Pink-beam serial crystallography.

Serial X-ray crystallography allows macromolecular structure determination at both X-ray free electron lasers (XFELs) and, more recently, synchrotron sources. The time resolution for serial synchrotron crystallography experiments has been limited to millisecond timescales with monochromatic beams. The polychromatic, "pink", beam provides a more than two orders of magnitude increased photon flux and hence allows accessing much shorter timescales in diffraction experiments at synchrotron sources. Here we report the structure determination of two different protein samples by merging pink-beam diffraction patterns from many crystals, each collected with a single 100 ps X-ray pulse exposure per crystal using a setup optimized for very low scattering background. In contrast to experiments with monochromatic radiation, data from only 50 crystals were required to obtain complete datasets. The high quality of the diffraction data highlights the potential of this method for studying irreversible reactions at sub-microsecond timescales using high-brightness X-ray facilities.

Chronic ethanol consumption increases myocardial mitochondrial DNA mutations: a potential contribution by mitochondrial topoisomerases.

AIMS: Alcoholic cardiomyopathy (ACM) presents as decreased myocardial contractility, arrhythmias and secondary non-ischemic dilated cardiomyopathy leading to heart failure. Mitochondrial dysfunction is known to have a significant role in the development and complications of ACM. This study investigated if chronic ethanol feeding promoted myocardial mitochondrial topoisomerase dysfunction as one underlying cause of mitochondrial DNA (mtDNA) damage and mitochondrial dysfunction in ACM. METHODS: The impact of chronic ethanol exposure on the myocardial mitochondria was examined in both neonatal cardiomyocytes using 50 mM ethanol for 6 days and in rats assigned to control or ethanol feeding groups for 4 months. RESULTS: Chronic ethanol feeding led to significant (P < 0.05) decreases in M-mode Fractional Shortening, ejection fraction, and the cardiac output index as well as increases in Tau. Ethanol feeding promoted mitochondrial dysfunction as evidenced by significantly decreased left ventricle cytochrome oxidase activity and decreases in mitochondrial protein content. Both in rats and in cultured cardiomyocytes, chronic ethanol presentation significantly increased mtDNA damage. Using isolated myocardial mitochondria, both mitochondrial topoisomerase-dependent DNA cleavage and DNA relaxation were significantly altered by ethanol feeding. CONCLUSION: Chronic ethanol feeding compromised cardiovascular and mitochondrial function as a result of a decline in mtDNA integrity that was in part the consequence of mitochondrial topoisomerase dysfunction. Understanding the regulation of the mitochondrial topoisomerases is critical for protection of mtDNA, not only for the management of alcoholic cardiomyopathy, but also for the many other clinical treatments that targets the topoisomerases in the alcoholic patient.

The role of syllabic structure in French visual word recognition.

Two experiments are reported in which the processing units involved in the reading of French polysyllabic words are examined. A comparison was made between units following the maximal onset principle (i.e., the spoken syllable) and units following the maximal coda principle (i.e., the basic orthographic syllabic structure [BOSS]). In the first experiment, it took longer to recognize that a syllable was the beginning of a word (e.g., the FOE of FOETUS) than to make the same judgment of a BOSS (e.g., FOET). The fact that a BOSS plus one letter (e.g., FOETU) also took longer to judge than the BOSS indicated that the maximal coda principle applies to the units of processing in French. The second experiment confirmed this, using a lexical decision task with the different units being demarcated on the basis of color. It was concluded that the syllabic structure that is so clearly manifested in the spoken form of French is not involved in visual word recognition.

Syllables and morphemes: contrasting frequency effects in Spanish.

Three types of sublexical units were studied in Spanish visual word recognition: the syllable, the basic orthographic syllabic structure (BOSS), and the root morpheme. In Experiment 1, using a lexical-decision task, a typical inhibitory effect of the first-syllable frequency was found (while keeping constant the BOSS frequency) as well as the word-frequency effect. Experiment 2 examined the role of both the BOSS frequency and the word frequency, also in a lexical-decision task. Syllable frequency was controlled. Both the BOSS frequency and the word frequency showed facilitatory effects. However, in Experiments 3A and 3B, a facilitatory effect of the root frequency (when controlling for BOSS frequency) and a null effect of BOSS frequency (when controlling for root frequency) were found, suggesting that the BOSS effect is in fact reflecting a morpheme effect. A review of the current models shows that it is difficult to integrate syllables and morphemes in a unique model.

Processing of orthographic structure by adults of different reading ability.

The research presented here examines the proposal that orthographic processing in reading polysyllabic words takes place via an analysis of the word into an orthographic/morphological structure called the Basic Orthographic Syllabic Structure or BOSS. This structure includes the largest possible coda in the first component (e.g., the THUND of THUNDER) and, as such, it cuts across the phonological syllable boundary (e.g., THUN + DER). The existence of the BOSS has been previously supported by showing that words physically divided at their BOSS (e.g., THUND ER) are faster to recognize than those divided at their syllable (e.g., THUN DER). However, there has been little, if any, report of confirmatory evidence for this conclusion. Three experiments are reported here demonstrating that whether the BOSS division is faster than the syllable division depends crucially on the reading ability of the participants. Better adult reading, independently measured in terms of comprehension, is associated with a preference for the BOSS division while poorer adult reading is more associated with a syllable preference. Such a result potentially explains the conflicting findings that have been previously reported. A number of different explanations are offered for the pattern of results, with the suggestion that poorer adult reading is more oriented toward the pronunciation of the word than is better reading.

Lexical representation of gender: a quasiregular domain.

The relationship between gender and word ending in French is a quasiregular one (e.g., most words ending in -ette are feminine, but not all). As such, the gender of low-frequency irregular forms (e.g., squelette, which is masculine) should take longer to classify than low-frequency regular forms according to neural network models. A regularity effect was found in Experiment 1, but it did not interact with word frequency. It was further revealed that there was difficulty in making gender decisions (Experiment 2) and gender verification responses (Experiment 3) to words whose endings were highly informative of gender, but whose associated article was not. These words were place names beginning with a vowel, like Australie, which do not take an indefinite article and whose definite article is ambiguous (1'). How a neural network might handle these results is discussed, and an alternative account is considered whereby there are two potential sources of gender information, lexical and nonlexical, with the latter being used to confirm the former.

Bodies, antibodies, and neighborhood-density effects in masked form priming.

Facilitatory priming effects due to similarity of orthographic form are obtained for high-N target words provided that they have low-frequency bodies and the body is shared between the prime and target (e.g., perd-HERD). Conversely, it is shown that low-N target words show priming regardless of the frequency of the body, provided that the prime and target do not share the same body (e.g., drice-DRIVE). If the body is shared, then priming occurs only for targets with low-frequency bodies. These results suggest that neighborhood density should be defined in terms of both individual letter units and subsyllabic units and that both types of density jointly determine priming.