PDK1-mediated activation of MRCKα regulates directional cell migration and lamellipodia retraction

Directional cell migration is of paramount importance in both physiological and pathological processes, such as development, wound healing, immune response, and cancer invasion. Here, we report that 3-phosphoinositide-dependent kinase 1 (PDK1) regulates epithelial directional migration and invasion by binding and activating myotonic dystrophy kinase–related CDC42-binding kinase α (MRCKα). We show that the effect of PDK1 on cell migration does not involve its kinase activity but instead relies on its ability to bind membrane phosphatidylinositol (3,4,5)-trisphosphate. Upon epidermal growth factor (EGF) stimulation, PDK1 and MRCKα colocalize at the cell membrane in lamellipodia. We demonstrate that PDK1 positively modulates MRCKα activity and drives its localization within lamellipodia. Likewise, the retraction phase of lamellipodia is controlled by PDK1 through an MRCKα-dependent mechanism. In summary, we discovered a functional pathway involving PDK1-mediated activation of MRCKα, which links EGF signaling to myosin contraction and directional migration.     

Solar UV-B radiation modifies the proportion of volatile organic compounds in flowers of field-grown grapevine (Vitis vinifera L.) cv. Malbec

Ultraviolet-B solar radiation (UV-B) is an environmental signal with biological effects in different plant tissues. Recent investigations reported dramatic changes of terpenes with a protective role in plant tissues submitted to biotic and abiotic stresses. This study examined the volatile organic compounds (VOCs) profile in flowers of Vitis vinifera L. cv. Malbec under filtered UV-B (or not). Gas chromatography–electron impact mass spectrometry analysis of flowers resulted in the identification of 12 VOCs, including eight sesquiterpenes, two aldehydes, and two ketones, being the oxygenated sesquiterpene farnesol the most abundant. The total amount of VOCs in flowers did not change irrespective UV-B had been filtered or not, suggesting those compounds have a protective role that is constitutive of the reproductive tissues. However UV-B increases the proportion of valencene, β-farnesene, α-panasinsene and hepatriacontanedione which would require further investigation.     

Thyreophagus corticalis as a vector of hypovirulence in Cryphonectria parasitica in chestnut stands

The natural spread of hypovirulence in Cryphonectria parasitica (Murr.) Barr. occurs in chestnut (Castanea sativa Mill) stands and orchards in Italy and other European countries, leading to spontaneous recovery of the diseased trees. Little is known about how hypovirulence spreads in chestnut stands but various corticolous mite species frequently detected on chestnut cankers could be one of the many factors playing a role in the spread. Artificial virulent cankers created in inoculation field tests and treated with Thyreophagus corticalis (Acari, Sarcoptiformes, Acaridae) raised on hypovirulent cultures showed similar growth to those treated with mycelia of the hypovirulent strain over 18 months of inoculation. Cultures re-isolated from virulent cankers treated with mites were found to contain hypovirus like those derived from pairings of virulent and hypovirulent strains. Viral dsRNA could be carried externally and/or ingested by mites from the hypovirulent mycelia and then transmitted to the mycelia of virulent strains, causing their conversion. In a laboratory study, all fecal pellets collected from mites reared on hypovirulent and virulent strains grown on semi-selective media gave rise to colonies of C. parasitica with similar morphological characters and virulence to the original cultures. Field inoculation of stump sprouts with the resulting colonies revealed that mite digestive tract passage did not alter the virulence of the studied strains. These results are of interest for the biological control of chestnut blight.     

Prevalencia de sarcopenia en consultas de geriatría y residencias. Estudio ELLI

Background

There are few systematic studies on the prevalence of sarcopenia using the new diagnostic criteria in different geriatric care settings.

Objective

To estimate the prevalence of sarcopenia, using the European Working Group on Sarcopenia in Older People (EWGSOP) criteria in older subjects living in nursing homes and in those who attend geriatric outpatient clinics.

Material and methods

A single country multicentre study in two samples of older subjects: patients cared for in outpatient geriatric clinics, and individuals living in nursing homes. Data collected will include demographic variables, medical history, medication, geriatric syndromes, functional status (assessment of basic and instrumental activities of daily living), mobility, cognitive status, comorbidity, quality of life, nutritional status, and laboratory parameters. For the diagnosis of sarcopenia, 4 m walking speed, handgrip strength, and body composition measured by bioelectrical impedance analysis will be assessed.

Results

Using the EWGSOP algorithm, the prevalence of sarcopenia in an elderly Spanish population will be estimated. In addition, concordance and correlation between the three parameters included in the definition (muscle mass, muscle strength, and physical performance) will be analysed, using the different existing cut-off points, and examining the diagnostic accuracy of each. Finally, demographic, anthropometric and functional data that define subjects with sarcopenia will be investigated.

Conclusions

The ELLI study should improve knowledge on the prevalence and characteristics of sarcopenia in older people in our population.     

A mammary adenocarcinoma murine model suitable for the study of cancer immunoediting

Background

Cancer immunoediting is a dynamic process composed of three phases: elimination (EL), equilibrium (EQ) and escape (ES) that encompasses the potential host-protective and tumor-sculpting functions of the immune system throughout tumor development. Animal models are useful tools for studying diseases such as cancer. The present study was designed to characterize the interaction between mammary adenocarcinoma M-406 and CBi, CBi⁻ and CBi/L inbred mice lines.

Results

The mammary adenocarcinoma M-406 developed spontaneously in a CBi mouse. CBi/L and CBi⁻ mice were artificially selected for body conformation from CBi. When CBi mice are s.c. challenged with M-406, tumor growths exponentially in 100% of animals, while in CBi⁻ the tumor growths briefly and then begins a rejection process in 100% of the animals. In CBi/L the growth of the tumor shows the three phases: 51.6% in ES, 18.5% in EQ and 29.8% in EL.

Conclusions

The results obtained support the conclusion that the system M-406 plus the inbred mouse lines CBi, CBi⁻ and CBi/L, is a good murine model to study the process of tumor immunoediting.     

Biotransformation of Colchicinoids into Their Corresponding 3-O-Glucosyl Derivatives by Selected Strains of Bacillus megaterium

Natural colchicinoids and their semisynthetic derivatives are important active ingredients for pharmaceutical applications. Thiocolchicoside (3-demethoxy-3-glucosyloxythiocolchicine) is used in several countries as standard therapy for the treatment of diseases of the muscle–skeletal system, due to its potent antiinflammatory and myorelaxant properties. Manufacturing of thiocolchicoside requires a key step, the regioselective demethylation and glucosylation of chemically derivative thiocolchicine. High selectivity and efficiency of this transformation cannot be achieved in a satisfactory way with a chemical approach. In particular, the chemical demethylation, a part from requiring toxic and aggressive reagents, generates a complex mixture of products with no industrial usefulness. We report herein an efficient, direct and green biotransformation of thiocolchicine into thiocolchicoside, performed by a specific strain of Bacillus megaterium. The same process, with minor modifications, can be used to convert the by-product 3-O-demethyl-thiocolchicine into thiocolchicoside. In addition, we describe the B. megaterium strain selection process and the best conditions for this effective double biotransformation. The final product has a pharmaceutical quality, and the process has been industrialised.     

Diversity and biogeographical makeup of the dung beetle communities inhabiting two mountains in the Mexican Transition Zone

The role of horizontal and vertical colonization on the diversity and integration of the dung beetle fauna of two mountains in the Mexican Transition Zone (Los Tuxtlas and La Chinantla) are analyzed and compared. On each mountain standardized sampling was done using pitfall traps baited with dung and carrion along elevation gradients. On both mountains diversity decreased linearly with increasing elevation. The decrease in the number of genera and species was not different between mountains, but the cumulative total number for both taxonomic levels was significantly higher on La Chinantla. There, three well-defined groups were identified for which species turnover was mainly a result of species gain. On Los Tuxtlas there was no evident grouping pattern, and species turnover was determined by species loss. For both mountains the dominant biogeographic distribution pattern was Neotropical; however, at the higher elevations of La Chinantla, a clear replacement by lineages of Holarctic affinity was observed. We suggest that for La Chinantla—a mountain that is geographically connected to the Sierra Madre Oriental mountain range and is of ancient geological origin—the processes of horizontal and vertical colonization have had relatively different weights in terms of their effect on the pattern of diversity and the biogeographic integration of the beetle community, while on Los Tuxtlas, the limited role of horizontal colonization appears to be a consequence of its isolation and more recent geological origin. We discuss the potential use of these models for studying the effects of climate change on elevation gradients.