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Hydrogen–deuterium exchange mass spectrometry (HDX MS) has become an important technique for the analysis of protein structure and dynamics. Data analysis remains a bottleneck in the workflow. Sophisticated computer analysis is required to scan through the voluminous MS output in order to find, identify, and validate many partially deuterated peptides, elicit the HDX information, and extend the results to higher structural resolution. We previously made available two software suites, ExMS for identification and analysis of peptide isotopic envelopes in the HDX MS raw data and HDsite for residue-level resolution. Further experience has led to advances in the usability and performance of both programs. Also, newly added modules deal with ETD/ECD analysis, multimodal mass spectra analysis, and presentation options. These advances have been integrated into a stand-alone software solution named ExMS2. The package has been successfully tested by many workers in fine scale epitope mapping, in protein folding studies, and in dissecting structure and structure change of large protein complexes. A description and tutorial for this major upgrade are given here.

Chromosomes in human cells are protected by telomeres. Telomere shortens during each round of cell division because of the DNA end-replication problem. Cancer cells maintain telomere length homeostasis by either telomerase or/and the alternative lengthening of telomere (ALT) mechanism to sustain their division potential. Telomeric DNA tends to form G-quadruplex preferentially at the extreme 3’ end. This unique feature prevents the 3’ end from being used as a substrate of telomerase and as a primer in the ALT. Therefore, stabilizing telomere G-quadruplex is expected to inhibit both pathways and limit the proliferation of cancer cells. Based on a mathematical modeling and experimental results, this mini-review proposes a hypothesis that the formation of G-quadruplex in telomere may constitute a significant contribution to the incomplete end-replication of telomere DNA by preventing the priming of DNA synthesis near the 3’ end during telomere replication. According to this, stabilization of telomere G-quadruplex by chemical ligand may promise to accelerate telomere shortening in proliferating cells.

Eine Frage der Geschwindigkeit: In einer K+/Polyethylenglycol‐haltigen Lösung falten Guanin(G)‐reiche Stränge aus telomerer Wirbeltier‐DNA innerhalb von Mikrosekunden in parallele/antiparallele G‐Quadruplexe –(3+1)‐Hybride –, bevor sie sich anschließend innerhalb von Stunden in parallele Strukturen umwandeln (siehe Abbildung). Daher ist die Konformation, die ein G‐Quadruplex zunächst unter physiologischen Bedingungen annimmt, nicht die des Gleichgewichtszustandes.

A matter of speed: When allowed to fold in a K+/poly(ethylene glycol) solution, the guanine (G)‐rich strand of vertebrate telomere DNA forms a parallel/antiparallel G‐quadruplex, which is a (3+1) hybrid, within microseconds before slowly transforming into the parallel one within hours (see picture). Thus, the conformation that a G‐quadruplex initially adopts under physiological conditions may not be the one it adopts at the equilibrium state.

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WNTs play key roles in development and disease, signaling through Frizzled (FZD) seven-pass transmembrane receptors and numerous co-receptors including ROR and RYK family receptor tyrosine kinases (RTKs). We describe crystal structures and WNT-binding characteristics of extracellular regions from the DrosophilaROR and RYK orthologs Nrk (neurospecific receptor tyrosine kinase) and Derailed-2 (Drl-2), which bind WNTs though a FZD-related cysteine-rich domain (CRD) and WNT-inhibitory factor (WIF) domain respectively. Our crystal structures suggest that neither Nrk nor Drl-2 can accommodate the acyl chain typically attached to WNTs. The Nrk CRD contains a deeply buried bound fatty acid, unlikely to be exchangeable. The Drl-2 WIF domain lacks the lipid-binding site seen in WIF-1. We also find that recombinant DWnt-5 can bind DrosophilaROR and RYK orthologs despite lacking an acyl chain. Alongside analyses of WNT/receptor interaction sites, our structures provide further insight into how WNTs may recruit RTK co-receptors into signaling complexes.

The use of latest Pleistocene-Holocene paleosols in defining Chinese climatic sequences is plagued by poor chronological controls caused primarily by the use of radiocarbon dates derived from bulk soil carbon. Dating of a post-glacial aeolian/paleosol sequence in the Pigeon Mountain basin of north-central China, using culturally deposited charcoal, support a wide array of other data suggesting the Younger Dryas was a period of cooler dryer conditions marked by wide-spread aeolian deposition. Periods of soil formation and higher lake levels bracket this climatic event. Climatic variability immediately before, during and immediately after the Younger Dryas interval is associated with rapid technological elaboration and innovation in the production and use of chipped stone tools, and perhaps, ground stone. © 1998 John Wiley & Sons, Inc.

The use of latest Pleistocene‐Holocene paleosols in defining Chinese climatic sequences is plagued by poor chronological controls caused primarily by the use of radiocarbon dates derived from bulk soil carbon. Dating of a post‐glacial aeolian/paleosol sequence in the Pigeon Mountain basin of north‐central China, using culturally deposited charcoal, support a wide array of other data suggesting the Younger Dryas was a period of cooler dryer conditions marked by wide‐spread aeolian deposition. Periods of soil formation and higher lake levels bracket this climatic event. Climatic variability immediately before, during and immediately after the Younger Dryas interval is associated with rapid technological elaboration and innovation in the production and use of chipped stone tools, and perhaps, ground stone. © 1998 John Wiley & Sons, Inc.

Survey along the margins of the Helan Mountains in the Ningxia Hui and Nei Mongol Autonomous Regions discloses variability in the distribution and assemblage composition among 47 archaeological localities, and suggests a reduction in hunter –gatherer residential mobility through time. Late Palaeolithic tool assemblages are less frequent, smaller, and relatively uniform from site to site. They tend to be found near canyon mouths on the mountain front, or around springs in the middle to upper reaches of fans, suggesting limited variation in both length of stay and subsistence strategies. In contrast, early Neolithic sites, more abundant and variable in size and complexity, are located near fan toes or lower fan springs where water could be more easily diverted. Larger more diverse assemblages suggest long-term residential bases, while smaller specialized assemblages, devoid of microliths, indicate short-term camps and resource processing locations. This helps confirm a similar pattern identified in materials collected by the Sino-Swedish expedition, in the northern Alashan. Together they suggest that the trend towards decreased residential mobility is associated with increasingly intensive and specialized use of seed resources that may be related to the early development of plant husbandry.