Functional absence of brain photoreceptors mediating entrainment of circadian rhythms in the adult rat

Summary The photic energy penetrating into the brain was increased in adult rats sustaining craniotomies sealed with transparent plastic. After blinding, these animals failed to entrain their circadian food intake rhythm to light-dark cycles. Short pulses of light did not phase-shift the freerunning rhythm. We conclude that adult rats lack brain photoreceptors mediating entrainment of circadian rhythms.     

Pitch discrimination in the minnow(Phoxinus laevis) at different temperature levels

Zusammenfassung Aus früheren Untersuchungen war bekannt, dass die Elritze (Phoxinus laevis) imstande ist, Töne nach ihrer Frequenz (Tonhöhe) zu unterscheiden, jedoch nur im Frequenzgebiet bis zu etwa 1260 Hz, nicht darüber (die obere Hörgrenze liegt bei etwa 5000 Hz). Es wurde geprüft, welchen Einfluss Wechsel der Temperatur auf die Lage dieser oberen Schwelle der Frequenzunterscheidung hat. Sie lag für die einzelnen Versuchstiere bei 16°C zwischen 800 und 1260 Hz; bei 25°C zwischen 1260 und 1420 Hz, also höher. Der Unterschied beruht nicht auf grösserer Lebhaftigkeit oder Reaktionsbereitschaft der Fische bei der höheren Temperatur. Das Ergebnis steht im Einklang mit der Vermutung, dass die Tonfrequenzunterscheidung bei Fischen nach dem «volley principle» (Wever) erfolgt.     

The effects of the ‘calcium-antagonist’, prenylamine,on the action potential of crayfish muscle (Oronectes virilis)

Zusammenfassung Der organische Ca⁺⁺-Antagonist Prenylamin blockiert die leicht reversiblen Ca⁺⁺-Aktions-potentiale in der Muskelfaser des FlusskrebsesOronectes virilis. Etwas niedrigere Konzentrationen erhöhen die Schwelle und verlängern die Dauer, während schwache Konzentrationen von Prenylamin nur wirksam waren, wenn dieses verwendet wurde, bevor der Muskel dem Aktionspotentialerreger Procain oder Sr⁺⁺ ausgesetzt war.     

Myosin IXB variant increases the risk of celiac disease and points toward a primary intestinal barrier defect

Celiac disease is probably the best-understood immune-related disorder. The disease presents in the small intestine and results from the interplay between multiple genes and gluten, the triggering environmental factor. Although HLA class II genes explain 40% of the heritable risk, non-HLA genes accounting for most of the familial clustering have not yet been identified. Here we report significant and replicable association (P = 2.1 x 10(-6)) to a common variant located in intron 28 of the gene myosin IXB (MYO9B), which encodes an unconventional myosin molecule that has a role in actin remodeling of epithelial enterocytes. Individuals homozygous with respect to the at-risk allele have a 2.3-times higher risk of celiac disease (P = 1.55 x 10(-5)). This result is suggestive of a primary impairment of the intestinal barrier in the etiology of celiac disease, which may explain why immunogenic gluten peptides are able to pass through the epithelial barrier.     

Identification of a new gene mutated in Fraser syndrome and mouse myelencephalic blebs

Fraser syndrome is a recessive, multisystem disorder presenting with cryptophthalmos, syndactyly and renal defects and associated with loss-of-function mutations of the extracellular matrix protein FRAS1. Fras1 mutant mice have a blebbed phenotype characterized by intrauterine epithelial fragility generating serous and, later, hemorrhagic blisters. The myelencephalic blebs (my) strain has a similar phenotype. We mapped my to Frem2, a gene related to Fras1 and Frem1, and showed that a Frem2 gene-trap mutation was allelic to my. Expression of Frem2 in adult kidneys correlated with cyst formation in my homozygotes, indicating that the gene is required for maintaining the differentiated state of renal epithelia. Two individuals with Fraser syndrome were homozygous with respect to the same missense mutation of FREM2, confirming genetic heterogeneity. This is the only missense mutation reported in any blebbing mutant or individual with Fraser syndrome, suggesting that calcium binding in the CALXbeta-cadherin motif is important for normal functioning of FREM2.     

Enhancement of cellular memory by reducing stochastic transitions

On induction of cell differentiation, distinct cell phenotypes are encoded by complex genetic networks. These networks can prevent the reversion of established phenotypes even in the presence of significant fluctuations. Here we explore the key parameters that determine the stability of cellular memory by using the yeast galactose-signalling network as a model system. This network contains multiple nested feedback loops. Of the two positive feedback loops, only the loop mediated by the cytoplasmic signal transducer Gal3p is able to generate two stable expression states with a persistent memory of previous galactose consumption states. The parallel loop mediated by the galactose transporter Gal2p only increases the expression difference between the two states. A negative feedback through the inhibitor Gal80p reduces the strength of the core positive feedback. Despite this, a constitutive increase in the Gal80p concentration tunes the system from having destabilized memory to having persistent memory. A model reveals that fluctuations are trapped more efficiently at higher Gal80p concentrations. Indeed, the rate at which single cells randomly switch back and forth between expression states was reduced. These observations provide a quantitative understanding of the stability and reversibility of cellular differentiation states.