Apoptosis is a cellular suicide program that plays a critical role in development and human diseases, including cancer. Cancer cells evade apoptosis, thereby enabling excessive proliferation, ...survival under hypoxic conditions, and acquired resistance to therapeutic agents. Among various mechanisms that contribute to the evasion of apoptosis in cancer, metabolism is emerging as one of the key factors. Cellular metabolites can regulate functions of pro- and antiapoptotic proteins. In turn, p53, a regulator of apoptosis, also controls metabolism by limiting glycolysis and facilitating mitochondrial respiration. Consequently, with dysregulated metabolism and p53 inactivation, cancer cells are well-equipped to disable the apoptotic machinery. In this article, we review how cellular apoptosis is regulated and how metabolism can influence the signaling pathways leading to apoptosis, especially focusing on how glucose and lipid metabolism are altered in cancer cells and how these alterations can impact the apoptotic pathways.
The coexistence and competition between superconductivity and electronic orders, such as spin or charge density waves, have been a central issue in high transition-temperature (Tc) superconductors. ...Unlike other iron-based superconductors, FeSe exhibits nematic ordering without magnetism whose relationship with its superconductivity remains unclear. Moreover, a pressure-induced fourfold increase of Tc has been reported, which poses a profound mystery. Here we report high-pressure magnetotransport measurements in FeSe up to ∼15 GPa, which uncover the dome shape of magnetic phase superseding the nematic order. Above ∼6 GPa the sudden enhancement of superconductivity (Tc≤38.3 K) accompanies a suppression of magnetic order, demonstrating their competing nature with very similar energy scales. Above the magnetic dome, we find anomalous transport properties suggesting a possible pseudogap formation, whereas linear-in-temperature resistivity is observed in the normal states of the high-Tc phase above 6 GPa. The obtained phase diagram highlights unique features of FeSe among iron-based superconductors, but bears some resemblance to that of high-Tc cuprates.
Abstract
The interplay among magnetism, electronic nematicity, and superconductivity is the key issue in strongly correlated materials including iron-based, cuprate, and heavy-fermion ...superconductors. Magnetic fluctuations have been widely discussed as a pairing mechanism of unconventional superconductivity, but recent theory predicts that quantum fluctuations of nematic order may also promote high-temperature superconductivity. This has been studied in FeSe
1−
x
S
x
superconductors exhibiting nonmagnetic nematic and pressure-induced antiferromagnetic orders, but its abrupt suppression of superconductivity at the nematic end point leaves the nematic-fluctuation driven superconductivity unconfirmed. Here we report on systematic studies of high-pressure phase diagrams up to 8 GPa in high-quality single crystals of FeSe
1−
x
Te
x
. When Te composition
x
(Te) becomes larger than 0.1, the high-pressure magnetic order disappears, whereas the pressure-induced superconducting dome near the nematic end point is continuously found up to
x
(Te) ≈ 0.5. In contrast to FeSe
1−
x
S
x
, enhanced superconductivity in FeSe
1−
x
Te
x
does not correlate with magnetism but with the suppression of nematicity, highlighting the paramount role of nonmagnetic nematic fluctuations for high-temperature superconductivity in this system.
Abstract
A fundamental issue concerning iron-based superconductivity is the roles of electronic nematicity and magnetism in realising high transition temperature (
T
c
). To address this issue, FeSe ...is a key material, as it exhibits a unique pressure phase diagram involving non-magnetic nematic and pressure-induced antiferromagnetic ordered phases. However, as these two phases in FeSe have considerable overlap, how each order affects superconductivity remains perplexing. Here we construct the three-dimensional electronic phase diagram, temperature (
T
) against pressure (
P
) and isovalent S-substitution (
x
), for FeSe
1−
x
S
x
. By simultaneously tuning chemical and physical pressures, against which the chalcogen height shows a contrasting variation, we achieve a complete separation of nematic and antiferromagnetic phases. In between, an extended non-magnetic tetragonal phase emerges, where
T
c
shows a striking enhancement. The completed phase diagram uncovers that high-
T
c
superconductivity lies near both ends of the dome-shaped antiferromagnetic phase, whereas
T
c
remains low near the nematic critical point.
Many eusocial insects can distinguish nestmates from non-nestmate conspecifics, which ensures that altruistic behavior is directed toward close relatives. In termites, however, colonies exhibit ...various responses to non-nestmates: from killing to accepting as a colony member. Why and how termite colonies adopt closed versus open societies remain largely unknown, while it is presumably related to not only genetic but also social-environmental factors. Here, we show that kings and queens play a key role in maintaining high aggression levels of workers and soldiers toward non-nestmate intruders in the subterranean termite
Reticulitermes speratus
. The level of aggression toward non-nestmate conspecifics was significantly lower in “royal-absent” colonies compared to “royal-present” colonies. In addition, the proportion of workers and soldiers exhibiting aggressive behaviors toward non-nestmates decreased in the absence of kings and queens. Our results demonstrate that social conditions, including royal presence, can influence intercolonial interactions, and may explain why previous studies of termite aggression have reported contradictory findings. This study provides important new insights into nestmate recognition and colony defense in eusocial insects.
The symbiosis between lower termites and their intestinal microorganisms, essential for wood digestion, is well characterized. Termites exhibit a reproductive division of labor—kings and queens ...specialize in reproduction, and workers are responsible for foraging and feeding the colony members. Therefore, the gut microbial community in royals is expected to be down-regulated because it is less important than that in workers. Indeed, we recently reported that, in the termite species
Reticulitermes speratus
, workers have symbiotic protists; kings, and neotenic queens in mature field colonies completely lose protists in their guts. However, the dynamics of the protist community during caste differentiation remain unclear. In this study, we investigated the relationship between the abundance of intestinal protists and the neotenic differentiation of
R. speratus
. First, we confirmed that both sexes of late instar nymphs possessed intestinal protist communities like those of workers. Nevertheless, after molting for neotenic differentiation, they lost most of their intestinal protists and did not regain them. Based on our behavioral observation, workers, nymphs, and neotenics received proctodeal food from surrounding workers. This suggests protists can enter neotenics’ guts, while they cannot establish after the neotenic differentiation. Our study highlights that the interaction between termites and gut microbes changes dynamically during caste differentiation.
The aim of this review is to evaluate the long-term effectiveness of calcium silicate-based cement (CS) and calcium hydroxide (CH) for direct pulp capping (DPC) to human pulp-exposed permanent teeth. ...An electronic search and manual search were performed on 21 June 2019. Long-term clinical and radiographic evaluations of the effectiveness of CS and CH for DPC to human pulp-exposed teeth were included, and data extraction, risk-of-bias assessment and meta-analyses were performed. From 645 identified articles, 7 articles met the eligibility criteria. The meta-analyses comparing CS with CH and Biodentine with mineral trioxide aggregates (MTA) on DPC success rate were performed, and significant difference was observed between CS and CH (risk ratio=1.20; p=0.005), whereas no significant difference was observed between Biodentine and MTA. CS seems to be a more effective and predictable DPC material than CH; however, these analyses are based on the studies judged at high risk of bias.
Evasion of apoptosis allows many cancers to resist chemotherapy. Apoptosis is mediated by the serial activation of caspase family proteins. These proteases are often activated upon the release of ...cytochrome c from the mitochondria, which is promoted by the proapoptotic Bcl-2 family protein, Bax. This function of Bax is enhanced by the MOAP-1 (modulator of apoptosis protein 1) protein in response to DNA damage. Previously, we reported that MOAP-1 is targeted for ubiquitylation and degradation by the APC/C
ubiquitin ligase. In this study, we identify the HECT (homologous to the E6-AP carboxyl terminus) family E3 ubiquitin ligase, UBR5, as a novel ubiquitin ligase for MOAP-1. We demonstrate that UBR5 interacts physically with MOAP-1, ubiquitylates MOAP-1 in vitro and inhibits MOAP-1 stability in cultured cells. In addition, we show that Dyrk2 kinase, a reported UBR5 interactor, cooperates with UBR5 in mediating MOAP-1 ubiquitylation. Importantly, we found that cisplatin-resistant ovarian cancer cell lines exhibit lower levels of MOAP-1 accumulation than their sensitive counterparts upon cisplatin treatment, consistent with the previously reported role of MOAP-1 in modulating cisplatin-induced apoptosis. Accordingly, UBR5 knockdown increased MOAP-1 expression, enhanced Bax activation and sensitized otherwise resistant cells to cisplatin-induced apoptosis. Furthermore, UBR5 expression was higher in ovarian cancers from cisplatin-resistant patients than from cisplatin-responsive patients. These results show that UBR5 downregulates proapoptotic MOAP-1 and suggest that UBR5 can confer cisplatin resistance in ovarian cancer. Thus UBR5 may be an attractive therapeutic target for ovarian cancer treatment.
Termite royals (queen and king) exhibit extraordinary longevity without sacrificing reproductive performance, unlike most animals, in whom lifespan is generally negatively associated with ...reproduction. Therefore, the regulatory mechanisms underlying longevity have attracted much attention. Although the ageing process is influenced by environmental factors in many insects during their life cycle, it remains unclear whether any factors have an effect on the extended survival and high reproductive capacity of termite royals. Here, we show that hypoxia, possibly an important environmental factor in the nests, enhances survival and reproductive activity in incipient royals of the subterranean termite Reticulitermes speratus compared with those in control conditions. Quantitative real‐time PCR analysis revealed that the expression levels of the vitellogenin gene in queens are maintained to a greater extent under hypoxic conditions than under control conditions. The expression levels of the antioxidant enzyme genes RsCAT1 and RsPHGPX are also significantly promoted by hypoxia in queens and kings respectively. These results suggest that hypoxic exposure can contribute in part to achieving high reproductive output by altering gene expression after founding of colonies in the royals. Our study provides novel insights into the effect of a nest environment on the reproductive characteristics in termite royals.
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