hypophysis. The significance of the results is discussed in relation to the environmental and hormonal regulation of seasonal ovarian activity.     

Immune regulation of complement components in vivo

Immune regulation of individual complement components has been studied in F₁ hybrids obtained from mating normal males with females homozygous for a genetically controlled deficiency of those components. Experiments have been performed with C5-deficient mice, C6-deficient rabbits, and C4-deficient guinea pigs. Prior to mating, complement-deficient females were rendered hyperimmune to the component they lacked and their F₁ offspring were treated postnatally with antibody to the pertinent complement component. We had previously shown that antibody treatment could suppress C5 production in mice but in experiments presented here, similar antibody treatment had no effect on in vivo biosynthesis of C6 in rabbits and C4 in guinea pigs. Variation in the susceptibility of these three components of complement to regulation by antibody might reflect differences in the inducing antibody, the ontogeny of the complement component, the sites of origin, or the genetic mechanisms responsible for the deficiency states. Lack of the ability to suppress with antibody in vivo does not denote an inability to suppress with antibody in analogous in vitro systems.     

Optical activity of saccharides—the vacuum-uv origin of sodium-D rotation

A semiempirical theory of saccharide optical activity indicates that the dominant source of Na_D rotation is a vacuum-uv CD band near 150 nm, a band observed experimentally in polysaccharide film CD spectra. The model is a modification of polarizability theory in which high-energy electronic excitations are coupled by degenerate perturbation theory, giving rise to “molecular excitons.” The existence of an excitation mode well separated in energy from even higher energy modes arises from the local symmetry of tetrahedral carbon atoms in a puckered ring structure. Calculated Na_D rotations correlate well with experimental values.     

In vitro activity of the human neutrophil cathepsin G on Eimeria tenella sporozoites

The role of human neutrophil cathepsin G (Cat G) on Eimeria tenella sporozoites was studied in vitro. Sporozoites were incubated for 2 hr at 37 C in PO4 buffer, 0.9% NaCl (PBS), pH 7.6 in the presence of Cat G (50 micrograms/ml), diisopropyl fluorophosphate-inhibited Cat G (DFP-Cat G) (50 micrograms/ml) or PBS alone, prior to being inoculated into embryonated eggs. As judged by oocyst production on day 7 postinoculation, embryo mortality and the hemorrhage scores, both Cat G and DFP-Cat G demonstrated anticoccidial activity; greater activity was obtained with the DFP-Cat G. Sporozoites were exposed also to increasing concentrations of native and trypsin-digested DFP-Cat G (0-100 micrograms/ml) under the same conditions. Significant protection (37% and 49% for native and digested DFP-Cat G, respectively) was obtained with a low concentration (5 mu/ml), and higher concentrations resulted in 70% and 84% protection, respectively. The primary bactericidal domain of Cat G, the HPQYNQR peptide, at 3 concentrations (25, 50, and 100 micrograms/ml), reduced the oocyst production by 46%, 16%, and 15%, respectively. The anticoccidial activity of Cat G may involve a peptide fragment different from the antimicrobial domain of the enzyme.     

Machine learning-based investigation of the cancer protein secretory pathway

Deregulation of the protein secretory pathway (PSP) is linked to many hallmarks of cancer, such as promoting tissue invasion and modulating cell-cell signaling. The collection of secreted proteins processed by the PSP, known as the secretome, is often studied due to its potential as a reservoir of tumor biomarkers. However, there has been less focus on the protein components of the secretory machinery itself. We therefore investigated the expression changes in secretory pathway components across many different cancer types. Specifically, we implemented a dual approach involving differential expression analysis and machine learning to identify PSP genes whose expression was associated with key tumor characteristics: mutation of p53, cancer status, and tumor stage. Eight different machine learning algorithms were included in the analysis to enable comparison between methods and to focus on signals that were robust to algorithm type. The machine learning approach was validated by identifying PSP genes known to be regulated by p53, and even outperformed the differential expression analysis approach. Among the different analysis methods and cancer types, the kinesin family members KIF20A and KIF23 were consistently among the top genes associated with malignant transformation or tumor stage. However, unlike most cancer types which exhibited elevated KIF20A expression that remained relatively constant across tumor stages, renal carcinomas displayed a more gradual increase that continued with increasing disease severity. Collectively, our study demonstrates the complementary nature of a combined differential expression and machine learning approach for analyzing gene expression data, and highlights key PSP components relevant to features of tumor pathophysiology that may constitute potential therapeutic targets.     

On chip optofluidic low-pressure monitoring device

We present an on chip optofluidic surface deformable liquid Dove prism (LDP) based low-fluid flow pressure monitoring device. The unique design of the device in combination with liquid and soft solid enabled by the total internal reflection of light makes the sensor highly sensitive and compatible with the integration of a microfluidic and/or Lab-on-a-chip device. A layer-by-layer soft lithographic (LSL) and 3D printing technique are exploited to make the device. We have used Polydimethylsiloxane (PDMS) as the layer material and two variety of liquids (a) immersion oil (IO) and (b) di-iodomethane (DI) as refracting medium to construct the LDP sensor. Optical ray tracing simulation is performed to optimize the sensor. The pressure sensor shows sensitivity as high as ±28.5 mV per 50 Pa pressure with an error ± 2.5 mV and repeatability of ~99.56% at full scale. We have shown the applicability of the sensor by capturing and analyzing respiratory pressure signals of some human subjects at numerous conditions.     

Homepeptide Repeats:Implications for Protein Structure,Function and Evolution

Analysis of protein sequences from Mycobacterium tuberculosis H37Rv(Mtb H37Rv) was performed to identify homopeptide repeatcontaining proteins(HRCPs).Functional annotation of the HRCPs showed that they are preferentially involved in cellular metabolism.Furthermore,these homopeptide repeats might play some specific roles in protein-protein interaction.Repeat length differences among Bacteria,Archaea and Eukaryotes were calculated in order to identify the conservation of the repeats in these divergent kingdoms.From the results,it was evident that these repeats have a higher degree of conservation in Bacteria and Archaea than in Eukaryotes.In addition,there seems to be a direct correlation between the repeat length difference and the degree of divergence between the species.Our study supports the hypothesis that the presence of homopeptide repeats influences the rate of evolution of the protein sequences in which they are embedded.Thus,homopeptide repeat may have structural,functional and evolutionary implications on proteins.     

Phosphorylation of multifunctional nucleolar protein nucleophosmin (NPM1) by aurora kinase B is critical for mitotic progression

The functional association of NPM1 with Aurora kinases is well documented. Surprisingly, although NPM1 is a well characterized phosphoprotein, it is unknown whether it is a substrate of Aurora kinases. We have found that Aurora kinases A and B can phosphorylate NPM1 at a single serine residue, Ser125, in vitro and in vivo. Phosphorylated-S125-NPM1 (pS125-NPM1) localizes to the midbody region during late cytokinesis where it colocalizes with Aurora B. The overexpression of mutant (S125A) NPM1 resulted in the deregulation of centrosome duplication and mitotic defects possibly due to cytokinesis failure. These data suggest that Aurora kinase B-mediated phosphorylation of NPM1 plays a critical role during mitosis, which could have wider implications in oncogenesis.