ATP‐dependent DNA binding,unwinding, and resection by the Mre11/Rad50 complex

ATP‐dependent DNA end recognition and nucleolytic processing are central functions of the Mre11/Rad50 (MR) complex in DNA double‐strand break repair. However, it is still unclear how ATP binding and hydrolysis primes the MR function and regulates repair pathway choice in cells. Here, Methanococcus jannaschii MR‐ATPγS‐DNA structure reveals that the partly deformed DNA runs symmetrically across central groove between two ATPγS‐bound Rad50 nucleotide‐binding domains. Duplex DNA cannot access the Mre11 active site in the ATP‐free full‐length MR complex. ATP hydrolysis drives rotation of the nucleotide‐binding domain and induces the DNA melting so that the substrate DNA can access Mre11. Our findings suggest that the ATP hydrolysis‐driven conformational changes in both DNA and the MR complex coordinate the melting and endonuclease activity.     

Central insulin‐like growth factor‐1 (IGF‐1) restores whole‐body insulin action in a model of age‐related insulin resistance and IGF‐1 decline

Low insulin‐like growth factor‐1 (IGF‐1) signaling is associated with improved longevity, but is paradoxically linked with several age‐related diseases in humans. Insulin‐like growth factor‐1 has proven to be particularly beneficial to the brain, where it confers protection against features of neuronal and cognitive decline. While aging is characterized by central insulin resistance in the face of hyperinsulinemia, the somatotropic axis markedly declines in older humans. Thus, we hypothesized that increasing IGF‐1 in the brain may prove to be a novel therapeutic alternative to overcome central insulin resistance and restore whole‐body insulin action in aging. Utilizing hyperinsulinemic‐euglycemic clamps, we show that old insulin‐resistant rats with age‐related declines in IGF‐1 level demonstrate markedly improved whole‐body insulin action, when treated with central IGF‐1, as compared to central vehicle or insulin (P < 0.05). Furthermore, central IGF‐1, but not insulin, suppressed hepatic glucose production and increased glucose disposal rates in aging rats (P < 0.05). Taken together, IGF‐1 action in the brain and periphery provides a ‘balance’ between its beneficial and detrimental actions. Therefore, we propose that strategies aimed at ‘tipping the balance’ of IGF‐1 action centrally are the optimal approach to achieve healthy aging and longevity in humans.     

Biostratigraphy of the Peri-Gondwana Cambrian trilobite fauna (northern Kerman,Iran) and correlation with other countries

Polymeroid trilobite fauna from two stratigraphic sections (Godbondar and Kuhbanan) of the Kuhbanan Formation in northern Kerman (central Iran) were studied and subjected to biostratigraphic analysis. Eleven genera and species are recognised from the latest Early Cambrian and Middle Cambrian Peri-Gondwanian successions of the study sections. The recognised fauna includes Afghanocare lategenatum, Blountia blountia, Iranoleesia sp., Iranoleesia pisiformis, Kermanella kuhbananensis, Kermanella lata lata, Kermanella lata minuta, Kermanella sp., Redlichia chinensis, Redlichia noetlingi and Redlichia sp. Based on trilobite distribution, three trilobite biozones were recognised in the study sections, namely Redlichia noetlingi biozone, Kermanella kuhbananensis biozone and Iranoleesia pisiformis biozone. The age of the study sections is late Early Cambrian to late Middle Cambrian based on the recognised trilobite biozones. The recognised late Early Cambrian trilobite assemblages (especially Redlichia and Kermanella) from northern Kerman are similar to those found from some other parts of Gondwana or Peri-Gondwana terrains (north India, Pakistan, northwestern Kashmir, Tajikistan, South Australia, South China and Afghanistan) and show affinities with fauna found in some other parts of Iran (Alborz, northern Iran; Tabas, eastern Iran; southeast Karman).     

A Double‐Edged Sword: Complement Component 3 in Toxoplasma gondii Infection

Sprague Dawley rats and Kunming (KM) mice are artificially infected with type II Toxoplasma gondii strain Prugniaud (Pru) to generate toxoplasmosis, which is a fatal disease mediated by T. gondii invasion of the central nervous system (CNS) by unknown mechanisms. The aim is to explore the mechanism of differential susceptibility of mice and rats to T. gondii infection. Therefore, a strategy of isobaric tags for relative and absolute quantitation (iTRAQ) is established to identify differentially expressed proteins (DEPs) in the rats’ and the mice's brains compared to the healthy groups. In KM mice, which is susceptible to T. gondii infection, complement component 3 (C3) is upregulated and the tight junction (TJ) pathway shows a disorder. It is presumed that T. gondii‐stimulated C3 disrupts the TJ of the blood–brain barrier in the CNS. This effect allows more T. gondii passing to the brain through the intercellular space.     

New pollen classification of Chenopodiaceae for exploring and tracing desert vegetation evolution in eastern arid central Asia

Members of the Chenopodiaceae are the most dominant elements in the central Asian desert. The different genera and species within this family are common in desert vegetation types. Should it prove possible to link pollen types in this family to specific desert vegetation, it would be feasible to trace vegetation successions in the geological past. Nevertheless, the morphological similarity of pollen grains in the Chenopodiaceae rarely permits identification at the generic level. Although some pollen classifications of Chenopodiaceae have been proposed, none of them tried to link pollen types to specific desert vegetation types in order to explore their ecological significance. Based on the pollen morphological characters of 13 genera and 24 species within the Chenopodiaceae of eastern central Asia, we provide a new pollen classification of this family with six pollen types and link them to those plant communities dominated by Chenopodiaceae, for example, temperate dwarf semi‐arboreal desert (Haloxylon type), temperate succulent halophytic dwarf semi‐shrubby desert (Suaeda, Kalidium, and Atriplex types), temperate annual graminoid desert (Kalidium type), temperate semi‐shrubby and dwarf semi‐shrubby desert (Kalidium, Iljini, and Haloxylon types), and alpine cushion dwarf semi‐shrubby desert (Krascheninnikovia type). These findings represent a new approach for detecting specific desert vegetation types and deciphering ecosystem evolution in eastern central Asia.     

A phase II randomized clinical trial for the treatment of recalcitrant chronic leg ulcers using centrifuged adipose tissue containing progenitor cells

Background aims

Preclinical and observational reports indicate that adipose tissue (AT) is a safe and promising tool to treat non-healing venous leg ulcers (VLUs).

Syntaxonomy of the Robinia pseudoacacia communities in the central peri-adriatic sector of the Italian peninsula

This study presents the results of a floristic vegetational study on Robinia pseudoacacia neoformation forests in the peri-Adriatic sector of central Italy. This has allowed the characterization of these coenoses at the ecological, biogeographic, syntaxonomic and landscape levels. These currently represent the southernmost syntaxa of the Robinietea class described for the Italian peninsula, and the first syntaxonomic contribution of this class in Europe for the Mediterranean biogeographical region. We propose here the new alliance Lauro nobilis–Robinion pseudoacaciae of the order Chelidonio–Robinietalia pseudoacaciae and class Robinietea, with two new associations: Melisso altissimae–Robinietum pseudoacaciae and Rubio peregrinae–Robinietum pseudoacaciae. The new alliance Lauro nobilis–Robinion pseudoacaciae (typus: Melisso altissimae–Robinietum pseudoacaciae) brings together neoformation forests and pre-forest dominated by R. pseudoacacia in those territories with a Mediterranean macroclimate of the peri-Adriatic sector of central Italy. The optimum is found for the alluvial plain and low-slope morphologies, on soils that are moist and rich in organic matter and in areas with anthropic disturbance. On the basis of comparisons with the European context, the alliance Bryonio–Robinion described for the temperate territories of northern Italy is here validated.     

Comparative study on different therapies on patients with primary central nervous system lymphoma

Objective

To compare and analyze three therapies on patients with primary central nervous system lymphoma (PCNSL), aiming to provide evidences for future treatment and prognosis.

Developmentally Arrested Precursors of Pontine Neurons Establish an Embryonic Blueprint of the Drosophila Central Complex

1. Download high-res image (290KB)
2. Download full-size image

     

Spatio‐temporal gradients in food supply help explain the short‐term colonisation dynamics of the critically endangered central rock‐rat (Zyzomys pedunculatus)

Currently, the impact of introduced predators on small mammal population decline is a focal research direction in the Australian desert literature. In all likelihood though, single‐factor explanation of population dynamics is inadequate, leaving gaps in our knowledge of the multitude of potential influences on small mammal abundance and occupancy patterns in time and space. Here, we investigated floristic gradients across four potential refuge sites of the central rock‐rat, Zyzomys pedunculatus, a granivore rodent (50–120 g) that is endemic to central Australia and is categorised as critically endangered. The study took place in Tjoritja/West MacDonnell National Park in the MacDonnell Ranges bioregion. Floristic sampling was allocated across the four sites, the locations of which were predetermined by an established monitoring and management programme for the central rock‐rat. Our aim was to examine the relationship between environmental gradients and floristic composition across the four sites, and thereby test the extent to which the patterns of food type and food availability can inform central rock‐rat spatio‐temporal dynamics. We found high site‐scale floristic patterning that related foremost to elevation and then to antecedent rainfall and time‐since‐fire and fire‐severity effects. To interpret these results, we applied the principles of refuge theory and we described a gradient from core refuge habitat to intermittent and then marginal habitat within the current central rock‐rat stronghold area. Overall, our results implied a strong floristic basis to central rock‐rat site occurrence, and they thus compel us to take explicit account of spatial (elevation) and temporal (rainfall–productivity and fire‐disturbance) influences on the food axis of potential refuge sites of this critically endangered species.