A scenario-based approach to modeling development: a prototype model of C. elegans vulval fate specification

Studies of developmental biology are often facilitated by diagram “models” that summarize the current understanding of underlying mechanisms. The increasing complexity of our understanding of development necessitates computational models that can extend these representations to include their dynamic behavior. Here we present a prototype model of Caenorhabditis elegans vulval precursor cell fate specification that represents many processes crucial for this developmental event but that are hard to integrate using other modeling methodologies. We demonstrate the integrative capabilities of our methodology by comprehensively incorporating the contents of three seminal papers, showing that this methodology can lead to comprehensive models of developmental biology. The prototype computational model was built and is run using a language (Live Sequence Charts) and tool (the Play-Engine) that facilitate the same conceptual processes biologists use to construct and probe diagram-type models. We demonstrate that this modeling approach permits rigorous tests of mutual consistency between experimental data and mechanistic hypotheses and can identify specific conflicting results, providing a useful approach to probe developmental systems.     

Salt-dependent regulation of a CNG channel subfamily in Arabidopsis

Background  

In Arabidopsis thaliana, the family of cyclic nucleotide-gated channels (CNGCs) is composed of 20 members. Previous studies indicate that plant CNGCs are involved in the control of growth processes and responses to abiotic and biotic stresses. According to their proposed function as cation entry pathways these channels contribute to cellular cation homeostasis, including calcium and sodium, as well as to stress-related signal transduction. Here, we studied the expression patterns and regulation of CNGC19 and CNGC20, which constitute one of the five CNGC subfamilies.     

2-Aminobenzimidazoles as potent ITK antagonists: trans-stilbene-like moieties targeting the kinase specificity pocket

Based on the information from molecular modeling and X-ray crystal structures, the kinase specificity pocket of ITK could be occupied upon extension of the right-hand-side of the 2-benzimidazole core of the inhibitors. 2-Aminobenzimidazoles with a trans-stilbene-like extension were designed and synthesized as novel ITK antagonists. Significant improvement on binding affinity and cellular activity were obtained through the trans-stilbene-like antagonists. Several compounds showed inhibitory activity in an IL-2 functional assay.     

A large-scale survey of genetic copy number variations among Han Chinese residing in Taiwan

Background

Winter migration of immature brown trout (Salmo trutta) into freshwater rivers has been hypothesized to result from physiologically stressful combinations of high salinity and low temperature in the sea.

Results

We sampled brown trout from two Danish populations entering different saline conditions and quantified expression of the hsp70 and Na/K-ATPases α 1b genes following acclimation to freshwater and full-strength seawater at 2°C and 10°C. An interaction effect of low temperature and high salinity on expression of both hsp70 and Na/K-ATPase α 1b was found in trout from the river entering high saline conditions, while a temperature independent up-regulation of both genes in full-strength seawater was found for trout entering marine conditions with lower salinities.

Conclusion

Overall our results support the hypothesis that physiologically stressful conditions in the sea drive sea-run brown trout into freshwater rivers in winter. However, our results also demonstrate intra-specific differences in expression of important stress and osmoregulative genes most likely reflecting adaptive differences between trout populations on a regional scale, thus strongly suggesting local adaptations driven by the local marine environment.     

In situ measurements of enzyme activities in the brain

Summary The present review focusses on enzymes involved in the metabolism of amino acid neurotransmitters and the microphotometric determinations of their activities in various layers of the rat hippocampus. The enzymes are NAD-linked isocitrate dehydrogenase (NAD-ICDH), glutamate dehydrogenase (GDH), and GABA transaminase (GABAT), all of which are localized in mitochondria. GDH seems to be restricted to astrocytes, whereas NAD-ICDH and GABAT are localized in neurons as well as in astrocytes. NAD-ICDH is an important enzyme of the tricarboxylic acid cycle and may deliver -ketoglutarate for the formation of glutamate and GABA, which serve as neurotransmitters in the hippocampus. GDH catalyses the interconversion of -ketoglutarate and glutamate, whereas GABAT is the important GABA-degrading enzyme and requires -ketoglutarate for its activity. While differing in their cellular distribution and activity levels, NAD-ICDH, GDH and GABAT are significantly correlated in their hippocampal distribution. Furthermore, developmental and pharmacohistochemical studies suggest that the distribution and activity of astrocytic GDH is correlated with amino-acidergic neurotransmission in the hippocampus. The data reported give further evidence for a metabolic relationship between neurons and astrocytes in the turnover and metabolism of glutamate and GABA.     

Aminopeptidase A is angiotensinase A

Summary Quantitative histochemical measurements of aminopeptidase A (APA; E.C.3.4.11.7) were done kinetically in the kidney glomeruli of rat and mouse with an instrumental setup consisting of a microdensitometer and a computer-supported morphometric system. The histochemical demonstration of APA was carried out using the simultaneous azo coupling technique (purest-grade Fast Blue B as coupling agent and -l-glutamic acid-4-methoxy-2-naphthylamide as substrate). The methodological studies show that APA activity is calcium-ion-dependent and increases linearly with the thickness of the tissue section (3–12 m) and that the time-course of APA activity as determined by linear regression is linear only for the first 1 to 2 min of the reaction. — Kinetic measurements indicate a 40% decrease in APA activities when -l-glutamic acid-4-methoxy-2-naphthylamide (-l-Glu-MNA) is replaced by -l-aspartic acid-4-methoxy-2-naphthylamide. When -l-Glu-MNA is replaced with l-alanine-4-methoxy-2-naphthylamide, which is a substrate of aminopeptidase M (APM) only very low reaction rates are measurable (about 1.4% of those with -l-Glu-MNA). 100 and 130 mM NaCl in the incubation medium increase APA activities by approximately 16%–17%. — To clarify the functional importance of APA in the kidney, their activities were measured under the influence of angiotensins. The glomerulus was selected as the measuring site, for besides APA it contains no APM or other peptidases that could degrade angiotensins (the glomerular dipeptidyl peptidase IV is not inhibited by angiotensin II). Using the Lineweaver-Burk plot, we determined a K _m of 0.16 mM for the APA in rat glomeruli and 0.14 mM in mouse glomeruli. The V _max in mouse glomeruli is 1.6 times higher than in rat glomeruli. Ang iotensin I, II and III competitively inhibit APA in the rat and mouse glomeruli. — With quantitative histochemical techniques it was possible to show that APA is equivalent to angiotensinase A (splitting off the N-terminal aspartic acid from angiotensin I and II).Supported by the Deutsche Forschungsgemeinschaft (SFB 105)     

Zur Histochemie der Flimmerzellen der menschlichen Endosalpinx

Zusammenfassung Die Flimmerzellen des menschlichen Eileiterepithels sind keine einheitliche Population. Zu unterscheiden sind mitochondrienprominente und normale Zellen. In Gewebekulturen wird das Verhalten der Flimmerzellen bei Zugaben verschiedener Hormone und Hormonkombinationen untersucht. Es werden färberisch-lichtmikroskopische (H.E., Semidünnschnitte) und histochemische Methoden verwendet (PAS, Alcianblau, SDH, LDH, ATPase, 5-Nucleotidase, sP, aP). Die auch in vivo beobachteten mitochondrienprominenten Flimmerzellen treten in vitro hauptsäuchlich unter dem Einfluß von Steroidhormonen auf. In hormonfreien Medien, mit zeitlicher Verzögerung auch in hormonhaltigen Medien, schnüren die Flimmerzellen ihre Apices ab. Einige Befunde weisen auf einen möglichen Übergang von Zellen mit Kinocilien in Sekretzellen hin.

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The histochemistry of human endosalpingeal ciliated cells

Summary The human endosalpingeal ciliated cells are not a homogeneous cell population. They can be distinguished into mitochondria prominent and normal cells. The morphological appearance of ciliated cells was studied in organ culture using different hormones and hormone combinations in the culture media. Histological (HE, semithin sections) and histochemical methods (PAS, Alcian Blue, SDH, LDH, ATPase, 5-Nucleotidase, acid and alkaline Phosphatase) were applied. Those mitochondria prominent ciliated cells which are seen in the native endosalpinx can in vitro also be determined mainly under the influence of steroid hormones (hydrocortisone and progesterone). In hormone free incubation media the apices of ciliated cells are separated. This will happen in hormone containing media, too, but with delay, however. Some results are in agreement with the possible transformation from ciliated cells to secretory cells.

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Die Untersuchung wurde im Anatomischen Institut der Universität Regensburg (Lehrstuhl: Prof. Dr.Dr. K.-H. Wrobel) durchgeführt     

Zum Problem der Dipterenblumen

Zusammenfassung Wenn wir die obigen Ausführungen überDipteren- oder Fliegenblumen nochmals überblicken, so müssen wir feststellen, daß nur bei den Aasblumen direkte Wechselbeziehungen zwischen diesen und einer bestimmten Bestäubergruppe nachzuweisen sind. Von all den als mehr oder weniger charakteristisch angegebenen Eigenschaften der Aasblumen konnte bisher nur der Geruch in eine direkte Beziehung zur Bestäubung gebracht werden, indem er koprophile Insekten, d. h. Aasfliegen und Aaskäfer, anlockt. Dipteren besuchen aber einen viel größeren Kreis von Blumen. Dabei handelt es sich in Übereinstimmung mit ihrem meist plumpen Saugrüssel um Blüten mit mehr oder minder offen liegendem Nektar, besonders solche mit lebhaft glänzenden Nektarien (Glanzwirkung). Hinsichtlich der Farben herrschen Gelb, Grün und Weiß vor, was dem Farbensinn der Tiere entspricht. Häufig entströmt den Blüten ein an Aminen reicher Geruch, der den Besuch durchMusciden, Tachiniden und andere begünstigt, den durchApiden in einigen Fällen mehr oder weniger einschränkt. Es handelt sich dabei gewissermaßen um Übergänge zu den Aasblumen. Im allgemeinen liegen aber keine so engen Wechselbeziehungen zwischen diesen Blumen und Fliegen vor, daß von Anpassungen gesprochen werden könnte. Wenn bei manchen Formen, denen kein nennenswerter Geruch entströmt, unter den Besuchern Fliegen überwiegen, so liegt der Grund dafür weniger im Bau und den Lebenserscheinungen der betreffenden Blüten, als vielmehr im Biotop begründet, der sehr reich anDipteren, arm aber anApiden ist, denen die hohe Bodenfeuchtigkeit derartiger Standorte nicht zusagt.Die vorliegende Untersuchung zeigt, wie problematisch es ist, ein blütenökologisches System der Insektenblumen nur auf den verschiedenen Bestäubergruppen aufbauen zu wollen.     

Histological and histochemical studies on testis, epididymis and ductus defrens of the rooster (Gallus domesticus)]

Testis, epididymis and ductus deferens of the adult domestic fowl and male gonads of juvenile roosters have been studied by means of histochemical and histological methods. Testicular interstitial cells: According to enzyme-histochemical results oxidative energy production seems to be of minor importance. An extraordinarily high activity of lysosomal enzymes (acid phosphatase and esterases in the adult, esterases only in the immature) is observed. Positive reactions of 3beta-steroid-dehydrogenase and enzymes of the pentose phosphate cycle indicate steroid hormone production; the pathways of the steroid synthesis, however, are probably different in adult and immature testes. A remarkable LAP content of juvenile Leydig cells is a parameter of an increased protein metabolism. Areas of reserve cells: Focal accumulation of these cell types are observed in testis and epididymis of the immature and in the epididymis of the adult fowl. Reserve cells reveal distinct activities of LAP (prospective growth ability) and 3beta-HstDH (reserve capacity for steriod synthesis). All other enzymes studied react weakly, thus pointing to a generally low metabolic activity. Seminiferous tubules: The strong reaction of alkaline phosphatase in the peritubular cells may play a part in energy disposition for contractions. Sertoli cells of adult animals are rich in lysosomal enzymes and enzymes of the glycolytic chain but oxidoreductases react weaker than in mammalian Sertoli cells. This indicates that nutritive interactions between germ and Sertoli cells in birds are different from those in mammals: The basally orientated germ cells of birds contain strong activities of diaphorases, LDH, SDH, Cyto-Ox and seem to be metabolically rather indipendent from Sertoli cells.