Activin A affects feeding by promoting the inner diameter and muscle development of the pharynx and oesophagus in zebrafish (Danio rerio) larvae

Activin A belongs to the superfamily of transforming growth factor-β and plays an important role in hormone regulation and tissue development. However, few research studies have been conducted on the effect of activin A on feeding organs in fish. In this study, the zebrafish (Danio rerio) larvae were treated with 1 ng ml^–1 activin A for 8 days continuously. The haematoxylin and eosin (H&E) staining section results revealed that the transverse inner diameter of the pharynx and oesophagus significantly increased on the third and eighth days after treatment compared with the control group (P < 0.05). On the eighth day, the cross-sectional area of the pharyngeal muscle increased by 8638 μm² compared to the control group (P < 0.05). The RNA in situ hybridization results also showed that the expression of skeletal muscle-specific genes (myog and myod) was significantly increased in pharyngeal muscle on the eighth day. Furthermore, the qRT-PCR results showed the expression of gh gene was significantly increased on the eighth day (P < 0.05). At the same time, more larvae in activin A group were able to feed larger brine shrimp (Artemia) than in the control group on the eighth day. In conclusion, activin A could affect feeding by promoting the inner diameter and muscle development of the pharynx and oesophagus in zebrafish larvae. This study is the first to report that the development of the pharynx and oesophagus can directly affect food intake in fish larvae, which provides a theoretical basis for the study of food intake of fish at an early stage.     

Computational prediction and experimental validation of the activator function of C2-β-D-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone on pancreatic and hepatic hexokinase

Abstract

This study identifies and validates hexokinase type 4 (HK4), an isozyme of hexokinase in the liver and pancreas, as an important target of C2-β-D-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone (βdGT), a xanthone glucoside suggested to have antidiabetic property. In the study, we applied the computational pipeline of molecular docking followed by the molecular dynamics simulations to shortlist potential βdGT protein targets. The analysis of protein dynamics and the binding free energy (ΔG) led us to the identification of HK4 as a key βdGT target, whereby the binding mode and domain dynamics suggested the activator function of βdGT. βdGT bound to the allosteric site of the isozyme ～13?Å away from the substrate (glucose)-binding site. The binding free energy of the ligand-protein complex was energetically feasible (ΔG, –41.61?kcal/mol) and the cleft angle deviation between the two (small and large) domains of HK4 revealed differential HK4 dynamics in response to βdGT binding. 3D structure analysis of the isozyme-ligand complex highlighted the role of Arg63, Glu67 and Lys458 in ligand stabilization and hydrophobic interactions mediated by Tyr214 and Met235. Experimental validation of the results of computational analysis confirmed the activator function of βdGT on HK4. The study has implication in diabetes as βdGT may be used to lower the blood glucose level by activating hepatic and pancreatic hexokinase without the risk of hypoglycemia.

Communicated by Ramaswamy H. Sarma     

Reduction of nuclear Y654-p-β-catenin expression through SH3GL2-meditated downregulation of EGFR in chemotolerance TNBC: Clinical and prognostic importance

Triple negative breast cancer (TNBC) originates from a less differentiated ductal cell of breast, which is less sensitive to chemotherapy. The chemotolerance mechanism of TNBC has not yet been studied in detail. For this reason, molecular profiles (expression/genetic/epigenetic) of Y654-p-β-catenin (active) and its kinase epidermal growth factor receptor (EGFR) along with SH3GL2 (regulator of EGFR homeostasis) were compared between neoadjuvant chemotherapy treated (NACT) and pretherapeutic TNBC samples. Reduced nuclear expression of Y654-p-β-catenin protein with low proliferation index and CD44 prevalence showed concordance with reduced expression of EGFR/Y1045-p-EGFR proteins in the NACT samples than the pretherapeutic TNBC samples. Infrequent messenger RNA expression, gene amplification (10–32.5%), and mutation (1%) of EGFR were seen in the TNBC samples irrespective of therapy, suggesting the importance of EGFR protein stabilization in this tumor. The upregulation of SH3GL2 seen in the NACT samples in contrast to the pretherapeutic samples might be due to its promoter hypomethylation, as seen in the quantitative methylation assay. A similar trend of upregulation of SH3GL2 and downregulation of EGFR, Y1045-p-EGFR, Y654-p-β-catenin were seen in the MDA-MB-231 cell line using antharacycline antitumor drugs (doxorubicin/nogalamycin). The NACT patients with reduced expression of Y654-p-β-catenin and/or EGFR and high expression of SH3GL2 showed comparatively better prognosis than the pretherapeutic patients. Thus, our study showed that reduced nuclear expression of Y654-p-β-catenin in NACT samples due to downregulation of EGFR protein through promoter hypomethylation-mediated upregulation of SH3GL2, resulting in low proliferation index/CD44 prevalence with better prognosis of the NACT patients, might have an important role in the chemotolerance of TNBC.     

Interactions of Ralstonia solanacearum and Pectobacterium carotovorum with Meloidogyne incognita on potato

Effect of interactions of Meloidogyne incognita with Ralstonia solanacearum and interaction of M. incognita with Pectobacterium carotovorum were studied in sequential and simultaneous inoculations on potato (Solanum tuberosum). Inoculation of M. incognita caused a lesser reduction in plant growth than caused by R. solanacearum. Inoculation of M. incognita plus R. solanacearum caused a greater reduction in plant growth than the damage caused by either pathogen. Inoculation of M. incognita prior to R. solanacearum resulted in a greater reduction in plant growth than R. solanacearum was inoculated prior to M. incognita. However, inoculation of M. incognita or P. carotovorum caused similar reduction in plant growth. Inoculation of P. carotovorum prior to M. incognita caused lesser reduction in plant growth than simultaneous inoculation of both pathogens. Inoculation of M. incognita caused galling in potato roots but the size of galls was small. Inoculation of P. carotovorum or R. solanacearum with M. incognita had adverse effect on galling and nematode multiplication. Wilting or soft rot index was 3 when R. solanacearum or P. carotovorum was inoculated alone. In other treatments, where R. solanacearum or P. carotovorum was inoculated with M. incognita, wilting or soft rot indices were 5.     

Effect of Tillage and Water Management on the Population Behaviour of Root-Knot Nematodes Meloidogyne Triticoryzae in Rice Crop

The effects of puddling and water regimes on hydraulic conductivity (cm/day) of soil and on bulk density (mg/m 3 ) during rice culture, soil physical characteristics of the experimental field population densities of plant-parasitic nematodes have been studied. Puddling reduced the bulk density of soil and decreased the hydraulic conductivity in the upper layers but not in the deeper layers of soil aeration was reduced due to high moisture levels retained in the puddled soil. Population density of M. triticoryzae declined in puddled soil. The invasion of the roots by the second-generation infective juveniles was reduced. The population density of the root-knot nematodes was higher in the non-puddled soil especially in unsubmerged condition compared to puddled and submerged soil. However, if the seedlings were already infected before transplanting and submergence, the nematode could survive well and reproduce within the aerenchyma of the root.     

Relative Desiccation Survival Potential of Two Root-Knot Nematode Species,Meloidogyne Incognita and M. Triticoryzae and Relationship With Their Habitat and Cuticle Characteristics*

Abstract

Horsfall, J. G. (Ed.): Annual Review of Phytopathology. Vol. 4. VII + 423 S. Palo Alto, 1966: Annual Reviews, Inc. Leinen, 9,00 $. Reviewed by K. Naumann.

Gregory, P. H. und Monteith, J. L. (Ed.): Airborne microbes. Seventeenth Symposium of the Society for General Microbiology held at the Imperial College, London April 1967. XII + 385 S., mit Abb. u. Tab. London, 1967: Cambridge University Press, Leinenrücken, 75 s. Reviewed by H. J. Müller.

Raper, J. R.: Genetics of sexuality in higher fungi. VIII + 283 S., mit Abb. u. Tab., New York, 1966: The Ronald Press Company, Leinen, 12,00 $. Reviewed by M. Schmiedeknecht.

Albrecht, F. O.: Polymorphisme phasaire et biologie des acridiens migrateurs. X + 194 S., 52 Abb. Paris, 1967: Masson et Cie, Éditeurs, karton., 50 F. Reviewed by R. Fritzsche.

Wigglesworth, V. B.: Insect physiology. VII + 134 S., 12 Abb., London, 1966: Methuen &; Co Ltd., brosch., 10 s 6 d. Reviewed by G. Schäller.

Machlis, L. (Ed.): Annual Review of Plant Physiology. Vol. 18. VIII + 480 S., mit Abb. u. Tab., Palo Alto, Ca., 1967: Annual Reviews, Inc., Leinen, 9,00 $. Reviewed by H. Wolffgang.

Newton, B. A. und Reynolds, P. E. (Ed.): Biochemical studie of antimicrobial drugs. (Sixteenth symposium of the Society for General Microbiology held at the Royal Institution, London, April 1966). X + 349 S., mit Abb. u. Tab., London, 1966: Cambridge University Press, Halbleinen, 60 s. Reviewed by H. J. Müller.

Pilet, P.-É.: La cellule, structure et fonctions. 406 S., 310 Abb.; 32 ganzs. Abb., Paris 1966: Schwarz-Weiß-Tafeln. Masson et Cie, Editeurs, brosch. 38 F. Reviewed by K. Schmelzer.

Ciba (Ed.): Dimecron 257 S. Basle, Switzerland, 1967: P.O. Box — CIBA — Kunststoff Reviewed by Horst Beitz.

Bellamy, L. J.: Ultrarot-Spektrum und chemische Konstitution. 2. Auflage, 325 S., 11 Abb., 23 Tab. Darmstadt, 1966: Dr. Dietrich Steinkopff Verlag, kart., 28,— DM Reviewed by Volker Müller.

Bahr, G. F.; Zeitler, E. H. (Ed.): Quantitative electron microscopy. 1965, VIII + 605 (1340) S., mit Abb. u. Tab., Leinen, 16,00 $, Baltimore (Md.), The Williams &; Wilkins Company. Reviewed by H. B. Schmidt.     

Memory T cells are uniquely resistant to melanoma-induced suppression

We have previously observed that in vivo exposure to growing melanoma tumors fundamentally alters activated T cell homeostasis by suppressing the ability of naïve T cells to undergo antigen-driven proliferative expansion. We hypothesized that exposure of T cells in later stages of differentiation to melanoma would have similar suppressive consequences. C57BL/6 mice were inoculated with media or syngeneic B16F10 melanoma tumors 8 or 60 days after infection with lymphocytic choriomeningitis virus (LCMV), and splenic populations of LCMV-specific T cells were quantified using flow cytometry 18 days after tumor inoculation. Inoculation with melanoma on post-infection day 8 potentiated the contraction of previously activated T cells. This enhanced contraction was associated with increased apoptotic susceptibility among T cells from tumor-bearing mice. In contrast, inoculation with melanoma on post-infection day 60 did not affect the ability of previously established memory T cells to maintain themselves in stable numbers. In addition, the ability of previously established memory T cells to respond to LCMV challenge was unaffected by melanoma. Following adoptive transfer into melanoma-bearing mice, tumor-specific memory T cells were significantly more effective at controlling melanoma growth than equivalent numbers of tumor-specific effector T cells. These observations suggest that memory T cells are uniquely resistant to suppressive influences exerted by melanoma on activated T cell homeostasis; these findings may have implications for T cell–based cancer immunotherapy.     

Apolipoprotein E gene polymorphism and the risk of left ventricular dysfunction among Egyptian β-thalassemia major

In Egypt, β-thalassemia is the most common hereditary hemolytic anemia. Cardiac dysfunction, secondary to iron overload with formation of oxygen free radicals, is the most common cause of death in β-thalassemia patients. This study was designed to determine whether the allelic genotype of apolipoprotein E (Apo E), which exhibits antioxidant properties, could represent a genetic risk factor for the development of left ventricular (LV) dysfunction in β-thalassemia major. Fifty Egyptian β-thalassemia major patients were subjected to echocardiography to assess LV function. Apo E genotyping by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) was done for all patients in addition to 50 age and sex matched healthy control subjects. Patients were classified into three groups. Group I and II were clinically asymptomatic. Group II subjects had evidence of LV dilatation, while Group III patients had clinical and echocardiographic findings of LV failure. Apo E4 allele was significantly higher among Group II and III than in controls. In conclusion, Apo E4 allele can be considered as a genetic risk factor for LV dysfunctions in β-thalassemic patients. It could be used as predictive indicator for additional risk of LV failure, particularly in asymptomatic patients with LV dilatation, requiring a closer follow-up, to prevent further disease progression.     

Routes into education and employment for young Pakistani and Bangladeshi women in the UK

The article examines the educational and employment experiences and aspirations of young Pakistani and Bangladeshi people living in Oldham, in Great Manchester. Many young people demonstrated high aspirations and high levels of participation, particularly in relation to the educational and occupational level of their parents. Explanatory factors include the cultural value of education among Asian groups, the desire by parents to ensure success for their children and the ethnic penalty which these young people incur in the labour market. However, not all Pakistani and Bangladeshi young people have these aspirations. Girls who wished to continue their education faced a more complex situation than boys; for girls it was important to avoid jeopardizing the family honour. Nonetheless, national statistics show a marked increase in the numbers of young Pakistani and Bangladeshi women in full-time undergraduate courses in recent years. Women with degree level qualifications showed considerable determination to combine paid employment with family life.