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Notizen: Biochemical and genetic abnormalities of α-synuclein (α-Syn) are implicated in the pathogenesis of Parkinson's disease (PD) and other α-synucleinopathies. The abnormal intraneuronal accumulations of α-Syn in Lewy bodies (LBs) and Lewy neurites (LNs) have implicated defects in axonal transport of α-Syn in the α-synucleinopathies. Using human (Hu) α-Syn transgenic (Tg) mice, we have examined whether familial PD (FPD)-linked mutations (A30P and A53T) alter axonal transport of Huα-Syn. Our studies using peripheral nerves show that Huα-Syn and Moα-Syn are almost exclusively transported in the slow component (SC) of axonal transport and that the FPD-linked α-Syn mutations do not have obvious effects on the axonal transport of α-Syn. Moreover, older pre-symptomatic A53T Huα-Syn Tg mice do not show gross alterations in the axonal transport of α-Syn and other proteins in the SC, indicating that the early stages of α-synucleinopathy in A53T α-Syn Tg mice are not associated with gross alterations in the slow axonal transport. However, the axonal transport of α-Syn slows significantly with aging. Because the rate of axonal transport affects the stability and accumulation of proteins in axons, age-dependent-slowing α-Syn is a likely contributor to axonal aggregation of α-Syn in α-synucleinopathy.

Notizen: The gradual discovery that late Neoproterozoic ice sheets extended to sea level near the equator poses a palaeoenvironmental conundrum. Was the Earth's orbital obliquity 〉 60° (making the tropics colder than the poles) for 4.0 billion years following the lunar-forming impact, or did climate cool globally for some reason to the point at which runaway ice-albedo feedback created a `snowball' Earth? The high-obliquity hypothesis does not account for major features of the Neoproterozoic glacial record such as the abrupt onsets and terminations of discrete glacial events, their close association with large (〉 10‰) negative δ13C shifts in seawater proxies, the deposition of strange carbonate layers (`cap carbonates') globally during post-glacial sea-level rise, and the return of large sedimentary iron formations, after a 1.1 billion year hiatus, exclusively during glacial events. A snowball event, on the other hand, should begin and end abruptly, particularly at lower latitudes. It should last for millions of years, because outgassing must amass an intense greenhouse in order to overcome the ice albedo. A largely ice-covered ocean should become anoxic and reduced iron should be widely transported in solution and precipitated as iron formation wherever oxygenic photosynthesis occurred, or upon deglaciation. The intense greenhouse ensures a transient post-glacial regime of enhanced carbonate and silicate weathering, which should drive a flux of alkalinity that could quantitatively account for the world-wide occurrence of cap carbonates. The resulting high rates of carbonate sedimentation, coupled with the kinetic isotope effect of transferring the CO2 burden to the ocean, should drive down the δ13C of seawater, as is observed. If cap carbonates are the `smoke' of a snowball Earth, what was the `gun'? In proposing the original Neoproterozoic snowball Earth hypothesis, Joe Kirschvink postulated that an unusual preponderance of land masses in the middle and low latitudes, consistent with palaeomagnetic evidence, set the stage for snowball events by raising the planetary albedo. Others had pointed out that silicate weathering would most likely be enhanced if many continents were in the tropics, resulting in lower atmospheric CO2 and a colder climate. Negative δ13C shifts of 10–20‰ precede glaciation in many regions, giving rise to speculation that the climate was destabilized by a growing dependency on greenhouse methane, stemming ultimately from the same unusual continental distribution. Given the existing palaeomagnetic, geochemical and geological evidence for late Neoproterozoic climatic shocks without parallel in the Phanerozoic, it seems inevitable that the history of life was impacted, perhaps profoundly so.

Notizen: The purpose of this study was to compare a range of reading–related abilities in two groups of college freshmen with higher and lower reading comprehension abilities. Reading comprehension ability groups were formed using American College Test reading scores. The groups were compared on measures of oral language vocabulary and syntax, phonemic awareness and print decoding skills. Results indicated that abilities that appear to relate to reading comprehension include recognition of the order of phonemes in spoken syllables, recognition of words that are good semantic and syntactic fits for sentence frames, recall of meanings for spoken words and conversion of printed to spoken words.

Notizen: Based on the observation that some ESL learners appear to regress in performance during language learning when traditional test accuracy scores are used, another aspect of students' performance was investigated. Using a confidence-rating scale, the self-monitoring abilities of 67 intermediate ESL students enrolled in a University-level pronunciation/listening course were assessed over a seven week period and compared with test accuracy scores. Results indicated three different groups of students. A lower level group, in terms of initial test accuracy scores, improved in their ability to choose correct answers on a test but their self-monitoring ability did not improve. A middle-level group actually regressed in their ability to choose correct answers on a test but significantly improved in self-monitoring ability. The higher-level group showed only minor improvement in both ability to choose correct answers and in self-monitoring. The pedagogical implications of these findings in terms of language acquisition, teacher attitudes, and testing are discussed.

Notizen: Metronidazole (Mtz) is a critical component of combination therapies that are used against Helicobacter pylori, the major cause of peptic ulcer disease. Many H. pylori strains are Mtz resistant (MtzR), however, and here we show that MtzR results from loss of oxygen-insensitive NADPH nitroreductase activity. The underlying gene (called ‘rdxA’) was identified in several steps: transformation of Mtz-susceptible (MtzS) H. pylori with cosmids from a MtzR strain, subcloning, polymerase chain reaction (PCR) and DNA sequencing. We also found that (i) E. coli (normally MtzR) was rendered MtzS by a functional H. pylori rdxA gene; (ii) introduction of rdxA on a shuttle vector plasmid into formerly MtzRH. pylori rendered it MtzS; and (iii) replacement of rdxA in MtzSH. pylori with an rdxA::camR null insertion allele resulted in a MtzR phenotype. The 630 bp rdxA genes of five pairs of H. pylori isolates from infections that were mixed (MtzR/MtzS), but uniform in overall genotype, were sequenced. In each case, the paired rdxA genes differed from one another by one to three base substitutions. Typical rdxA genes from unrelated isolates differ by ≈ 5% in DNA sequence. Therefore, the near identity of rdxA genes from paired MtzR and MtzS isolates implicates de novo mutation, rather than horizontal gene transfer in the development of MtzR. Horizontal gene transfer could readily be demonstrated under laboratory conditions with mutant rdxA alleles. RdxA is a homologue of the classical nitroreductases (CNRs) of the enteric bacteria, but differs in cysteine content (6 vs. 1 or 2 in CNRs) and isoelectric point (pI = 7.99 vs. 5.4–5.6), which might account for its reduction of low redox drugs such as Mtz. We suggest that many rdxA (MtzR) mutations may have been selected by prior use of Mtz against other infections. H. pylori itself is an early risk factor for gastric cancer; the possibility that its carcinogenic effects are exacerbated by Mtz use, which is frequent in many societies, or the reduction of nitroaromatic compounds to toxic, mutagenic and carcinogenic products, may be of significant concern in public health.

Notizen: The genes encoding the β- and β′-subunits of RNA polymerase (rpoB and rpoC respectively) are fused as one continuous open reading frame in Helicobacter pylori and in other members of this genus, but are separate in other bacterial taxonomic groups, including the closely related genus Campylobacter. To test whether this β–β′ tethering is essential, we used polymerase chain reaction-based cloning to separate the rpoB and rpoC moieties of the H. pylori rpoB–rpoC fusion gene with a non-polar chloramphenicol resistance cassette containing a new translational start, and introduced this construct into H. pylori by electrotransformation. H. pylori containing these separated rpoB and rpoC genes in place of the native fusion gene produced non-tethered β and β′ RNAP subunits, grew well in culture and colonized and proliferated well in conventional C57BL/6 mice. Thus, the extraordinary β–β′ tethering is not essential for H. pylori viability and gastric colonization.

Notizen: This article describes the development and evolution of Library 110: Introduction to Library Research, which integrated information literacy into the curriculum through the general education program at the Univesity of Nebraska, Lincoln. By redesigning and migrating the course to an electronic environment, several benefits resulted.