Glucocorticoid induced osteoporosis and mechanisms of intervention

Indiana University-Purdue University Indianapolis (IUPUI)Glucocorticoid excess is a leading cause of osteoporosis. The loss of bone mass and strength corresponds to the increase in fractures exhibited after three months of glucocorticoid therapy. Glucocorticoids induce the bone cellular responses of deceased bone formation, increased osteoblast/osteocyte apoptosis, and transient increased bone resorption, which result in rapid bone loss and degradation of bone microarchitecture. The current standard of care for osteoporosis is bisphosphonate treatment; however, these agents further suppress bone formation and increase osteonecrosis and low energy atypical fracture risks. Thus, there is an unmet need for interventions that protect from glucocorticoid therapy. The purpose of these studies was to investigate novel mechanisms that potentially interfere with glucocorticoid-induced bone loss. We chose to explore pathways that regulate endoplasmic reticulum stress, the canonical Wnt pathway, and Pyk2 activity. Pharmacologic reduction of endoplasmic reticulum stress through salubrinal administration protected against glucocorticoid-induced bone loss by preservation of bone formation and osteoblast/osteocyte viability. In contrast, inhibition of Wnt antagonist Sost/sclerostin and inhibition of Pyk2 signaling did not prevent glucocorticoid-induced reductions in bone formation; however, both Sost/sclerostin and Pyk2 deficiency protected against bone loss through inhibition of increases in resorption. Overall, these studies demonstrate the significant contributions of reductions in bone formation, increased osteoblast/osteocyte apoptosis, and elevations in resorption to the rapid 6-12% bone loss exhibited during the first year of glucocorticoid therapy. However, glucocorticoid excess also induces skeletal muscle weakness, which is not reversed by bisphosphonate treatment or the interventions reported here of salubrinal, Sost/sclerostin inhibition, or Pyk2 deficiency. Further, the novel finding of increased E3 ubiquitin ligase atrophy signaling induce by glucocorticoids in both bone and muscle, by tissue-specific upstream mechanisms, provides opportunities for therapeutic combination strategies. Thus, future studies are warranted to investigate the role of E3 ubiquitin ligase signaling in the deleterious glucocorticoid effects of bone and muscle

Effect of Donepezil on Group II mGlu Receptor Agonist- or Antagonist-Induced Amnesia on Passive Avoidance in Mice

We examined the effect of the acetylcholinesterase (ACHE) inhibitor, donepezil hydrocloride (DONP), on group II metabotropic glutamate (mGlu) receptor agonist- or antagonist-induced amnesia in the step-through passive avoidance task in male mice. DCG-IV, a group II mGlu receptor agonist, at dose of 50 ng and LY341495, a group II mGlu receptor antagonist, at dose of 300 ng, significantly attenuated the latency on the step-through task. The subcutaneous injection of DONP at dose of 1 mg/kg 1 hour before passive avoidance performance ameliorated the amnesia induced by DCG-IV and LY341495, whereas donepezil alone did not affect task latency. The results suggest that activation of group II mGlu receptors and disinhibition of the cAMP/PKA signaling pathway (caused by group II mGlu receptor antagonist) have a negative action on step-through passive avoidance memory performance, and that group II mGlu receptors and ACh interact to modulate learning and memory function

RN7SL1 may be translated under oncogenic conditions

Hara T., Meng S., Tsuji Y., et al. RN7SL1 may be translated under oncogenic conditions. Proceedings of the National Academy of Sciences of the United States of America 121, (2024); https://doi.org/10.1073/pnas.2312322121.RN7SL1 (RNA component of signal recognition particle 7SL1), a component of the signal recognition particle, is a non-coding RNA possessing a small ORF (smORF). However, whether it is translated into peptides is unknown. Here, we generated the RN7SL1-Green Fluorescent Protein (GFP) gene, in which the smORF of RN7SL1 was replaced by GFP, introduced it into 293T cells, and observed cells emitting GFP fluorescence. Furthermore, RNA-seq of GFP-positive cells revealed that they were in an oncogenic state, suggesting that RN7SL1 smORF may be translated under special conditions

ワーク・ライフ・バランスと乳幼児を持つ夫婦の育児の協同 : 日本の中の多様性

本研究はワーク・ライフ・バランスと乳幼児を持つ夫婦の育児の協同について検討することを目的とした。諸外国と比べて日本の母親は「育児不安」が高いことが特徴的である。また、日本では少子化が進行し、合計特殊出生率は1.3前後を推移している。しかしながら日本国内にも地域による違いがみられる。出生率や働く女性の割合が比較的高い地域があり、福井県はそのひとつである。一方、東京は出生率が大きく低下し、働く女性の割合も低い地域のひとつである。この論文では、福井県と東京の乳幼児を持つ家族の育児の協同を親の属性や生活時間、「育児行動」「育児感情」などの観点から比較した。This study examines work-life balance and co-parenting in families with preschool children. In Japan, child-rearing anxiety is a serious concern, especially when a mother cannot expect sufficient support from her spouse. The decline of birth rate is a critical issue in Japan, but there exist variations in this phenomenon. Fukui Prefecture has one of the highest birth rates and number of working women, while Tokyo has one of the lowest values in both. This study compares co-parenting in families with small children in Fukui Prefecture and Tokyo from various perspectives such as the demographic backgrounds of couples, their perception of child rearing, and co-parenting

父親と母親の職業生活及び家族生活と家事・育児行動

本研究はワーク・ライフ・バランスと乳幼児を持つ夫婦の育児の協同について検討することを目的とした。この論文では、調査対象となった366組の夫婦を、母親の就業形態により3群化し、乳幼児を持つ家族の育児の協同を、「育児行動」「育児感情」などの観点から比較した。その結果、パートタイムの仕事を持つ母親は夫の育児参加がフルタイムの仕事を持つ母親と比較して有意に低く、専業主婦の母親と比較して有意差はない。また、パートタイムの仕事を持つ母親は子育てへの肯定感が他の2群と比較して有意に低く、それはパートタイムの仕事を持つ父親においても同様であった。This study aims to examine the work-life balance and co-parenting in families with preschool children. Participants were 366 couples whose children were in preschool. Co-parenting and child-rearing anxiety were compared among three groups: couples in which the wives have full-time jobs, couples in which the wives have part-time jobs, and those in which the wives are housewives. Results indicated that mothers who have part-time jobs receive the least support from their husbands in both co-parenting and housekeeping. In addition, the mothers\u27 positive feelings toward childreaing were lower in this group than the other two groups

育児期家族の生活と心理

本研究は、 育児期家族において、 社会・人口動態的な変数が、 父親と母親の自己認識や性別役割分業意識、 夫婦間コミュニケーション、 心理的ストレスにどのような影響を与え、 それが育児の協同にどうかかわっているかを検討した。 対象者は乳幼児を育てる366組の夫婦である。 主な結果は、 (1) 父親の労働時間が長い場合、 子どもの身体的な世話の頻度が少ない。 (2) 夫婦間コミュニケーションがよいと、 父親は子どものしつけ、 遊びの行動を多くする。 (3) 父母の自尊心は育児への肯定感と相関があるが、 母親の就業形態による自尊心に顕著な違いはみられない。 (4) 心理的ストレスは有職母親の方が父親より高いが、 仕事から家庭へのネガティブ・スピルオーバーは父親の方が高く、 家庭内のミクロのジェンダー・ポリティックスの可能性が示唆された。The purpose of this study is to examine work-life balance and co-parenting in families of preschoolers. The Participants were 366 couples. The results indicated that the father’s long working hours reduce the frequency to take care of their children. Stress in working mothers was higher than that in fathers, and yet, the negative spill over from work to home was higher among fathers than working mothers. This may be due to micro gender-politics within family

Drastic shift in flowering phenology of F₁ hybrids causing rapid reproductive isolation in Imperata cylindrica in Japan

1. Hybridization is a major source of phenotypic variation and a driving force for evolution. Although novel hybrid traits can often disrupt adaptive relationships between the parental phenotypes and their environments, how new hybrid traits disrupt local adaptation remains unclear. Here, we report how a new phenotype of hybrids between two Imperata cylindrica ecotypes contributes to rapid reproductive isolation from their parents and affects hybrid fitness. 2. We analysed 350 accessions of I. cylindrica collected from the 1980s to the 2010s throughout Japan to explore the genetic population structure of the hybrids. We surveyed the flowering periods, seed set, and germination of two ecotypes and their hybrids in both natural habitats and common gardens. 3. Genetic analyses of population structure revealed that the hybrid populations consisted of only F1 individuals, without advanced generation hybrids. The flowering phenology of the F1 plants was delayed until autumn, 5–6 months later than the parental ecotypes. The drastic shift in flowering phenology prevents F1s from backcrossing. In addition, it changes their seed dispersal time to winter. Germination is inhibited by low temperatures, and the seeds likely decay before the next spring, resulting in the absence of an F2 generation. We identified the environmental mismatch of the F1 population as a specific mechanism for the maintenance of an only F1 population. 4. Synthesis. We have demonstrated that this flowering phenology mismatch promotes reproductive isolation between the parents and F1s and affects various temporal components of the hybrids, resulting in a unique hybrid population consisting only of F1s. This system sheds light on the importance of hybrid traits in driving rapid reproductive isolation