Sex-biased natal dispersal in Hokkaido brown bears revealed through mitochondrial DNA analysis

Understanding natal dispersal patterns is fundamental in the ecology and conservation biology of large wild carnivores. In this study, we used two approaches to determine genetic variation and dispersal patterns of brown bears in the Shiretoko Peninsula, eastern Hokkaido, Japan. The first approach was a large-scale genetic analysis. We analyzed haplotypes from the mitochondrial DNA (mtDNA) control region of 760 individual samples collected throughout the peninsula during 1998–2016. We detected seven haplotypes, including two that were confirmed for the first time. In females, the distribution of haplotypes was geographically structured, whereas haplotypes in males were distributed widely throughout the peninsula. Only some males in the lower peninsula had haplotypes that were not detected within the peninsula. The second approach was a local-scale genetic analysis, including intensive focal sampling in the Rusha area, a special wildlife protection area on the peninsula. Proportions of mtDNA haplotypes in adult bears were investigated and compared between the sexes. Although more than half of the females had the same haplotype, males had more diverse haplotypes, suggesting that they came to the Rusha area from other regions. Thus, our study revealed that mtDNA haplotype distribution has been maintained by female philopatry, and that bears exhibit male-biased dispersal. Furthermore, the lower peninsula appears to act as a contact zone between the peninsula and mainland Hokkaido, which is important for maintaining genetic diversity.     

Roles of collagen and periostin expression by cranial neural crest cells during soft palate development

The tissue in the palatal region can be divided into the hard and the soft palates, each having a specialized function such as occlusion, speech, or swallowing. Therefore, an understanding of the mechanism of palatogenesis in relation to the function of each region is important. However, in comparison with the hard palate, there is still a lack of information about the mechanisms of soft palate development. In this study, the authors investigated the contribution of cranial neural crest (CNC) cells to development of both hard and soft palates. They also demonstrated a unique pattern of periostin expression during soft palate development, which was closely related to that of collagen type I (Col I) in palatine aponeurosis. Furthermore, organ culture analysis showed that exogenous transforming growth factor-β (TGF-β) induced the expression of both periostin and Col I. These novel patterns of expression in the extracellular matrix (ECM) induced by CNC cells suggest that these cells may help to determine the character of both the hard and soft palates through ECM induction. TGF-β signaling appears to be one of the mediators of Col I and periostin expression in the formation of functional structures during soft palate development.     

Spatial localizations of Mam22 and Mam12 in the magnetosomes of Magnetospirillum magnetotacticum

Magnetospirillum magnetotacticum possesses intracellular magnetite particles with a chain-like structure, termed magnetosomes. The bacterium expresses 22-kDa and 12-kDa magnetosome-associated proteins, termed Mam22 (MamA) and Mam12 (MamC), respectively. In this study, we investigated the structure of the purified magnetosomes with transmission electron microscopic techniques and found that the magnetosomes consisted of four compartments, i.e., magnetite crystal, magnetosomal membrane, interparticle connection, and magnetosomal matrix. Furthermore, we determined the precise localizations of Mam22 and Mam12 using immunogold staining of the purified magnetosomes and ultrathin sections of the bacterial cells. Interestingly, most Mam22 existed in the magnetosomal matrix, whereas Mam12 was strictly localized in the magnetosomal membrane. Moreover, the recombinant Mam22 was attached to the magnetosomal matrix of the Mam22-deficient magnetosomes prepared by alkaline treatment, such as 0.1 M Caps-NaOH buffer (pH 11.0). The spatial localization of the magnetosome-associated proteins in the magnetosomal chain provides useful information to elucidate the functional roles of these proteins.     

A neural circuit model of emotional learning using two pathways with different granularity and speed of information processing

We propose a neural circuit model of emotional learning using two pathways with different granularity and speed of information processing. In order to derive a precise time process, we utilized a spiking model neuron proposed by Izhikevich and spike-timing-dependent synaptic plasticity (STDP) of both excitatory and inhibitory synapses. We conducted computer simulations to evaluate the proposed model. We demonstrate some aspects of emotional learning from the perspective of the time process. The agreement of the results with the previous behavioral experiments suggests that the structure and learning process of the proposed model are appropriate.     

The ATR-Chk1 pathway plays a role in the generation of centrosome aberrations induced by Rad51C dysfunction

Rad51C is a central component of two complexes formed by five Rad51 paralogs in vertebrates. These complexes are involved in repairing DNA double-strand breaks through homologous recombination. Despite accumulating evidence suggesting that the paralogs may prevent aneuploidy by controlling centrosome integrity, Rad51C's role in maintaining chromosome stability remains unclear. Here we demonstrate that Rad51C deficiency leads to both centrosome aberrations in an ATR-Chk1-dependent manner and increased aneuploidy in human cells. While it was reported that Rad51C deficiency did not cause centrosome aberrations in interphase in hamster cells, such aberrations were observed in interphase in HCT116 cells with Rad51C dysfunction. Caffeine treatment and down-regulation of ATR, but not that of ATM, reduced the frequency of centrosome aberrations in the mutant cells. Silencing of Rad51C by RNA interference in HT1080 cells resulted in similar aberrations. Treatment with a Chk1 inhibitor and silencing of Chk1 also reduced the frequency in HCT116 mutants. Accumulation of Chk1 at the centrosome and nuclear foci of γH2AX were increased in the mutants. Moreover, the mutant cells had a higher frequency of aneuploidy. These findings indicate that the ATR-Chk1 pathway plays a role in increased centrosome aberrations induced by Rad51C dysfunction.     

Mouse Shh is required for prechordal plate maintenance during brain and craniofacial morphogenesis

In humans, holoprosencephaly (HPE) is a common birth defect characterized by the absence of midline cells from brain, facial, and oral structures. To understand the pathoetiology of HPE, we investigated the involvement of mammalian prechordal plate (PrCP) cells in HPE pathogenesis and the requirement of the secreted protein sonic hedgehog (Shh) in PrCP development. We show using rat PrCP lesion experiments and DiI labeling that PrCP cells are essential for midline development of the forebrain, foregut endoderm, and ventral cranial mesoderm in mammals. We demonstrate that PrCP cells do not develop into ventral cranial mesoderm in Shh^−/− embryos. Using Shh^−/− and chimeric embryos we show that Shh signal is required for the maintenance of PrCP cells in a non-cell autonomous manner. In addition, the hedgehog (HH)-responding cells that normally appear during PrCP development to contribute to midline tissues, do not develop in the absence of Shh signaling. This suggests that Shh protein secreted from PrCP cells induces the differentiation of HH-responding cells into midline cells. In the present study, we show that the maintenance of a viable population of PrCP cells by Shh signal is an essential process in development of the midline of the brain and craniofacial structures. These findings provide new insight into the mechanism underlying HPE pathoetiology during dynamic brain and craniofacial morphogenesis.     

Altered Glucose Homeostasis in Mice with Liver-specific Deletion of Src Homology Phosphatase 2

The Src homology 2 domain-containing protein-tyrosine phosphatase Shp2 has been implicated in a variety of growth factor signaling pathways, but its role in insulin signaling has remained unresolved. In vitro studies suggest that Shp2 is both a negative and positive regulator of insulin signaling, although its physiological function in a number of peripheral insulin-responsive tissues remains unknown. To address the metabolic role of Shp2 in the liver, we generated mice with either chronic or acute hepatic Shp2 deletion using tissue-specific Cre-LoxP and adenoviral Cre approaches, respectively. We then analyzed insulin sensitivity, glucose tolerance, and insulin signaling in liver-specific Shp2-deficient and control mice. Mice with chronic Shp2 deletion exhibited improved insulin sensitivity and increased glucose tolerance compared with controls. Acute Shp2 deletion yielded comparable results, indicating that the observed metabolic effects are directly caused by the lack of Shp2 in the liver. These findings correlated with, and were most likely caused by, direct dephosphorylation of insulin receptor substrate (IRS)1/2 in the liver, accompanied by increased PI3K/Akt signaling. In contrast, insulin-induced ERK activation was dramatically attenuated, yet there was no effect on the putative ERK site on IRS1 (Ser⁶¹²) or on S6 kinase 1 activity. These studies show that Shp2 is a negative regulator of hepatic insulin action, and its deletion enhances the activation of PI3K/Akt pathway downstream of the insulin receptor.