"Rapid regeneration" in the cat retina: a case for spreading depression

Fundus reflectometry of the cat retina showed that under certain circumstances a rapid increase in density may follow intense bleaching exposures. The spectral characteristics of the density changes indicated that neither rhodopsin nor its bleach products could be responsible for this effect. The poor condition of the animals in which the phenomenon was observed and its conspicuous absence in the majority of the experimental runs suggested that the effect was associated with a process other than the resynthesis of rhodopsin. It was shown that an extrareceptoral event, spreading depression (SD) of the retina, is the most likely source of the rapid spectral change. The well-known tissue alterations associated with SD were induced in the retina independently of pigment density change. The resultant difference spectra resembled those produced when the rapid density increase occurred spontaneously. It seems likely that the abnormal physiological condition of those cats in which the phenomenon is more frequently observed primes the retina for the light-induced generation of spreading depression.     

Determining the ‘health’ of estuaries: Priorities for ecological research

‘Ecosystem health’ is a relatively new concept for environmental science and management. Although at least two international journals use the term in their titles, there have been few applications of it for estuaries and soft-sediment habitats around the world. In this paper I: (i) introduce the ideas behind ecosystem health, and assess their relation with other usage such as ‘integrity’ or ‘quality’; (ii) sketch the sorts of multidisciplinary studies that could contribute to an assessment of health of an estuary and how these must be approached in developing useful indicators; and (iii) make a case for including measurements of the rates of ecological processes in such an assessment. These rate measurements, termed ‘ecoassays’, focus on important processes such as decomposition, recruitment, predator–prey interactions, and the like. A case study is introduced wherein these processes were assessed in mangrove stands of estuaries around Sydney, New South Wales, by explicitly comparing the rates of herbivory and decomposition of mangrove leaves, attack of fallen wood by shipworms, and colonization of pneumatophores by algae, as well as with more traditional estimates of ‘standing stocks’. Not surprisingly, the different measures retrieved various patterns and the challenge now is to integrate these into a scheme that indicates something of value. The potential utility of such measures is discussed in relation to the various scientific and managerial requirements of environmental monitoring.     

Tumour‐derived exosomes: Tiny envelopes for big stories

The discovery of exosomes, which are small, 30–100 nm sized extracellular vesicles that are released by virtual all cells, has initiated a rapidly expanding and vibrant research field. Current investigations are mainly directed toward the role of exosomes in intercellular communication and their potential value as biomarkers for a broad set of diseases. By horizontal transfer of molecular information such as micro RNAs, messenger RNAs or proteins, as well as by receptor–cell interactions, exosomes are capable to mediate the reprogramming of surrounding cells. Herein, we review how especially cancer cells take advantage of this mechanism to influence their microenvironment in favour of immune escape, therapy resistance, tumour growth and metastasis. Moreover, we provide a comprehensive microarray analysis (n > 1970) to study the expression patterns of genes known to be intimately involved in exosome biogenesis across 26 different cancer entities and a normal tissue atlas. Consistent with the elevated production of exosomes observed in cancer patient plasma, we found a significant overexpression especially of RAB27A, CHMP4C and SYTL4 in the corresponding cancer entities as compared to matched normal tissues. Finally, we discuss the immune‐modulatory and anti‐tumorigenic functions of exosomes as well as innovative approaches to specifically target the exosomal circuits in experimental cancer therapy.     

Note : Cyclohexenoesculetin-β-D-glucoside: a new substrate for the detection of bacterial β-D-glucosidase

A new substrate for the detection of bacterial β- D -glucosidase was evaluated as an alternative to aesculin. This substrate, 3,4-cyclohexenoesculetin-7-β- D -glucoside, was compared with aesculin for the detection of β- D -glucosidase in 150 enterococci, 40 streptococci, 12 Listeria sp. and 250 strains of Enterobacteriaceae. In the Gram-positive strains tested, aesculin hydrolysis correlated with hydrolysis of 3,4-cyclohexenoesculetin-7-β- D -glucoside. In the Gram-negative strains the new substrate was hydrolysed by all aesculin-positive strains and also by four strains (10%) of Escherichia coli which gave a negative aesculin reaction. 3,4-Cyclohexenoesculetin-7-β- D -glucoside was shown to be a reliable alternative to aesculin and was shown to have significant advantages over aesculin when incorporated into solid media. This was due to the non-diffusible end product produced by hydrolysis of 3,4-cyclohexenoesculetin-7-β- D -glucoside in the presence of iron.     

Gating-Related Molecular Motions in the Extracellular Domain of the I<Subscript>Ks</Subscript> Channel: Implications for I<Subscript>Ks</Subscript> Channelopathy

Cardiac slow delayed rectifier (I_Ks) channel complex consists of KCNQ1 channel and KCNE1 auxiliary subunits. The extracellular juxtamembranous region of KCNE1 is an unstructured loop that contacts multiple KCNQ1 positions in a gating-state-dependent manner. Congenital arrhythmia-related mutations have been identified in the extracellular S1–S2 linker of KCNQ1. These mutations manifest abnormal phenotypes only when coexpressed with KCNE1, pointing to the importance of proper KCNQ1/KCNE1 interactions here in I_Ks channel function. We investigate the interactions between the KCNE1 loop (positions 36–47) and KCNQ1 S1–S2 linker (positions 140–148) by means of disulfide trapping and voltage clamp techniques. During transitions among the resting-state conformations, KCNE1 positions 36–43 make contacts with KCNQ1 positions 144, 145, and 147 in a parallel fashion. During conformational changes in the activated state, KCNE1 position 40 can make contacts with all three KCNQ1 positions, while the neighboring KCNE1 positions (36, 38, 39, and 41) can make contact with KCNQ1 position 147. Furthermore, KCNQ1 positions 143 and 146 are high-impact positions that cannot tolerate cysteine substitution. To maintain the proper I_Ks channel function, position 143 requires a small side chain with a hydroxyl group, and position 146 requires a negatively charged side chain. These data and the proposed molecular motions provide insights into the mechanisms by which mutations in the extracellular juxtamembranous region of the I_Ks channel impair its function.     

Hermansky–Pudlak Syndrome and Pale Ear: Melanosome‐Making for the Millennium

Hermansky–Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized principally by oculocutaneous albinism, a bleeding tendency, and a ceroid‐lipofuscin lysosomal storage disease. These clinical manifestations of HPS are associated with defects of multiple cytoplasmic organelles – melanosomes, platelet granules, and lysosomes – suggesting that the HPS gene product is involved in some shared feature of the biogenesis or functions of these diverse organelles. The HPS gene has been cloned, and a number of pathologic mutations of the gene have been identified. Functional studies indicate that the HPS protein is part of a high‐molecular weight complex involved in the biogenesis of early melanosomes. Additional disorders with similarities to HPS have been identified in man, mouse, flies, and yeast, and it is rapidly becoming clear that understanding these disorders will shed new light on the mechanisms by which cells traffic newly synthesized proteins through the cytoplasm to assemble functional organelles.     

"PolyMin": software for identification of the minimum number of polymorphisms required for haplotype and genotype differentiation

Background  

Analysis of allelic variation for relevant genes and monitoring chromosome segment transmission during selection are important approaches in plant breeding and ecology. To minimize the number of required molecular markers for this purpose is crucial due to cost and time constraints. To date, software for identification of the minimum number of required markers has been optimized for human genetics and is only partly matching the needs of plant scientists and breeders. In addition, different software packages with insufficient interoperability need to be combined to extract this information from available allele sequence data, resulting in an error-prone multi-step process of data handling.