Transition metal-catalysed A-ring C–H activations and C(sp2)–C(sp2) couplings in the 13α-oestrone series and in vitro evaluation of antiproliferative properties

Facile syntheses of 3-O-carbamoyl, -sulfamoyl, or -pivaloyl derivatives of 13α-oestrone and its 17-deoxy counterpart have been carried out. Microwave-induced, Ni-catalysed Suzuki–Miyaura couplings of the newly synthesised phenol esters with phenylboronic acid afforded 3-deoxy-3-phenyl-13α-oestrone derivatives. The carbamate and pivalate esters proved to be suitable for regioselective arylations. 2-(4-Substituted) phenyl derivatives were synthesised via Pd-catalysed, microwave-assisted C–H activation reactions. An efficient, one-pot, tandem methodology was elaborated for the introduction of the carbamoyl or pivaloyl group followed by regioselective C-2-arylation and subsequent removal of the directing group. The antiproliferative properties of the novel 13α-oestrone derivatives were evaluated in vitro on five human adherent cancer cell lines of gynaecological origin. 3-Sulfamate derivatives displayed substantial cell growth inhibitory potential against certain cell lines. The newly identified antiproliferative compounds having hormonally inactive core might be promising candidates for the design of more active anticancer agents.     

SARS-CoV-2 S glycoprotein binding to multiple host receptors enables cell entry and infection

Glycoconjugate Journal - The severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) infection displays a wide array of clinical manifestations. Although some risk factors for...     

Impact of host plant quality on geometrid moth expansion on environmental and local population scales

The warming climate has enabled a rapid expansion of many forest pests. The adaptation potential of the invaders affects largely on how well the invasive species can spread to new areas and in what extent can they have an impact on the invaded ecosystem. To measure the adaptation potential of an invasive (winter moth) and a potentially invasive defoliating moth species (scarce umber moth), we examined life history parameters in two environments on a set of genetically diverse host trees and compared the traits with those of a resident moth species (autumnal moth). In addition, variations in life history parameters due to host genotype were calculated and compared. The bioassay was executed by rearing moth larvae on 11 half‐sib families of the host tree in two large tree line gardens. The use of half‐sib families allowed us to calculate the variances due to tree genotype and also to examine if the new arrivals can affect the selection pressure on the genetic population structure of the host. According to our results, the natural genetic variation in host plant quality and small environmental differences are not sufficiently effective to restrict the spread of the already established invasive species. The invading moth species may even be better at adapting to variation in food quality than the resident moth species. The overall effect of the natural variation in tree quality was similar for all three moth species. Therefore, the newcomers are likely to only inflict a quantitative rather than qualitative change in the selection pressure on the host.     

IGF-I and NEFA concentrations in fetal fluids of term pregnancy dogs

Insulin-like growth factor-I (IGF-I) and non-esterified fatty acids (NEFA) play an essential role in fetal growth and development. To date, fetal fluids IGF-I and NEFA levels at term canine pregnancy are unknown and could be related to the neonatal development and breed size. For these reasons, the aims of the present study were as follows: (1) to evaluate IGF-I and NEFA concentrations in fetal fluids collected from normally developed and viable newborn puppies born at term of normal pregnancies; (2) to assess possible differences between IGF-I and NEFA levels in amniotic compared with allantoic fluid; (3) to detect possible relationship between breed body size and IGF-I and NEFA amniotic and allantoic concentrations; (4) to evaluate possible differences in IGF-I fetal fluids levels between male and female puppies; and (5) to assess possible correlations between the two hormones in each type of fluid. The study enrolled 25 pure breed bitches submitted to elective Cesarean section at term because of the high risk of dystocia or previous troubles at parturition. At surgery, amniotic and allantoic fluids were collected and assayed for IGF-I and NEFA. IGF-I and NEFA amounts in both amniotic and allantoic fluids of different breed size bitches (small: ≤10 kg; medium: 11–25 kg; large: 26–40 kg) were detected, as well as the effect of gender on IGF-I levels. On a total of 73 amniotic and 76 allantoic samples collected by normal, viable, and mature newborns, the mean IGF-I concentration was significantly higher in amniotic than in allantoic fluid in all three groups, but the amniotic IGF-I levels were significantly lower in small and medium size bitches when compared with large ones. No significant differences were found in allantoic IGF-I concentrations among size groups. A significant effect of the puppy gender on IGF-I content in both fetal fluids was not reported. Regarding NEFA, in all the three groups, the mean NEFA concentration did not significantly differ between amnion and allantois, but in both fetal fluids, higher NEFA levels were detected in samples belonging to small breeds when compared with medium and large. These data strongly indicated that, also in the dog, a relation between fetal fluids IGF-I and NEFA concentrations and breed size exists. Further research is needed to elucidate the possible role of IGF-I and NEFA in the pathologic conditions related to canine fetal growth.     

There is no general model for occlusal kinematics in conodonts

Knowledge of conodont element function is based largely on analysis of morphologically similar P₁ elements of few comparatively closely related species known from abundant articulated remains. From these, a stereotypical pattern of rotational occlusion has been inferred, leading to the suggestion that this may represent a general model for ozarkodinin P₁ elements at the very least. We test the generality of this occlusal model through functional analysis of Pseudofurnishius murcianus P₁ elements which, though superficially similar to homologous elements in gnathodids, evolved their platform morphology independently, through a different mode of morphogenesis, and in a different topological position within the element. Our integrated functional analysis of several articulated clusters of P₁ elements encompassed physical and virtual occlusal analyses, constrained by microwear and sharpness analyses. All of the evidence supports an occlusal model in which the Pseudofurnishius P₁ elements occluded with the dextral blade located between the rostral face of the sinistral blade and the first cusp of the rostral primary process. In achieving this, the dorsal and ventral blades guided the opposing elements, and the rostral processes of both elements guided the final stages of precise occlusion. Spalling and microwear on the non‐occlusal side of the element evidence malocclusion, requiring the complete separation of elements within the occlusal cycle. This occlusal cycle is entirely linear, orthogonal to the plane of attachment of the elements. Evidently, the rotational occlusal model is not general for P₁ elements, even for ozarkodinins, and it is likely that among conodonts occlusal kinematics are as disparate as element morphologies. Attempts to elucidate the diversity of occlusal kinematics and, therefore, feeding ecologies of conodonts will be repaid by an understanding of the role of this important abundant and diverse clade in Palaeozoic and Mesozoic marine ecosystems.     

Genetic composition of the Jadro softmouth trout following translocation into a new habitat

Genetic founder effects of a historical translocation (1965; app. 12 generations ago) of endangered softmouth trout from the only remaining indigenous population to an adjacent uninhabited river were investigated. A comparison of 15 microsatellites from contemporary samples in both the source and re-established populations indicated a very low level of genetic diversity within the two populations. Furthermore, considerable differences in estimates of variability and effective population sizes were detected between populations, but no recent bottlenecks were evident. Our data suggest that the re-established population has lost variation due to genetic drift associated with founder effects following the translocation. Accordingly, in relation to management, we suggest that the re-established population could serve as a secondary source of individuals to buffer possible extinction due to demographic events. Finally, conservation initiatives to enhance the census population size and increase levels of variability in the re-established population are proposed. Electronic Supplementary Material Supplementary material is available in the online version of this article at and is accessible for authorized users.