Kretzoiarctos gen. nov., the Oldest Member of the Giant Panda Clade

The phylogenetic position of the giant panda, Ailuropoda melanoleuca (Carnivora: Ursidae: Ailuropodinae), has been one of the most hotly debated topics by mammalian biologists and paleontologists during the last century. Based on molecular data, it is currently recognized as a true ursid, sister-taxon of the remaining extant bears, from which it would have diverged by the Early Miocene. However, from a paleobiogeographic and chronological perspective, the origin of the giant panda lineage has remained elusive due to the scarcity of the available Miocene fossil record. Until recently, the genus Ailurarctos from the Late Miocene of China (ca. 8–7 mya) was recognized as the oldest undoubted member of the Ailuropodinae, suggesting that the panda lineage might have originated from an Ursavus ancestor. The role of the purported ailuropodine Agriarctos, from the Miocene of Europe, in the origins of this clade has been generally dismissed due to the paucity of the available material. Here, we describe a new ailuropodine genus, Kretzoiarctos gen. nov., based on remains from two Middle Miocene (ca. 12–11 Ma) Spanish localities. A cladistic analysis of fossil and extant members of the Ursoidea confirms the inclusion of the new genus into the Ailuropodinae. Moreover, Kretzoiarctos precedes in time the previously-known, Late Miocene members of the giant panda clade from Eurasia (Agriarctos and Ailurarctos). The former can be therefore considered the oldest recorded member of the giant panda lineage, which has significant implications for understanding the origins of this clade from a paleobiogeographic viewpoint

Monitoring integrity and localization of modified single-stranded RNA oligonucleotides using ultrasensitive fluorescence methods

Short single-stranded oligonucleotides represent a class of promising therapeutics with diverse application areas. Antisense oligonucleotides, for example, can interfere with various processes involved in mRNA processing through complementary base pairing. Also RNA interference can be regulated by antagomirs, single-stranded siRNA and single-stranded microRNA mimics. The increased susceptibility to nucleolytic degradation of unpaired RNAs can be counteracted by chemical modification of the sugar phosphate backbone. In order to understand the dynamics of such single-stranded RNAs, we investigated their fate after exposure to cellular environment by several fluorescence spectroscopy techniques. First, we elucidated the degradation of four differently modified, dual-dye labeled short RNA oligonucleotides in HeLa cell extracts by fluorescence correlation spectroscopy, fluorescence cross-correlation spectroscopy and Forster resonance energy transfer. We observed that the integrity of the oligonucleotide sequence correlates with the extent of chemical modifications. Furthermore, the data showed that nucleolytic degradation can only be distinguished from unspecific effects like aggregation, association with cellular proteins, or intramolecular dynamics when considering multiple measurement and analysis approaches. We also investigated the localization and integrity of the four modified oligonucleotides in cultured HeLa cells using fluorescence lifetime imaging microscopy. No intracellular accumulation could be observed for unmodified oligonucleotides, while completely stabilized oligonucleotides showed strong accumulation within HeLa cells with no changes in fluorescence lifetime over 24 h. The integrity and accumulation of partly modified oligonucleotides was in accordance with their extent of modification. In highly fluorescent cells, the oligonucleotides were transported to the nucleus. The lifetime of the RNA in the cells could be explained by a balance between release of the oligonucleotides from endosomes, degradation by RNases and subsequent depletion from the cells

Ash from the Toba supereruption in Lake Malawi shows no volcanic winter in East Africa at 75 ka

The most explosive volcanic event of the Quaternary was the eruption of Mt. Toba, Sumatra, 75,000 y ago, which produced voluminous ash deposits found across much of the Indian Ocean, Indian Peninsula, and South China Sea. A major climatic downturn observed within the Greenland ice cores has been attributed to the cooling effects of the ash and aerosols ejected during the eruption of the Youngest Toba Tuff (YTT). These events coincided roughly with a hypothesized human genetic bottleneck, when the number of our species in Africa may have been reduced to near extinction. Some have speculated that the demise of early modern humans at that time was due in part to a dramatic climate shift triggered by the supereruption. Others have argued that environmental conditions would not have been so severe to have such an impact on our ancestors, and furthermore, that modern humans may have already expanded beyond Africa by this time. We report an observation of the YTT in Africa, recovered as a cryptotephra layer in Lake Malawi sediments, >7,000 km west of the source volcano. The YTT isochron provides an accurate and precise age estimate for the Lake Malawi paleoclimate record, which revises the chronology of past climatic events in East Africa. The YTT in Lake Malawi is not accompanied by a major change in sediment composition or evidence for substantial temperature change, implying that the eruption did not significantly impact the climate of East Africa and was not the cause of a human genetic bottleneck at that time

Successful programs wanted: exploring the impact of alignment.

Alignment between formulation and implementation of business strategy can be important for achieving successful programmes. The authors have explored developing a programme management alignment theory. Statistical testing suggests that interaction between the study model variables was found to be multidimensional, complex and subtle in influence. They conclude that programmes have both deliberate and emergent strategies requiring design and management to be organised as complex adaptive systems. Programme lifecycle phases of design and transition were often illustrated by an unclear and confusing strategic picture at the outset which makes it difficult to control. Learning was established as an underlying challenge. The study model demonstrated continuous alignment as an essential attribute contributing towards successful delivery. This requires programme design and structure to adopt an adaptive posture