Interferon and Interferon Inducers in the Treatment of Malignancies

The mechanism of the antitumor action of polyinosinic-polycytidylic acid is probably multifaceted. The compound induces the synthesis of interferon, and interferon probably is active against some tumors. Poly I:poly C alters protein and RNA synthesis in tissue culture. It specifically inhibits such macromolecule synthesis in tumors in vivo, while having less inhibitory action on synthesis in normal organs, or it may actually enhance. Finally, poly I:poly C strongly enhances graft vs. host rejection mechanisms, which may play a role in the rejection of some tumors.     

Combined loss of Cdk2 and Cdk4 results in embryonic lethality and Rb hypophosphorylation

Mouse knockouts of Cdk2 and Cdk4 have demonstrated that, individually, these genes are not essential for viability. To investigate whether there is functional redundancy, we have generated double knockout (DKO) mice. Cdk2-/- Cdk4-/- DKOs die during embryogenesis around E15 as a result of heart defects. We observed a gradual decrease of Retinoblastoma protein (Rb) phosphorylation and reduced expression of E2F-target genes, like Cdc2 and cyclin A2, during embryogenesis and in embryonic fibroblasts (MEFs). DKO MEFs are characterized by a decreased proliferation rate, impaired S phase entry, and premature senescence. HPV-E7-mediated inactivation of Rb restored normal expression of E2F-inducible genes, senescence, and proliferation in DKO MEFs. In contrast, loss of p27 did not rescue Cdk2-/- Cdk4-/- phenotypes. Our results demonstrate that Cdk2 and Cdk4 cooperate to phosphorylate Rb in vivo and to couple the G1/S phase transition to mitosis via E2F-dependent regulation of gene expression.     

Throwing the baby out with the bathwater: does laurel forest restoration remove a critical winter food supply for the critically endangered Azores bullfinch?

The invasive Clethra arborea has a dual-role in the diet of the Azores bullfinch, a critically endangered bird species endemic to the island of São Miguel (Azores, Portugal). This is a crucial winter food resource but it lowers the availability of native laurel forest species that compose most of the bird’s diet throughout the year. The removal of this and other invasive alien species is part of current laurel forest habitat restoration programmes, disregarding the impact on the Azores bullfinch population. In order to evaluate the first responses of the Azores bullfinch to habitat restoration, we studied bird diet, foraging behaviour, food availability and habitat occupancy in managed (without C. arborea) and control areas. Significant increases in the availability of native food resources in managed areas were noticeable in the diet, particularly the intake of Ilex perado ssp. azorica and Prunus lusitanica ssp. azorica flower buds. In most of the studied months birds heavily used and foraged in managed over control areas. The one exception was in December, when a resource-gap occurred in managed areas, which may be overcome in the short-term due to re-establishment of native plants following removal of invasive aliens.     

Re-evaluation of Halle’s fertile pteridosperms from the Permian floras of Shanxi Province, China

In 1927, T. G. Halle published an extensive synthesis of the Permian fossil plant assemblages from China’s Shanxi Province that included five genera and species of seed plant that either had ovules in organic attachment or closely and repeatedly associated with foliage. These fertile pteridosperms were the subject of a later publication (1929) that provided additional information on each species, but since that time only Nystroemia pectiniformis Halle has been subjected to detailed investigation based on the original materials. Reinvestigation of the remaining four species has yielded additional examples and new information for each species, and has confirmed the pteridospermalean affinity for three of the four species. Alethopteris norinii Halle shows organic attachment of a pollen organ similar to Wittleseya (Newberry) Halle and is reinterpreted as a microsporangiate medullosan pteridosperm. Emplectopteris triangularis Halle and Sphenopteris tenuis (Schenk) Halle both bear numerous ovules attached directly to the leaf laminae, with Emplectopteris conforming with the gross-organisation of callistophytalean pteridosperms and S. tenuis being interpreted as a derived lagenostomalean pteridosperm. However, discovery of the counterpart to the key specimen of Pecopteris wongii Halle that Halle interpreted as bearing ovules demonstrates this species to be a sterile marattialean frond that agrees with its assignment to Pecopteris. In addition, two further specimens are demonstrated to be fertile organs of previously unknown pteridosperms; Norinosperma shanxiensis gen. et sp. nov. bears cardiocarpalean ovules abaxially on the proximal portions of the frond with ovules positioned directly on the veins of a leaf lamina; Norinotheca shanxiensis gen. et sp. nov. bears large pollen organs abaxially and singly on the vein of the leaf lamina. Collectively Halle’s pteridosperms remain important today as they are some of the few specimens that actually demonstrate organic connection of fertile organs to foliage, helping to characterise the morphology and organisation of this seed plant group. These species also demonstrate the persistence of seed plant families and genera in the Permian of China that became regionally extinct at the end of the Carboniferous in Euramerica, and show that pteridosperms remained an important component of Permian as well as Carboniferous floras globally.     

Species-Specific Functions of Twinfilin in Actin Filament Depolymerization

Twinfilin is a highly conserved member of the actin depolymerization factor homology (ADF-H) protein superfamily, which also includes ADF/Cofilin, Abp1/Drebrin, GMF, and Coactosin. Twinfilin has a unique molecular architecture consisting of two ADF-H domains joined by a linker and followed by a C-terminal tail. Yeast Twinfilin, in conjunction with yeast cyclase-associated protein (Srv2/CAP), increases the rate of depolymerization at both the barbed and pointed ends of actin filaments. However, it has remained unclear whether these activities extend to Twinfilin homologs in other species. To address this, we purified the three mouse Twinfilin isoforms (mTwf1, mTwf2a, mTwf2b) and mouse CAP1, and used total internal reflection fluorescence microscopy assays to study their effects on filament disassembly. Our results show that all three mouse Twinfilin isoforms accelerate barbed end depolymerization similar to yeast Twinfilin, suggesting that this activity is evolutionarily conserved. In striking contrast, mouse Twinfilin isoforms and CAP1 failed to induce rapid pointed end depolymerization. Using chimeras, we show that the yeast-specific pointed end depolymerization activity is specified by the C-terminal ADF-H domain of yeast Twinfilin. In addition, Tropomyosin decoration of filaments failed to impede depolymerization by yeast and mouse Twinfilin and Srv2/CAP, but inhibited Cofilin severing. Together, our results indicate that Twinfilin has conserved functions in regulating barbed end dynamics, although its ability to drive rapid pointed end depolymerization appears to be species-specific. We discuss the implications of this work, including that pointed end depolymerization may be catalyzed by different ADF-H family members in different species.