Compositional turnover and variation in Eemian pollen sequences in Europe

Vegetation History and Archaeobotany - The Eemian interglacial represents a natural experiment on how past vegetation with negligible human impact responded to amplified temperature changes...     

Effects of doxorubicin cancer therapy on autophagy and the ubiquitin-proteasome system in long-term cultured adult rat cardiomyocytes

The clinical use of anthracyclines in cancer therapy is limited by dose-dependent cardiotoxicity that involves cardiomyocyte injury and death. We have tested the hypothesis that anthracyclines affect protein degradation pathways in adult cardiomyocytes. To this aim, we assessed the effects of doxorubicin (Doxo) on apoptosis, autophagy and the proteasome/ubiquitin system in long-term cultured adult rat cardiomyocytes. Accumulation of poly-ubiquitinated proteins, increase of cathepsin-D-positive lysosomes and myofibrillar degradation were observed in Doxo-treated cardiomyocytes. Chymotrypsin-like activity of the proteasome was initially increased and then inhibited by Doxo over a time-course of 48 h. Proteasome 20S proteins were down-regulated by higher doses of Doxo. The expression of MURF-1, an ubiquitin-ligase specifically targeting myofibrillar proteins, was suppressed by Doxo at all concentrations measured. Microtubule-associated protein?1 light chain 3B (LC3)-positive punctae and both LC3-I and -II proteins were induced by Doxo in a dose-dependent manner, as confirmed by using lentiviral expression of green fluorescence protein bound to LC3 and live imaging. The lysosomotropic drug chloroquine led to autophagosome accumulation, which increased with concomitant Doxo treatment indicating enhanced autophagic flux. We conclude that Doxo causes a downregulation of the protein degradation machinery of cardiomyocytes with a resulting accumulation of poly-ubiquitinated proteins and autophagosomes. Although autophagy is initially stimulated as a compensatory response to cytotoxic stress, it is followed by apoptosis and necrosis at higher doses and longer exposure times. This mechanism might contribute to the late cardiotoxicity of anthracyclines by accelerated aging of the postmitotic adult cardiomyocytes and to the susceptibility of the aging heart to anthracycline cancer therapy.     

Dispersal ability of marked,irradiated olive fruit flies [Bactrocera oleae (Rossi) (Diptera: Tephritidae)] in arid regions

The dispersal of marked, irradiated olive fruit flies originating from a hybrid laboratory strain was studied in an olive groove located in the arid regions of southern Israel. Release–recapture experiments (eight in total) were conducted throughout a period of 5 months (July–December 2008). In each experiment, ca. 5000 flies were released. Recapture of flies was conducted using a grid of 30 yellow sticky traps set in expanding semicircles from the centre of release. Service of traps was conducted 3 and 15 days after the release. Fly quality and adult food type (only sucrose and protein + sucrose) before release was also investigated. Results point at an average dispersal distance of marked, irradiated olive flies of ca. 50 m. Pre‐release adult diet did not affect dispersal ability. Fly recovery averaged ca. 3.5% during summer and ca. 1.5% during autumn. Most of the recovery concentrated during the first 3 days after releases, suggesting low survival of the released flies afterwards. As inferred from circular statistics, direction of dispersal was non‐random with a significant directionality to the north‐west. Results are discussed in view of environmental temperatures and wind direction.     

Respiratory and immune response to maximal physical exertion following exposure to secondhand smoke in healthy adults

We assessed the cardiorespiratory and immune response to physical exertion following secondhand smoke (SHS) exposure through a randomized crossover experiment. Data were obtained from 16 (8 women) non-smoking adults during and following a maximal oxygen uptake cycling protocol administered at baseline and at 0-, 1-, and 3- hours following 1-hour of SHS set at bar/restaurant carbon monoxide levels. We found that SHS was associated with a 12% decrease in maximum power output, an 8.2% reduction in maximal oxygen consumption, a 6% increase in perceived exertion, and a 6.7% decrease in time to exhaustion (P<0.05). Moreover, at 0-hours almost all respiratory and immune variables measured were adversely affected (P<0.05). For instance, FEV(1) values at 0-hours dropped by 17.4%, while TNF-α increased by 90.1% (P<0.05). At 3-hours mean values of cotinine, perceived exertion and recovery systolic blood pressure in both sexes, IL4, TNF-α and IFN-γ in men, as well as FEV(1)/FVC, percent predicted FEV(1), respiratory rate, and tidal volume in women remained different compared to baseline (P<0.05). It is concluded that a 1-hour of SHS at bar/restaurant levels adversely affects the cardiorespiratory and immune response to maximal physical exertion in healthy nonsmokers for at least three hours following SHS.     

Control of the olive fruit fly using genetics-enhanced sterile insect technique

Ubiquitin signaling pathways rely on E3 ligases for effecting the final transfer of ubiquitin from E2 ubiquitin conjugating enzymes to a protein target. Here we re-evaluate the hybrid RING/HECT mechanism used by the E3 family RING-between-RINGs (RBRs) to transfer ubiquitin to substrates. We place RBRs into the context of current knowledge of HECT and RING E3s. Although not as abundant as the other types of E3s (there are only slightly more than a dozen RBR E3s in the human genome), RBRs are conserved in all eukaryotes and play important roles in biology. Re-evaluation of RBR ligases as RING/HECT E3s provokes new questions and challenges the field.     

Hsp70 translocates to the nuclei and nucleoli, binds to XRCC1 and PARP-1, and protects HeLa cells from single-strand DNA breaks

For many years, there has been uncertainty concerning the reason for Hsp70 translocation to the nucleus and nucleolus. Herein, we propose that Hsp70 translocates to the nucleus and nucleoli in order to participate in pathways related to the protection of the nucleoplasmic DNA or ribosomal DNA from single-strand breaks. The absence of Hsp70 in HeLa cells, via Hsp70 gene silencing (knockdown), indicated the essential role of Hsp70 in DNA integrity. Therefore, HeLa Hsp70 depleted cells were very sensitive in heat treatment and their DNA breaks were multiple compared to that of control HeLa cells. The molecular mechanism with which Hsp70 performs its role at the level of nucleus and nucleolus during stress was examined. Hsp70 co-localizes with PARP1 in the nucleus/nucleoli as was observed in confocal studies and binds to the BCRT domain of PARP1 as was revealed with protein–protein interaction assays. It was also found that Hsp70 binds simultaneously to XRCC1 and PARP-1, indicating that Hsp70 function takes place at the level of DNA repair and possibly at the base excision repair system. Making a hypothetical model, we have suggested that Hsp70 is the molecule that binds and interrelates with PARP1 creating the repair proteins simultaneously, such as XRCC1, at the single-strand DNA breaks. Our data partially clarify a previously unrecognized cellular response to heat stress. Finally, we can speculate that Hsp70 plays a role in the quality and integrity of DNA. Outlining prior scientific knowledge on the subject and novel information: The role of Hsp70 translocation to the nucleus and nucleolus during heat stress has been nearly unknown. It has been proposed that this biological phenomenon is correlated to Hsp70-chaperoning activity. Furthermore, some previous observations in yeast have revealed that Rad9 complexes—Rad9 being the prototype DNA-damage checkpoint gene—contain Ssa1 and or Ssa2 chaperone proteins, both reconstituting the functions of the corresponding Hsp70 in mammalian cells. Here, we propose that Hsp70 translocates to the nuclei/nucleoli during heat stress, binds to PARP-1 and/or XRCC1, and protects HeLa cells from increased single-strand DNA breaks.     

Down-regulation of kallikrein-related peptidase 5 (<Emphasis Type="Italic">KLK5</Emphasis>) expression in breast cancer patients: a biomarker for the differential diagnosis of breast lesions

Background  

Kallikrein-related peptidase 5 (KLK5) is a secreted trypsin-like protease of the KLK family, encoded by the KLK5 gene. KLK5 has been found to cleave various extracellular matrix components, as well as to activate several other KLK proteases, triggering the stimulation of tissue microenvironment proteolytic cascades.     

Geometric morphometric 3D shape analysis and covariation of human mandibular and maxillary first molars

Dental casts of 160 Greek subjects (80 males, 80 females) were scanned by a structured‐light scanner. The upper and lower right first molar occlusal surface 3D meshes were processed using geometric morphometric methods. A total of 265 and 274 curve and surface sliding semilandmarks were placed on the upper and lower molar surfaces, respectively. Principal component analysis and partial least square analysis were performed to assess shape parameters. Molars tended to vary between an elongated and a more square form. The first two principal components (PCs), comprising almost 1/3 of molar shape variation, were related to mesiodistal–buccolingual ratios and relative cusp position. Distal cusps displayed the greatest shape variability. Molars of males were larger than those of females (2.8 and 3.2% for upper and lower molars respectively), but no shape dimorphism was observed. Upper and lower molar sizes were significantly correlated (r² = 0.689). Allometry was observed for both teeth. Larger lower molars were associated with shorter cusps, expansion of the distal cusp, and constriction of the mesial cusps (predicted variance 3.25%). Upper molars displayed weaker allometry (predicted variance 1.59%). Upper and lower molar shape covariation proved significant (RV = 17.26%, P < 0.0001). The main parameter of molar covariation in partial least square axis 1, contributing to 30% of total covariation, was cusp height, in contrast to the primary variability traits exhibited by PC1 and PC2. The aim of this study was to evaluate shape variation and covariation, including allometry and sexual dimorphism, of maxillary and mandibular first permanent molar occlusal surfaces. Am J Phys Anthropol 152:186–196, 2013. © 2013 Wiley Periodicals, Inc.     

Genetic elimination of field-cage populations of Mediterranean fruit flies

The Mediterranean fruit fly (medfly, Ceratitis capitata Wiedemann) is a pest of over 300 fruits, vegetables and nuts. The sterile insect technique (SIT) is a control measure used to reduce the reproductive potential of populations through the mass release of sterilized male insects that mate with wild females. However, SIT flies can display poor field performance, due to the effects of mass-rearing and of the irradiation process used for sterilization. The development of female-lethal RIDL (release of insects carrying a dominant lethal) strains for medfly can overcome many of the problems of SIT associated with irradiation. Here, we present life-history characterizations for two medfly RIDL strains, OX3864A and OX3647Q. Our results show (i) full functionality of RIDL, (ii) equivalency of RIDL and wild-type strains for life-history characteristics, and (iii) a high level of sexual competitiveness against both wild-type and wild-derived males. We also present the first proof-of-principle experiment on the use of RIDL to eliminate medfly populations. Weekly releases of OX3864A males into stable populations of wild-type medfly caused a successive decline in numbers, leading to eradication. The results show that genetic control can provide an effective alternative to SIT for the control of pest insects.