The oldest mysticete in the Northern Hemisphere.

Extant baleen whales (Mysticeti) uniquely use keratinous baleen for filter-feeding and lack dentition, but the fossil record clearly shows that "toothed" baleen whales first appeared in the Late Eocene.1 Globally, only two Eocene mysticetes have been found, and both are from the Southern Hemisphere: Mystacodon selenensis from Peru, 36.4 mega-annum (Ma) ago1,2 and Llanocetus denticrenatus from Antarctica, 34.2 Ma ago.3,4 Based on a partial skull from the lower part of the Lincoln Creek Formation in Washington State, USA, we describe the Northern Hemisphere's geochronologically earliest mysticete, Fucaia humilis sp. nov. Geology, biostratigraphy, and magnetostratigraphy places Fucaia humilis sp. nov. in the latest Eocene (ca. 34.5 Ma ago, near the Eocene/Oligocene transition at 33.9 Ma ago), approximately coeval with the oldest record of fossil kelps, also in the northeastern Pacific.5 This observation leads to our hypothesis that the origin and development of a relatively stable, nutrient-rich kelp ecosystem5,6 in the latest Eocene may have fostered the radiation of small-sized toothed mysticetes (Family Aetiocetidae) in the North Pacific basin, a stark contrast to the larger Llanocetidae (whether Mystacodon belongs to llanocetids or another independent clade remains unresolved) with the latest Eocene onset of the Antarctic Circumpolar Current in the Southern Hemisphere.7,8,9 Our discovery suggests that disparate mechanisms and ecological scenarios may have nurtured contrasting early mysticete evolutionary histories in the Northern and Southern hemispheres.

Dwarfism and gigantism drive human-mediated extinctions on islands.

Islands have long been recognized as distinctive evolutionary arenas leading to morphologically divergent species, such as dwarfs and giants. We assessed how body size evolution in island mammals may have exacerbated their vulnerability, as well as how human arrival has contributed to their past and ongoing extinctions, by integrating data on 1231 extant and 350 extinct species from islands and paleo islands worldwide spanning the past 23 million years. We found that the likelihood of extinction and of endangerment are highest in the most extreme island dwarfs and giants. Extinction risk of insular mammals was compounded by the arrival of modern humans, which accelerated extinction rates more than 10-fold, resulting in an almost complete demise of these iconic marvels of island evolution.

Taxonomic revision of Chinemys pani (Testudines: Geoemydidae) from the Pleistocene of Taiwan and its implications of conservation paleobiology.

Proper taxonomic identification is critical to our understanding of biodiversity and the underlying evolutionary history. Here we re-examine the cast of the holotype of Chinemys pani, a geoemydid turtle from the Pleistocene of Taiwan; the actual specimen was not curated appropriately after the original publication and was most likely lost. Our results provide substantial evidence to show that Chinemys pani should be identified as Mauremys reevesii. The replica, though not ideal, preserves various morphological features that allow reliable taxonomic identification of Mauremys reevesii, including the presence of three longitudinal keels on the carapace, the second to sixth neural bones anteriorly short-sided, and the lack of a movable plastral hinge. In addition, we also confirm that the original diagnostic features that established the new taxon: Chinemys pani - are polymorphic characters of Mauremys reevesii. Our taxonomic revision of a Pleistocene geoemydid turtle from Taiwan confirms the existence of the Pleistocene Mauremys reevesii. More importantly, this study offers new insights into the origin of modern biodiversity in Taiwan and gives a straightforward example of how fossils can be applied to conservation policies.

Inhibition of Heat Shock Protein 90 suppresses TWIST1 Transcription.

Molecular chaperone heat shock protein 90 (HSP90) is involved in oncogenic signaling pathways including epithelial-mesenchymal transition (EMT), a key process in tumor initiation, progression, metastasis, and chemoresistance. The molecular mechanisms underlying the involvement of HSP90 in EMT are still under investigation. In this study, we identified a previously unrecognized role of HSP90 in cooperating with signal transducer and activator of transcription 3 (STAT3) to regulate TWIST1 transcription in cancer cells. The HSP90 inhibitor 17-N-allylamino-17-demethoxygeldanamycin suppressed TWIST1 mRNA expression and promoter activity in epithelial ovarian cancer, renal clear cell cancer, and nasopharyngeal cancer cell lines. The interactions between HSP90 and transcription factors were visualized in cancer cell lines and tumor tissues using proximity ligation assays. Our findings reveal that HSP90 promotes the binding of STAT3 to the TWIST1 promoter, leading to the transcription of TWIST1. The inhibition of HSP90 downregulates STAT3 activity and TWIST1 transcription, thereby suppressing EMT and potentially inhibiting tumor progression, metastasis, and chemoresistance in different types of cancers. SIGNIFICANCE STATEMENT: Our study provides new evidence that HSP90 promotes EMT through enhancing TWIST1 transcription, which can be suppressed by HSP90 inhibitors. The HSP90 inhibitor inhibits EMT, thus potentially slowing down tumor growth, invasion, dissemination, metastasis, and drug resistance. These findings will hopefully pave the way for new therapeutic opportunities to target EMT and metastasis using HSP90 inhibitors.

A right whale (Mysticeti, Balaenidae) from the Pleistocene of Taiwan.

Current patterns of biological distribution result from the deep past. Of particular interest, some closely related species appear at high latitudes of both hemispheres, but not in between, a pattern known as antitropical distribution. However, the timing, pathway, and drivers of antitropical distributions remain mostly unknown. Here we describe a new fossil, a left tympanic bulla (part of the ear bones), from the Middle/Late Pleistocene (0.78-0.01 mya, but not excluding the possibility of Holocene in age, as the specimen was dredged from the sea bottom and the geological horizon remains uncertain) of Taiwan. The tympanic bulla is diagnostic in baleen whales, and this specimen shows morphological features that are identical to extant Eubalaena, including: relatively large size (the anteroposterior length is 117 mm); rectangular outline in medial view; short anterior lobe, judging from the remaining of the lateral furrow; squared anterior margin; prominent transverse crease on the involucrum; transversely compressed in anterior view; well-developed and rounded outer lip; and parallel involucral and main ridges. Although incomplete, the morphological characters and overall similarity to extant Eubalaena allow a reliable taxonomic assignment to Eubalaena sp. The occurrence of a Pleistocene Eubalaena on the southern margin of the western North Pacific is the first balaenid fossil evidence indicative of the biotic interchange between two hemispheres leading to the origin of antitropical distribution in the Pleistocene; alternatively, this specimen might merely represent an extra-limital record of the North Pacific Eubalaena. Furthermore, this find suggests that the Eubalaena interchange, being one of the largest species displaying antitropical distribution pairs in the history of life, likely took place along the western Pacific. Notably, this does not preclude the Eubalaena interchange from other routes, such as the eastern Pacific or the Atlantic Ocean, and future finds should test the scenario for the biotic interchange between Northern and Southern Hemispheres of Eubalaena.

Crossing the equator: a northern occurrence of the pygmy right whale.

Here we document the first stranding record of the pygmy right whale in the Northern Hemisphere-on the coast of The Gambia, Africa (NE Atlantic Ocean, around latitude 13° N)-a location in stark contrast to its current distribution exclusively south of the equator. The original specimen is now missing and untraceable, but a photo found in the files of the Marine Mammal Program, Smithsonian Institution shows sufficient diagnostic features that allow it to be taxonomically identified as the pygmy right whale, Caperea marginata, including: small body size; streamlined overall body shape; generally dark skin coloration; arched rostrum along the lateral margin; triangular and narrow rostrum in dorsal view; lack of head callosities; some fringes on the dorsal surface of the tongue; small and relatively posteriorly positioned dorsal fin; and small and dark-colored flipper. On the whole, a stranding of the pygmy right whale in the Northern Hemisphere, although likely to be a chance event, calls for more detailed studies of how climate change and ocean currents affect the evolution and distribution (re-patterning) of marine mammals and, ultimately, the entire marine ecosystem.

A new archaic baleen whale Toipahautea waitaki (early Late Oligocene, New Zealand) and the origins of crown Mysticeti.

A new genus and species of extinct baleen whale †Toipahautea waitaki (Late Oligocene, New Zealand) is based on a skull and associated bones, from the lower Kokoamu Greensand, about 27.5 Ma (local upper Whaingaroan Stage, early Chattian). The upper jaw includes a thin, elongate and apparently toothless maxilla, with evidence of arterial supply for baleen. Open sutures with the premaxilla suggest a flexible (kinetic) upper jaw. The blowhole is well forward. The mandible is bowed laterally and slightly dorsally; unlike the Eomysticetidae, there are no mandibular alveoli, and the coronoid process is tapered and curved laterally. Jaw structure is consistent with baleen-assisted gulp-feeding. The age of early Chattian makes †Toipahautea a very early, if not the oldest named, toothless and baleen-bearing mysticete, suggesting that the full transition from toothed to baleen-bearing probably occurred in the Early Oligocene. Late Oligocene mysticetes vary considerably in jaw form and kinesis, tooth form and function, and development of baleen, implying a wide range of raptorial, suctorial and filter-feeding behaviour. More study may elucidate the function of jaws, teeth and baleen in terms of opportunist/generalist feeding, as in modern gray whales, versus specialized feeding. We here propose that early mysticetes, when transitioned from toothed to baleen-bearing, were generalists and opportunists instead of specializing in any forms of feeding strategies. In addition, two different phylogenetic analyses placed †Toipahautea either in a polytomy including crown Mysticeti, or immediately basal to the crown, and above †Eomysticetidae in both cases. Because the †Toipahautea waitaki holotype is an immature individual, it may plot more basally in phylogeny than its true position.

Northern pygmy right whales highlight Quaternary marine mammal interchange.

The pygmy right whale, Caperea marginata, is the most enigmatic living whale. Little is known about its ecology and behaviour, but unusual specialisations of visual pigments [1], mitochondrial tRNAs [2], and postcranial anatomy [3] suggest a lifestyle different from that of other extant whales. Geographically, Caperea represents the only major baleen whale lineage entirely restricted to the Southern Ocean. Caperea-like fossils, the oldest of which date to the Late Miocene, are exceedingly rare and likewise limited to the Southern Hemisphere [4], despite a more substantial history of fossil sampling north of the equator. Two new Pleistocene fossils now provide unexpected evidence of a brief and relatively recent period in geological history when Caperea occurred in the Northern Hemisphere (Figure 1A,B).

A Miocene breeding ground of an extinct baleen whale (Cetacea: Mysticeti).

Locating breeding sites is definitely a key to understanding the ecological requirements and maintaining the sustainability of populations/species. Here I re-examined published specimens of an extinct baleen whale, Parietobalaena yamaokai, from the lower part of Itahashi Formation (16.1-15.6 Ma, Middle Miocene) in Shobara, Hiroshima, Japan. A critical and previously unnoticed feature, the open suture between the supraoccipital and exoccipital, in one specimen indicates the preservation of a very young individual-under six months old and even close to a new-born calf. Given the occurrence of a new-born whale and relatively abundant assemblage of Parietobalaena yamaokai, I propose a previously hidden and unknown breeding ground for the extinct baleen whale, P. yamaokai, in the Middle Miocene of Shobara (16.1-15.6 Ma), Hiroshima. Discovery of paleo-breeding sites of extinct populations/species should further help us to understand biological extinctions from a long-term perspective as conservation paleobiology aims to offer new insights into policy making for conserving endangered populations/species.

Multiple origins of gigantism in stem baleen whales.

Living baleen whales (Mysticeti) include the world's largest animals to have ever lived-blue whales (Balaenoptera musculus) can reach more than 30 m. However, the gigantism in baleen whales remains little explored. Here, we compiled all published stem mysticetes from the Eocene and Oligocene and then mapped the estimated body size onto different phylogenies that suggest distinct evolutionary histories of baleen whales. By assembling all known stem baleen whales, we present three novel findings in early mysticete evolution. Results show that, regardless of different phylogenetic scenarios, large body size (more than 5-m long) evolved multiple times independently in their early evolutionary history. For example, the earliest known aetiocetid (Fucaia buelli, 33-31 Ma) was small in size, about 2 m, and a later aetiocetid (Morawanocetus-like animal, 26-23 Ma) can reach 8-m long-almost four times the size of Fucaia buelli-suggesting an independent gigantism in the aetiocetid lineage. In addition, our reconstruction of ancestral state demonstrates that the baleen whales originated from small body size (less than 5 m) rather than large body size as previously acknowledged. Moreover, reconstructing the evolution of body size in stem baleen whales suggests that the initial pulse of mysticete gigantism started at least back to the Paleogene and in turn should help to understand the origin, pattern, and process of the extreme gigantism in the crown baleen whales. This study illustrates that Cope's rule is insufficient to explain the evolution of body size in a group that comprises the largest animals in the history of life, although currently the lack of exact ancestor-descendant relationships remains to fully reveal the evolutionary history of body size.

Ancestor-descendant relationships in evolution: origin of the extant pygmy right whale, Caperea marginata.

Ancestor-descendant relationships (ADRs), involving descent with modification, are the fundamental concept in evolution, but are usually difficult to recognize. We examined the cladistic relationship between the only reported fossil pygmy right whale, †Miocaperea pulchra, and its sole living relative, the enigmatic pygmy right whale Caperea marginata, the latter represented by both adult and juvenile specimens. †Miocaperea is phylogenetically bracketed between juvenile and adult Caperea marginata in morphologically based analyses, thus suggesting a possible ADR-the first so far identified within baleen whales (Cetacea: Mysticeti). The †Miocaperea-Caperea lineage may show long-term morphological stasis and, in turn, punctuated equilibrium.

A new Early Oligocene toothed 'baleen' whale (Mysticeti: Aetiocetidae) from western North America: one of the oldest and the smallest.

Archaic toothed mysticetes represent the evolutionary transition from raptorial to bulk filter feeding in baleen whales. Aetiocetids, in particular, preserve an intermediate morphological stage in which teeth functioned alongside a precursor of baleen, the hallmark of all modern mysticetes. To date, however, aetiocetids are almost exclusively Late Oligocene and coeval with both other toothed mysticetes and fully fledged filter feeders. By contrast, reports of cetaceans from the Early Oligocene remain rare, leaving the origins of aetiocetids, and thus of baleen, largely in the dark. Here, we report a new aetiocetid, Fucaia buelli, from the earliest Oligocene (ca 33-31 Ma) of western North America. The new material narrows the temporal gap between aetiocetids and the oldest known mysticete, Llanocetus (ca 34 Ma). The specimen preserves abundant morphological detail relating to the phylogenetically informative ear bones (otherwise poorly documented in this family), the hyoid apparatus and much of the (heterodont) dentition. Fucaia comprises some of the smallest known mysticetes, comparable in size with the smallest odontocetes. Based on their phylogenetic relationships and dental and mandibular morphology, including tooth wear patterns, we propose that aetiocetids were suction-assisted raptorial feeders and interpret this strategy as a crucial, intermediary step, enabling the transition from raptorial to filter feeding. Following this line of argument, a combination of raptorial and suction feeding would have been ancestral to all toothed mysticetes, and possibly even baleen whales as a whole.

Juvenile morphology in baleen whale phylogeny.

Phylogenetic reconstructions are sensitive to the influence of ontogeny on morphology. Here, we use foetal/neonatal specimens of known species of living baleen whales (Cetacea: Mysticeti) to show how juvenile morphology of extant species affects phylogenetic placement of the species. In one clade (sei whale, Balaenopteridae), the juvenile is distant from the usual phylogenetic position of adults, but in the other clade (pygmy right whale, Cetotheriidae), the juvenile is close to the adult. Different heterochronic processes at work in the studied species have different influences on juvenile morphology and on phylogenetic placement. This study helps to understand the relationship between evolutionary processes and phylogenetic patterns in baleen whale evolution and, more in general, between phylogeny and ontogeny; likewise, this study provides a proxy how to interpret the phylogeny when fossils that are immature individuals are included. Juvenile individuals in the peramorphic acceleration clades would produce misleading phylogenies, whereas juvenile individuals in the paedomorphic neoteny clades should still provide reliable phylogenetic signals.

SATB2 participates in regulation of menadione-induced apoptotic insults to osteoblasts.

Special AT-rich sequence binding protein 2 (SATB2), a nuclear matrix attachment region-binding protein, can regulate embryonic development, cell differentiation, and cell survival. Previous studies showed that SATB2 is involved in osteoblast differentiation and skeletal development. In this study, we evaluated the role of SATB2 in oxidative stress-induced apoptotic insults to human osteoblast-like MG63 cells and mouse MC3T3-E1 cells. Exposure of MG63 cells to menadione increased intracellular reactive oxygen species levels in a concentration- and time-dependent manner. Simultaneously, menadione-induced oxidative stress triggered cell shrinkage and decreased cell viability. In addition, treatment of MG63 cells with menadione time-dependently decreased the mitochondrial membrane potential but enhanced caspase-3 activity. As a result, menadione-induced DNA fragmentation and cell apoptosis. As to the mechanism, exposure of MG63 cells to menadione amplified SATB2 messenger (m)RNA and protein expression in a time-dependent manner. Knockdown of translation of SATB2 mRNA using RNA interference led to chromatin disruption and nuclear damage. When MG63 cells and MC3T3-E1 cells were treated with SATB2 small interfering RNA, menadione-induced cell apoptosis was increased. We conclude that menadione causes oxidative stress in human osteoblasts and induces cellular apoptosis via a mitochondrion-caspase protease pathway. In addition, SATB2 may play a crucial role in protecting against oxidative stress-induced osteoblast apoptosis.

Toll-like receptor 2-mediated sequential activation of MyD88 and MAPKs contributes to lipopolysaccharide-induced sp-a gene expression in human alveolar epithelial cells.

Surfactant proteins (SPs) produced by pulmonary epithelial cells participate in the regulation of sepsis-induced acute lung injury. Our previous study has shown that lipopolysaccharide (LPS), a Gram-negative bacterial outer membrane component, can regulate sp-a gene expression in human lung carcinoma type II epithelial A549 cells. This study was further designed to evaluate the signal-transducing mechanisms of LPS-induced sp-a gene expression. Exposure of A549 cells to LPS induced SP-A mRNA and protein production in time-dependent manners. Application of toll-like receptor 2 (TLR2) siRNA into A549 cells decreased the levels of this receptor and simultaneously inhibited LPS-induced SP-A mRNA expression. Sequentially, LPS enhanced phosphorylation of mitogen-activated protein kinase (MEK) 4 and c-Jun NH(2) terminal kinase 1 (JNK1) in time-dependent manners. Application of TLR2 siRNA decreased LPS-enhanced phosphorylation of MEK4 and JNK1. After knocking-down the translation of MyD88 by RNA interference, the LPS-triggered MEK4 phosphorylation was attenuated. Consequently, LPS augmented the translocation of c-Jun from the cytoplasm to nuclei without affecting c-Fos. Pretreatment of A549 cells with SP600125, an inhibitor of JNK1, significantly lowered LPS-induced SP-A mRNA production. Analyses of an electrophoretic mobility shift assay and a reporter gene further showed that LPS increased the transactivation activity of AP-1 in A549 cells. Therefore, the present study demonstrates that LPS can induce sp-a gene expression in human type II epithelial A549 cells through TLR2-mediated sequential activation of MyD88-MEK4-JNK1-AP-1.