Acute sun damage and photoprotective responses in whales

Rising levels of ultraviolet radiation (UVR) secondary to ozone depletion are an issue of concern for public health. Skin cancers and intraepidermal dysplasia are increasingly observed in individuals that undergo chronic or excessive sun exposure. Such alterations of skin integrity and function are well established for humans and laboratory animals, but remain unexplored for mammalian wildlife. However, effects are unlikely to be negligible, particularly for species such as whales, whose anatomical or life-history traits force them to experience continuous sun exposure. We conducted photographic and histological surveys of three seasonally sympatric whale species to investigate sunburn and photoprotection. We find that lesions commonly associated with acute severe sun damage in humans are widespread and that individuals with fewer melanocytes have more lesions and less apoptotic cells. This suggests that the pathways used to limit and resolve UVR-induced damage in humans are shared by whales and that darker pigmentation is advantageous to them. Furthermore, lesions increased significantly in time, as would be expected under increasing UV irradiance. Apoptosis and melanocyte proliferation mirror this trend, suggesting that whales are capable of quick photoprotective responses. We conclude that the thinning ozone layer may pose a risk to the health of whales and other vulnerable wildlife.     

Highly selective c-Jun N-terminal kinase (JNK) 3 inhibitors with in vitro CNS-like pharmacokinetic properties II. Central core replacement

In this Letter, we describe the evolution of selective JNK3 inhibitors from 1, that routinely exhibit >10-fold selectivity over JNK1 and >1000-fold selectivity over related MAPKs. Strong SAR was found for substitution of the naphthalene ring, as well as for inhibitors adopting different central scaffolds. Significant potency gains were appreciated by inverting the polarity of the thione of the parent triazolothione 1, resulting in potent compounds with attractive pharmacokinetic profiles.     

Desulfurization of 2-thiouracil nucleosides: conformational studies of 4-pyrimidinone nucleosides

4-Pyrimidinone ribofuranoside (H(2)o(4)U) and 4-pyrimidinone 2'-deoxyribofuranoside (dH(2)o(4)U) were synthesized by the oxidative desulfurization of parent 2-thiouracil nucleosides with m-chloroperbenzoic acid. The crystal structures of H(2)o(4)U and dH(2)o(4)U and their conformations in solution were determined and compared with corresponding 2-thiouracil and uracil nucleosides. The absence of a large 2-thiocarbonyl/2-carbonyl group in the nucleobase moiety results in C2'-endo puckering of the ribofuranose ring (S conformer) in the crystal structure of H(2)o(4)U, which is not typical of RNA nucleosides. Interestingly, the hydrogen bonding network in the crystals of dH(2)o(4)U stabilizes the sugar moiety conformation in the C3'-endo form (N conformer), rarely found in DNA nucleosides. In aqueous solution, dH(2)o(4)U reveals a similar population of the C2'-endo conformation (65%) to that of 2'-deoxy-2-thiouridine (62%), while the 62% population of the S conformer for H(2)o(4)U is significantly different from that of the parent 2-thiouridine, for which the N conformer is dominant (71%). Such a difference may be of biological importance, as the desulfurization process of natural tRNA 2-thiouridines may occur under conditions of oxidative stress in the cell and may influence the decoding process.     

Amyrin esters induce cell death by apoptosis in HL-60 leukemia cells

Four derivatives of an α,β-amyrin mixture were synthesized by acylation with appropriate anhydrides. The structures of the compounds were confirmed by means of IR and (1)H and (13)C NMR. The compounds were screened for cytotoxic activity using four human tumor cell lines (HL-60, MDAMB-435, SF-295 and HCT-8) and normal peripheral blood mononuclear cells (PBMC). 3-O-Carboxymaleinate of α,β-amyrin (3a/3b) were found to be the only active compounds of the series (high cytotoxicity), showing IC(50) values ranging from 1.8 to 3μM. In PBMC, 3a/3b were not toxic, suggesting selectivity for tumor cells. To better understand the mechanism of action involved in the cytotoxicity of 3a/3b, HL-60 cells treated with 3a/3b were examined for morphological changes, DNA fragmentation, cell cycle perturbation, externalization of phosphatidylserine and activation of caspases 3/7, with doxorubicin serving as the positive control. The results indicate that the cytotoxicity of 3a/3b involves the induction of cell death by apoptosis.     

No costs on freeze tolerance in genetically copper adapted earthworm populations (Dendrobaena octaedra)

For nearly three centuries the area around Gusum, in south-east Sweden, has been highly polluted with copper. An earlier study in this area showed that populations of the freeze-tolerant earthworm Dendrobaena octaedra were genetically adapted to copper. Apparently, no life-history costs to reproduction or growth were imposed by this adaptation. In the present paper we therefore investigated how laboratory raised F1-generations of these populations coped when exposed to increased copper concentrations in the soil and to sub-zero temperatures. We found that D. octaedra from polluted sites accumulated the same amount of copper as reference worms. Furthermore, earthworms from polluted sites survived equally to reference worms when exposed to freezing temperatures (-8 or -12°C). However, when simultaneously exposed to the lowest temperature and copper, the worms from polluted sites survived significantly better than reference worms. The overall conclusion of this study is that worms from polluted sites seem to be better at handling copper and accrue no costs in terms of reduced cold tolerance in connection to genetic adaptation in these populations.     

Genetic diversity,genetic drift and mixed mating system in small subpopulations of <Emphasis Type="Italic">Dyckia ibiramensis</Emphasis>, a rare endemic bromeliad from Southern Brazil

Dyckia ibiramensis is a naturally rare, endemic and threatened bromeliad which occurs naturally on 4 km of rocky river outcroppings in Southern Brazil. For this study, subpopulations of the species were characterized based on size and genetics, to compile information for in situ and ex situ conservation strategies. A census of the rosettes was undertaken for each subpopulation and seven allozyme polymorphic loci were used to estimate genetic diversity and structure of adults and offspring and assess the mating system. In general, the subpopulations were small and most of the rosettes were aggregated into clumps. The species showed a high genetic diversity ([^(H)]_e = 0.219 \hat{H}_{e} = 0.219 ) and significant fixation index ([^(f)] = 0.642, \hat{f} = 0.642, P ≤ 0.05). The estimate of differentiation among all adult subpopulations indicate pronounced genetic structure ([^(G)]^￠_ST = 0.674 \hat{G}^{\prime}_{ST} = 0.674 ). D. ibiramensis has a mixed mating system and multilocus outcrossing rates [^(t)]_m \hat{t}_{m} were variable between subpopulations. This study demonstrates the importance of in situ preservation of all subpopulations for the maintenance of species diversity. For effective ex situ conservation, it would be necessary to collect seeds from 52 to 99 seed-rosettes, depending on the target population.     

The neuropeptide Gonadotropin-releasing hormone modifies the spontaneous muscular contraction in the earthworm: <Emphasis Type="Italic">Eisenia foetida</Emphasis>

We investigated whether the Gonadotropin-releasing hormone affects the spontaneous muscular contraction in the earthworm Eisenia foetida. In addition, we investigated the presence of Gonadotropin-releasing hormone receptor in ventral nerve cord by immunohistochemistry and polymerase chain reaction. Gonadotropin-releasing hormone induced a significant increase on both amplitude and muscular tone and decrease in the frequency of spontaneous muscular contraction. We found the presence of immunoreactive material to Gonadotropin-releasing hormone receptor in the ventral nerve cord, likewise the Gonadotropin-releasing hormone receptor mRNA expression. In conclusion, the Gonadotropin-releasing hormone modifies the spontaneous muscular contraction in E. foetida and these effects can be due to the activation of the Gonadotropin-releasing hormone receptor.     

Prevalence of the most frequent BRCA1 mutations in Polish population

The purpose of our study was to establish the frequency and distribution of the four most common BRCA1 mutations in Polish general population and in a series of breast cancer patients. Analysis of the population frequency of 5382insC (c.5266dupC), 300T >G (p.181T >G), 185delAG (c.68_69delAG) and 3819del5 (c.3700_3704del5) mutations of the BRCA1 gene were performed on a group of respectively 16,849, 13,462, 12,485 and 3923 anonymous samples collected at birth in seven Polish provinces. The patient group consisted of 1845 consecutive female breast cancer cases. The most frequent BRCA1 mutation in the general population was 5382insC found in 29 out of 16,849 samples (0.17%). 300T >G and 3819del5 mutations were found in respectively 11 of 13,462 (0.08%) and four of 3923 (0.1%) samples. The population prevalence for combined Polish founder 5382insC and 300T >G mutations was 0.25% (1/400). The frequencies of 5382insC and 300T >G carriers among consecutive breast cancer cases were, respectively, 1.9% (35/1845) and 1.2% (18/1486). Comparing these data with the population frequency, we calculated the relative risk of breast cancer for 5382insC mutation at OR = 17 and for 300T >G mutation at OR = 26. Our results, based on large population studies, show high frequencies of founder 5382insC and 300T >G BRCA1 mutations in Polish general population. Carriage of one of these mutations is connected with a very high relative risk of breast cancer.     

Exploitation of mitochondrial nad6 as a complementary marker for studying population variability in Lepidoptera

The applicability of mitochondrial nad6 sequences to studies of DNA and population variability in Lepidoptera was tested in four species of economically important moths and one of wild butterflies. The genetic information so obtained was compared to that of cox1 sequences for two species of Lepidoptera. nad6 primers appropriately amplified all the tested DNA targets, the generated data proving to be as informative and suitable in recovering population structures as that of cox1. The proposal is that, to obtain more robust results, this mitochondrial region can be complementarily used with other molecular sequences in studies of low level phylogeny and population genetics in Lepidoptera.