Post-hatching growth of the limbs in an altricial bird species.

The fore- and hindlimbs of birds are specialized to perform different functions. The growth patterns of limb bones and their relationship with the ontogeny of locomotion are critical to our understanding of variation in morphological, physiological and life-history traits within and among species. Unfortunately, the ontogenetic development of limb bones has not been well explored, especially in altricial birds. In this study, we sampled the entire measurements of the pigeon (Columba livia) of individual skeletons, to investigate the ontogenetic allometry of limb bones by reduced major axis regression. The ulna and humerus were found to be positively allometric in relation to body mass, with the ulna growing more rapidly than the humerus. Together with previous data, this suggests that strong positive allometric growth in forelimb bones could be a common trend among diverse Carinatae groups. Hindlimb was dominated by positive allometry, but was variable in the growth of the tarsometatarsus which included three allometric patterns. A greater dorsoventral diameter in the midsection of the humerus and ulna confers superior bending resistance and is ideal for flapping/gliding flight. Shape variation in the midsection of different hindlimb components reflects different mechanical loading, and the markedly inverse trend between the tibiotarsus and tarsometatarsus before 28 days of age also suggests loading change before fledging. Before fledging, the growth of the leg bones was prior to that of the wing bones. This kind of asynchronous development of the fore- and hindlimbs was associated with the establishment and improvement of different functions, and with shifts in the importance of different functions over time.

ZC3H13 Inhibits the Progression of Hepatocellular Carcinoma through m6A-PKM2-Mediated Glycolysis and Enhances Chemosensitivity.

OBJECTIVE: N6-Methyladenosine (m6A) is the most prevalent RNA epigenetic modulation in eukaryotic cells, which serves a critical role in diverse physiological processes. Emerging evidences indicate the prognostic significance of m6A regulator ZC3H13 in hepatocellular carcinoma (HCC). Herein, this study was conducted for revealing biological functions and mechanisms of ZC3H13 in HCC. METHODS: Expression of ZC3H13 was examined in collected HCC and normal tissues, and its prognostic significance was investigated in a public database. Gain/loss of functional assays were presented for defining the roles of ZC3H13 in HCC progression. The specific interactions of ZC3H13 with PKM2 were validated in HCC cells via mRNA stability, RNA immunoprecipitation, and luciferase reporter and MeRIP-qPCR assays. Moreover, rescue experiments were carried out for uncovering the mechanisms. RESULTS: ZC3H13 expression was downregulated in HCC, and its loss was in relation to dismal survival outcomes. Functionally, overexpressed ZC3H13 suppressed proliferation, migration, and invasion and elevated apoptotic levels of HCC cells. Moreover, ZC3H13 overexpression sensitized to cisplatin and weakened metabolism reprogramming of HCC cells. Mechanically, ZC3H13-induced m6A modified patterns substantially abolished PKM2 mRNA stability. ZC3H13 facilitated malignant behaviors of HCC cells through PKM2-dependent glycolytic signaling. CONCLUSION: Collectively, ZC3H13 suppressed the progression of HCC through m6A-PKM2-mediated glycolysis and sensitized HCC cells to cisplatin, which offered a fresh insight into HCC therapy.