The effect of nutrient deprivation on proteasome activity in 4-week-old mice and 24-week-old mice.

Recently, we have begun to better understand the regulatory mechanisms of proteasome activity in response to the nutritional state. In this study, we analyzed the expression and function of proteasomes in the livers and brains where changes in the metabolic system occur in vivo during short-term starvation. In the livers of 4-week-old mice, proteasome activity decreased with fasting time, whereas brain proteasome activity remained unchanged by up to 24 h of fasting and then decreased. However, liver and brain proteasome activity in 24-week-old mice decreased by fasting for 24 h and then recovered. There was no significant change in the expression levels of the subunits that make up the proteasomes in livers and brains regardless of age, and there was no change in the molecular size of the formed proteasome. Interestingly, Ump1, a proteasome assembly protein, accumulated with changes in proteasome activity. When the fasted state returned to a fed state, the proteasome activity in the brain was restored to almost the same level as in the fed state, but the proteasome activity in the liver was not restored to that of the fed state. In this state, the assembly protein Ump1 continued to accumulate. These findings suggest that (1) the expression of Ump1 is controlled by the nutritional state, and (2) the proteasome formation mechanism may differ depending on the organ.

A cat with myelodysplastic syndrome by administration of the methylation inhibitor Azacytidine.

A 5-year-old female cat with nonregenerative anemia and thrombocytopenia was diagnosed with myelodysplastic syndromes (MDS), since peripheral blood and bone marrow (BM) examination revealed various dysplasias and a blast ratio of 19%. Chemotherapy with azacytidine (AZA; 70-35 mg/m2, 3-5 days, three cycles) and treatment with prednisolone, antibiotics, and vitamin K2, and blood transfusion were performed. On day 106, blast cells and dysplasia had decreased in the BM, and the cat remained alive for at least 1,474 days. This report is the first on feline MDS treated with AZA, suggesting appropriate drug dosage, interval and effective combination should be investigated and the pharmacological and cell biological mechanisms needs to be elucidated in the future.

Giving Back to Get Back: Assessment of Native and Non-Native American Perceptions of Generativity.

Previous research has shown the negative effects of loneliness on quality of life, all-cause mortality, and morbidity. Generativity is the concept of giving something back to younger generations and is theorized to improve a sense of meaning and fulfillment in elders' lives. This survey study examined the relationships between three constructs: generativity, loneliness, and quality of life in elders living in rural Northern California in a largely Native American community (N=98). While causation cannot be determined in this cross-sectional study, the findings suggest that improving the level of generativity in rural elders may enhance their quality of life. Creating venues in which elders can interact with younger generations may be beneficial in the future.

Complications arising from transfemoral, percutaneous implantation of an indwelling port-catheter system for hepatic infusion chemotherapy: Case series of the management and salvage of the system.

INTRODUCTION: Regional hepatic arterial infusion of chemotherapy is performed for unresectable liver tumors via percutaneously implanted port-catheter systems; while these port-catheter systems are effective administration routes, they are associated with various complications. Withdrawal of the system is considered if the complications occur, but repeated hepatic arterial infusion of chemotherapy (HAIC) via an implanted port-catheter system is a last-resort treatment for unresectable advanced liver cancer, and the treatment must be continued. We discuss various cases with complications arising in the indwelling port area in hepatic arterial infusion of chemotherapy and report whether the system was salvaged. METHODS: Between August 2013 and October 2017, eight patients (six males and two females) aged 61-80 years (mean age 76.6 years) with complications arising in a transfemoral indwelling port site for HAIC were referred to our department. All patients requested preservation of the system, especially the catheter. Each patient was assessed for the presence of "gross infection" based on a comprehensive evaluation of clinical findings and blood test results. In cases of "no gross infection," we performed catheter salvage procedures. If there was no clinical improvement following the catheter salvage procedure, the port-catheter system was withdrawn. This research work has been reported in line with the PROCESS criteria. RESULTS: The port-catheter systems were withdrawn in two patients: one due to lasting infection and the other due to ulcer recurrence. Three cases were treated by removal of hematoma through an incision and ointment. The system was withdrawn in one of these cases due to exacerbation of ulcer; thus, the catheters were salvaged in five patients. None of these five patients experienced a relapse from 3 months to over 1 year after the procedure. CONCLUSION: The success of subcutaneous HAIC significantly impacts a patient's prognosis, especially for unresectable tumors and residual tumor recurrences. Initially, we chose to preserve the devices without removal, particularly if there was no infection. However, this approach led to a delay in chemotherapy, prolongation of healing time, and additional complications. These cases demonstrate the importance of a thorough consultation with the patient's oncologist to discuss whether or not the device should be conserved.

Plastidial Folate Prevents Starch Biosynthesis Triggered by Sugar Influx into Non-Photosynthetic Plastids of Arabidopsis.

Regulation of sucrose-starch interconversion in plants is important to maintain energy supplies necessary for viability and growth. Arabidopsis mutants were screened for aberrant responses to sucrose to identify candidates with a defect in the regulation of starch biosynthesis. One such mutant, fpgs1-4, accumulated substantial amounts of starch in non-photosynthetic cells. Dark-grown mutant seedlings exhibited shortened hypocotyls and accumulated starch in etioplasts when supplied with exogenous sucrose/glucose. Similar starch accumulation from exogenous sucrose was observed in mutant chloroplasts, when photosynthesis was prevented by organ culture in darkness. Molecular genetic analyses revealed that the mutant was defective in plastidial folylpolyglutamate synthetase, one of the enzymes engaged in folate biosynthesis. Active folate derivatives are important biomolecules that function as cofactors for a variety of enzymes. Exogenously supplied 5-formyl-tetrahydrofolate abrogated the mutant phenotypes, indicating that the fpgs1-4 mutant produced insufficient folate derivative levels. In addition, the antifolate agents methotrexate and 5-fluorouracil induced starch accumulation from exogenously supplied sucrose in dark-grown seedlings of wild-type Arabidopsis. These results indicate that plastidial folate suppresses starch biosynthesis triggered by sugar influx into non-photosynthetic cells, demonstrating a hitherto unsuspected link between plastidial folate and starch metabolism.

Shoot-to-root mobile polypeptides involved in systemic regulation of nitrogen acquisition.

Plants uptake nitrogen (N) from the soil mainly in the form of nitrate. However, nitrate is often distributed heterogeneously in natural soil. Plants, therefore, have a systemic long-distance signalling mechanism by which N starvation on one side of the root leads to a compensatory N uptake on the other N-rich side1,2. This systemic N acquisition response is triggered by a root-to-shoot mobile peptide hormone, C-TERMINALLY ENCODED PEPTIDE (CEP), originating from the N-starved roots3,4, but the molecular nature of the descending shoot-to-root signal remains elusive. Here, we show that phloem-specific polypeptides that are induced in leaves upon perception of root-derived CEP act as descending long-distance mobile signals translocated to each root. These shoot-derived polypeptides, which we named CEP DOWNSTREAM 1 (CEPD1) and CEPD2, upregulate the expression of the nitrate transporter gene NRT2.1 in roots specifically when nitrate is present in the rhizosphere. Arabidopsis plants deficient in this pathway show impaired systemic N acquisition response accompanied with N-deficiency symptoms. These fundamental mechanistic insights should provide a conceptual framework for understanding systemic nutrient acquisition responses in plants.

A peptide hormone required for Casparian strip diffusion barrier formation in Arabidopsis roots.

Plants achieve mineral ion homeostasis by means of a hydrophobic barrier on endodermal cells called the Casparian strip, which restricts lateral diffusion of ions between the root vascular bundles and the soil. We identified a family of sulfated peptides required for contiguous Casparian strip formation in Arabidopsis roots. These peptide hormones, which we named Casparian strip integrity factor 1 (CIF1) and CIF2, are expressed in the root stele and specifically bind the endodermis-expressed leucine-rich repeat receptor kinase GASSHO1 (GSO1)/SCHENGEN3 and its homolog, GSO2. A mutant devoid of CIF peptides is defective in ion homeostasis in the xylem. CIF genes are environmentally responsive. Casparian strip regulation is not merely a passive process driven by root developmental cues; it also serves as an active strategy to cope with adverse soil conditions.

Family and partner interpersonal violence among American Indians/Alaska Natives.

Family and partner interpersonal violence are common among American Indian/Alaska Native (AI/AN) populations. AI/AN women have the second highest prevalence of violence against women among all racial/ethnic groups in the United States, and child abuse prevalence rates in AI/AN populations are among the highest. Elder abuse in AI/AN is also an important concern, although data on this are sparse. This review describes the epidemiology of child abuse, violence against women, and elder abuse among AI/AN, including prevalence and associated risk factors. The authors discuss potential reasons for the high burden of interpersonal violence among AI/AN, including common risk factors. Important limitations in existing literature are also highlighted, along with recommendations for future research on this topic.

Auxin-cytokinin interactions in the control of shoot branching.

In many plant species, the intact main shoot apex grows predominantly and axillary bud outgrowth is inhibited. This phenomenon is called apical dominance, and has been analyzed for over 70 years. Decapitation of the shoot apex releases the axillary buds from their dormancy and they begin to grow out. Auxin derived from an intact shoot apex suppresses axillary bud outgrowth, whereas cytokinin induced by decapitation of the shoot apex stimulates axillary bud outgrowth. Here we describe the molecular mechanisms of the interactions between auxin and cytokinin in the control of shoot branching.

Auxin controls local cytokinin biosynthesis in the nodal stem in apical dominance.

In intact plants, the shoot apex grows predominantly and inhibits outgrowth of axillary buds. After decapitation of the shoot apex, outgrowth of axillary buds begins. This phenomenon is called an apical dominance. Although the involvement of auxin, which represses outgrowth of axillary buds, and cytokinin (CK), which promotes outgrowth of axillary buds, has been proposed, little is known about the underlying molecular mechanisms. In the present study, we demonstrated that auxin negatively regulates local CK biosynthesis in the nodal stem by controlling the expression level of the pea (Pisum sativum L.) gene adenosine phosphate-isopentenyltransferase (PsIPT), which encodes a key enzyme in CK biosynthesis. Before decapitation, PsIPT1 and PsIPT2 transcripts were undetectable; after decapitation, they were markedly induced in the nodal stem along with accumulation of CK. Expression of PsIPT was repressed by the application of indole-3-acetic acid (IAA). In excised nodal stem, PsIPT expression and CK levels also increased under IAA-free conditions. Furthermore, beta-glucuronidase expression, under the control of the PsIPT2 promoter region in transgenic Arabidopsis, was repressed by an IAA. Our results indicate that in apical dominance one role of auxin is to repress local biosynthesis of CK in the nodal stem and that, after decapitation, CKs, which are thought to be derived from the roots, are locally biosynthesized in the nodal stem rather than in the roots.