α‐ketoglutarate delays age‐related fertility decline in mammals

The fecundity reduction with aging is referred as the reproductive aging which comes earlier than that of chronological aging. Since humans have postponed their childbearing age, to prolong the reproductive age becomes urgent agenda for reproductive biologists. In the current study, we examined the potential associations of α‐ketoglutarate (α‐KG) and reproductive aging in mammals including mice, swine, and humans. There is a clear tendency of reduced α‐KG level with aging in the follicle fluids of human. To explore the mechanisms, mice were selected as the convenient animal model. It is observed that a long term of α‐KG administration preserves the ovarian function, the quality and quantity of oocytes as well as the telomere maintaining system in mice. α‐KG suppresses ATP synthase and alterations of the energy metabolism trigger the nutritional sensors to down‐regulate mTOR pathway. These events not only benefit the general aging process but also maintain ovarian function and delay the reproductive decline. Considering the safety of the α‐KG as a naturally occurring molecule in energy metabolism, its utility in reproduction of large mammals including humans deserves further investigation.     

Weitere Untersuchungen an Nachkommen von Kürbis-Artbastarden

Zusammenfassung Aus 1950 durchgeführten Artkreuzungen zwischenCucurbita maxima Duch. und weichschaligemC. pepo L. wurden mittels Embryonenkultur F₁-Bastarde gewonnen. An Hand zweimaliger Rückkreuzung mitC. maxima und anschließender Selbstung gelang es, zum Teil wiederum mit Hilfe der Embryonenkultur, 4 verschiedene Bastardkombinationen bis in die F₄ zu verfolgen. In dieser Generation spalteten (1954 und 1955) bei Auswertung von 72 Familien mit insgesamt 733, davon 600 fertilen Pflanzen in 2 Bastardlinien resp. 3 Familien, insgesamt 4 weichschalige Pflanzen heraus. Da diese Pflanzen frei abblühten und das gewonnene Saatgut heterozygot war, mußten erneut zwei Selbstungsgenerationen aufgezogen werden, die in den Jahren 1956–58 mehrere erbreine Stämme weichschaliger Pflanzen lieferten.Nach Kurzer Einführung in die Anatomie der Samenschale und ihre verschiedenen Typen sowie in die bisherigen Ergebnisse genetischer Untersuchungen zur Frage der Testaausbildung wird an Hand der Spaltungsergebnisse beim erstmaligen Auftreten weichschaliger Pflanzen in der F₄ sowie der nach erneuter Selbstung in der F₆ erzielten Spaltungsverhältnisse aufgezeigt, daß das Merkmal weichschalig durchzwei Gene bedingt ist. Nach kurzer Besprechung von Spaltungen pachyspermer und leptospermer Pflanzen in der F₃ wird die Variabilität der Testaausbildung bis zum Auftreten weichschaliger Pflanzen beschrieben.In einem weiteren Kapitel wird die Variabilität in der Ausbildung der weichschaligen Testa der Bastardnachkommen, das Ergebnis der Selektion auf rein weichschalige Typen im Verlauf der 7. bis 11. Generation (1957–1964) und die Größenvariabilität der Samen der weichschaligen Typen im Vergleich zu den Ausgangsarten sowie einem Weltsortiment vonC. maxima erörtert. Zur Veranschaulichung dieser Verhältnisse wird die erstmalig vonF. Galton benutzte Methode der Contourellipsen herangezogen, deren Berechnung und zeichnerische Darstellung mit Hilfe der Großrechenanlage IBM 7090 erfolgte.Abschließend wurden die beobachtetenMendel-Spaltungen unter dem Gesichtspunkt der die Pollenmeiose sowie die Pollenentwicklung der F₁ charakterisierenden Störungen, ferner die Bedeutung des erzielten Ergebnisses für die Züchtung diskutiert. Es wird eine Formel für die Berechnung der Wahrscheinlichkeit mitgeteilt, mit der unter ähnlichen Bedingungen rezessive Pflanzen erwartet werden können, wenn das rezessive Merkmal durch n Faktoren bedingt ist und im Anschluß an die Artkreuzungj Rückkreuzungen mit der dominanten Art erforderlich sind. Auch auf die Bedeutung von Untersuchungen der vorliegenden Art für Fragen der Genlokalisation und Genanalyse wird hingewiesen.

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Further investigations on progeny of pumpkin species hybridsI. Seed formation, especially in progeny with soft seed coat, and the regularity in transmission of a recessive trait from one parental species to fertile progeny with characteristics of the other parental species

Summary Using embryo culture, we obtainedF ₁-hybrids from interspecific crosses realized in 1950 betweenCucurbita maxima Duch. and a form ofC. pepo L. with soft shell seed or weichschaligen Samen (a so called naked seed type). These and their descendants, the latter in part also obtained by embryo culture, were back-crossed toC. maxima, and theF ₃ selfed. In this way we obtained descendants from 4 different crosses between the two species.Studying (in 1954 and 1955) 72F ₄-families with a total of 733 (600 fertile) plants, we found 4 plants with soft shell seeds. They were descended from 3F ₄-families or from 2 crosses respectively between the above named species.Since these plants flowered in the presence of other progeny from our species crosses, their seed was heterozygous, and two generations of selfing were necessary to obtain (in 1956–1958) different true breeding families, whose plants furnished homozygous soft shell seed.The anatomy of seed coats and results of studies by other authors on the genetic control of different seed coat types are discussed briefly. Given the segregation ratios in theF ₄ of our soft shell seeds, as well as those obtained inF ₆ after renewed selfing, it is shown that the trait soft shell is controlled by two genes. After a short discussion of segregation in theF ₃ of pachyspermic and leptospermic plants, the variability of seed coat formation until the appearance of soft shell seed is described.In a special chapter we discuss the variability of the soft-shell seed character in hybrid progeny, the result of our selection experiments from the 7^th up to the 12^th generation (1957–1964), and the variability in the seed size of our types compared with that of pure species and of a collection ofC. maxima. To illustrate these relationships we used the method of contour-ellipses introduced byF. Galton. These ellipses were computed and designed by means of the computer IBM 7090.Finally we discuss Mendelian segregation of our plants in the light of abnormalities characteristic for meiosis of pollen-mother-cells and pollen development inF ₁, and the significance of the results to plant breeding. A formula is given for calculating the probability of obtaining recessive plants when the recessive trait depends onn factors, and whenj backcrosses to the dominant variety are necessary to establish a stable strain. The importance of experiments of this kind to the problem of gene localization and gene analysis is also pointed out.

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Herrn Professor Dr. Dr. Dr. h. c. O.Heinisch, geb. 23. 4. 1896, gest. 3. 5. 1966, zum Gedächtnis.     

Genomic insights into selection for heterozygous alleles and woody traits in Populus tomentosa

Heterozygous alleles are widespread in outcrossing and clonally propagated woody plants. The variation in heterozygosity that underlies population adaptive evolution and phenotypic variation, however, remains largely unknown. Here, we describe a de novo chromosome-level genome assembly of Populus tomentosa, an economic and ecologically important native tree in northern China. By resequencing 302 natural accessions, we determined that the South subpopulation (Pop_S) encompasses the ancestral strains of P. tomentosa, while the Northwest subpopulation (Pop_NW) and Northeast subpopulation (Pop_NE) experienced different selection pressures during population evolution, resulting in significant population differentiation and a decrease in the extent of heterozygosity. Analysis of heterozygous selective sweep regions (HSSR) suggested that selection for lower heterozygosity contributed to the local adaptation of P. tomentosa by dwindling gene expression and genetic load in the Pop_NW and Pop_NE subpopulations. Genome-wide association studies (GWAS) revealed that 88 single nucleotide polymorphisms (SNPs) within 63 genes are associated with nine wood composition traits. Among them, the selection for the homozygous AA allele in PtoARF8 is associated with reductions in cellulose and hemicellulose contents by attenuating PtoARF8 expression, and the increase in lignin content is attributable to the selection for decreases in exon heterozygosity in PtoLOX3 during adaptive evolution of natural populations. This study provides novel insights into allelic variations in heterozygosity associated with adaptive evolution of P. tomentosa in response to the local environment and identifies a series of key genes for wood component traits, thereby facilitating genomic-based breeding of important traits in perennial woody plants.     

Cardiac telocytes exist in the adult Xenopus tropicalis heart

Recent research has revealed that cardiac telocytes (CTs) play an important role in cardiac physiopathology and the regeneration of injured myocardium. Recently, we reported that the adult Xenopus tropicalis heart can regenerate perfectly in a nearly scar‐free manner after injury via apical resection. However, whether telocytes exist in the X tropicalis heart and are affected in the regeneration of injured X tropicalis myocardium is still unknown. The present ultrastructural and immunofluorescent double staining results clearly showed that CTs exist in the X tropicalis myocardium. CTs in the X tropicalis myocardium were mainly twined around the surface of cardiomyocyte trabeculae and linked via nanocontacts between the ends of the telopodes, forming a three‐dimensional network. CTs might play a role in the regeneration of injured myocardium.     

Gilteritinib induces PUMA‐dependent apoptotic cell death via AKT/GSK‐3β/NF‐κB pathway in colorectal cancer cells

As a highly potent and highly selective oral inhibitor of FLT3/AXL, gilteritinib showed activity against FLT3D835 and FLT3‐ITD mutations in pre‐clinical testing, although its role on colorectal cancer (CRC) cells is not yet fully elucidated. We examined the activity of gilteritinib in suppressing growth of CRC and its enhancing effect on other drugs used in chemotherapy. In this study, we observed that, regardless of p53 status, treatment using gilteritinib induces PUMA in CRC cells via the NF‐κB pathway after inhibition of AKT and activation of glycogen synthase kinase 3β (GSK‐3β). PUMA was observed to be vital for apoptosis in CRC cells through treatment of gilteritinib. Moreover, enhancing induction of PUMA through different pathways could mediate chemosensitization by using gilteritinib. Furthermore, PUMA deficiency revoked the antitumour role of gilteritinib in vivo. Thus, our results indicate that PUMA mediates the antitumour activity of gilteritinib in CRC cells. These observations are critical for the therapeutic role of gilteritinib in CRC.     

Seasonal variation and correlation analysis of vitamin D and parathyroid hormone in Hangzhou,Southeast China

This study aimed to describe the 25‐hydroxyvitamin D (25(OH)D) and parathyroid hormone (PTH) status of Southeast Chinese individuals influenced by season. The secondary aim was to determine the cutoff for sufficient 25(OH)D in a four‐season region. From January 2011 to June 2014, a total of 17 646 individuals were evaluated in our study. The serum levels of PTH were detected simultaneously in 5579 cases. A total of 25(OH)D and intact PTH were measured by the electrochemiluminescent immunoassay. The distribution of the concentration, prevalence and seasonal variability of 25(OH)D and PTH were studied. The mean 25(OH)D concentration in our study was 43.00(30.40) nmol/L. The prevalence of insufficiency (25(OH)D < 50 nmol/L) was 62.87% and that of deficiency (<30 nmol/L) was 28.54%. Mean serum 25(OH)D levels revealed a limited sinusoidal profile throughout the year and were significantly higher in Autumn. On the other hand, PTH levels showed an opposite response to seasonal effects relative to 25(OH)D. Age, BMI and daylight were not significantly correlated with 25(OH)D and serum PTH reached a plateau at higher values of serum 25(OH)D of 42.86 nmol/L. This study demonstrated that Vitamin D insufficiency is highly prevalent in Southeast China. The concentration of 25(OH)D in the male group was generally higher than that in the female group. Seasonal variation was an important aspect of 25(OH)D and PTH concentration. This study revealed that the optimal serum threshold of 25(OH)D for bone health should be between 40 and 50 nmol/L for Southeast Chinese individuals.     

Exogenous neuritin treatment improves survivability and functions of Schwann cells with improved outgrowth of neurons in rat diabetic neuropathy

Pathogenesis and treatment for diabetic neuropathy are still complex. A deficit of neurotrophic factors affecting Schwann cells is a very important cause of diabetic neuropathy. Neuritin is a newly discovered potential neurotrophic factor. In this study, we explored the effect of exogenous neuritin on survivability and functions of diabetic Schwann cells of rats with experimental diabetic neuropathy. Diabetic neuropathy was induced in rats. 12‐week diabetic rats contrasted with non‐diabetic normal rats had decreased levels of serum neuritin and slowed nerve conduction velocities (NCVs). Schwann cells isolated from these diabetic rats and cultured in high glucose showed reduced cell neuritin mRNA and protein and supernatant neuritin protein, increased apoptosis rates, increased caspase‐3 activities and progressively reduced viability. In contrast, exogenous neuritin treatment reduced apoptosis and improved viability, with elevated Bcl‐2 levels (not Bax) and decreased caspase‐3 activities. Co‐cultured with diabetic Schwann cells pre‐treated with exogenous neuritin in high glucose media, and diabetic DRG neurons showed lessened decreased neurite outgrowth and supernatant NGF concentration occurring in co‐culture of diabetic cells. Exogenous neuritin treatment ameliorated survivability and functions of diabetic Schwann cells of rats with diabetic neuropathy. Our study may provide a new mechanism and potential treatment for diabetic neuropathy.