SIRT6 Is Responsible for More Efficient DNA Double-Strand Break Repair in Long-Lived Species.

DNA repair has been hypothesized to be a longevity determinant, but the evidence for it is based largely on accelerated aging phenotypes of DNA repair mutants. Here, using a panel of 18 rodent species with diverse lifespans, we show that more robust DNA double-strand break (DSB) repair, but not nucleotide excision repair (NER), coevolves with longevity. Evolution of NER, unlike DSB, is shaped primarily by sunlight exposure. We further show that the capacity of the SIRT6 protein to promote DSB repair accounts for a major part of the variation in DSB repair efficacy between short- and long-lived species. We dissected the molecular differences between a weak (mouse) and a strong (beaver) SIRT6 protein and identified five amino acid residues that are fully responsible for their differential activities. Our findings demonstrate that DSB repair and SIRT6 have been optimized during the evolution of longevity, which provides new targets for anti-aging interventions.

Hepatitis E virus and Klebsiella pneumoniae co-infection detected by metagenomics next-generation sequencing in a patient with central nervous system and bloodstream Infection: a case report.

BACKGROUND: Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide with major prevalence in the developing countries and can cause extrahepatic disease including the nervous system. Central nervous system infections caused by HEV are rare and caused by HEV together with other bacteria are even rarer. CASE PRESENTATION: A 68-year-old man was admitted to the hospital due to a headache lasting for 6 days and a fever for 3 days. Lab tests showed significantly raised indicators of inflammation, cloudy cerebrospinal fluid, and liver dysfunction. Hepatitis E virus and Klebsiella pneumoniae were identified in the blood and cerebrospinal fluid using metagenomic next-generation sequencing. The patient received meropenem injection to treat K. pneumoniae infection, isoglycoside magnesium oxalate injection and polyene phosphatidylcholine injection for liver protection. After ten days of treatment, the patient improved and was discharged from the hospital. CONCLUSION: Metagenomic next-generation sequencing, which can detect various types of microorganisms, is powerful for identifying complicated infections.

Fast quinazolinone synthesis by combining enzymatic catalysis and photocatalysis.

A fast and highly efficient method for the synthesis of functionalized quinazolinones by combining enzymatic catalysis and photocatalysis is reported. The α-Chymotrypsin catalyzed the cyclization of aldehyde and 2-aminobenzamide, which was subsequently followed by White LED-induced oxidation of 2-phenyl-2, 3-dihydroquinazolin-4(1H)-one to obtain quinazolinone. The reaction process was highly efficient with a reaction yield of 99% in just 2 h, and a wide range of quinazolinones could be synthesized. Furthermore, the plausible mechanism was investigated by control experiments and DFT calculations. This protocol provides an alternative synthetic route for the preparation of quinazolinone derivatives.

Synthesis of quinazoline by decarboxylation of 2-aminobenzylamine and α-keto acid under visible light catalysis.

Quinazoline compounds demonstrate a variety of physiological and pharmacological activities. However, the most common syntheses require large quantities of oxidants, high temperature, and other extreme conditions. In this study, quinazoline compounds were synthesized from the condensation of α-keto acid and 2-aminobenzylamine and then decarboxylation under blue LED irradiation at room temperature without transition metal catalysts or additives. Therefore, we demonstrated that by using α-keto acid as the acyl source, decarboxylation can be realized under blue LED without oxidants, in a simple, mild, and environmentally friendly process.

Cooperation promotes the evolution of separate sexes from hermaphrodites with unitary growth.

Most animals have specialized into separate sexes but most plants remain hermaphroditic. The underlining cause for this is still unclear. Here we address this question by evolutionary stable strategy analysis and exact calculation of frequency-dependent selection and genetic drift in geographically structured populations. Reproductive investments of hermaphrodites are divided into male and female functions, and each sex requires linear investments that increase linearly with successful gamete number and reusable investments (RIs) that increase less than linearly. Individuals specializing into one sex require RIs of only this sex and thus can produce more gametes. However, these gametes suffer strong kin competition as they are of the same sex and gamete number of the other sex decreases. The success of individuals specializing into one sex requires individuals specializing into the other sex to cooperate with them, providing them with more opposite-sex gametes and relaxing them of the same-sex competition. The evolution of this cooperation does not require two rare mutations to happen simultaneously at the same place, because single-sex mutants can sparsely spread in a hermaphroditic population with RIs despite genetic drift and wait for mutants of the other sex to arise. RI resembles fixed cost in previous theories. However, previous theories considered all costs except for costs for gametes as fixed costs and this does not capture an important plant-animal difference; modular growth of sexual organs in most plants and some animals promotes reproductive investments to increase linearly with offspring number, so their investments in sexual organs are linear investments rather than fixed costs. This study shows the evolution of separate sexes from hermaphrodites as an example of the evolution of cooperation and mutualism as in harmony games, and highlights modular growth as an important factor that prevents most plants and some animals from evolving into separate sexes.

Fern-like Plants Establishing the Understory of the Late Devonian Xinhang Lycopsid Forest.

Forests appeared during the Middle to Late Devonian, but Devonian forests and their compositions are still rarely known. Xinhang forest was reported as the largest Devonian forest, with lycopsid trees of Guangdedendron micrum Wang et al. A fern-like plant Xinhangia spina Yang and Wang with shoots and anatomy, was previously described from this forest, but its habit and ecology remain unclear. From Xinhang forest, we now report more specimens of fern-like plants including X. spina and some unnamed plants in several beds. Prominent adventitious roots, spines and secondary xylem indicate that the stems of X. spina are largely procumbent to function as anchorage, absorption and support. Other fern-like plants with distinct roots or multiple slender branches also suggest procumbent habits. Xinhang forest is thus reconsidered as multispecific with a canopy of lycopsid trees and understory of diverse fern-like plants, which are adapted to the disturbed coastal environment. The composition of Xinhang forest may indicate a structural transition of the early forests' dominator from fern-like plants to lycopsids.

N-Heterocyclic imine-based bis-gallium(I) carbene analogs featuring a four-membered Ga2N2 ring.

A combination of Ga(I) centers as important building blocks and scaffolds containing N-heterocyclic imines gives new insights into low-valent Ga chemistry. In this study, a mixture of LDipNLi (LDip = 1,3-bis(2,6-diisopropylphenyl)-imidazolin-2-ylidene), tBuOK, and Cp*Ga (Cp* = pentamethylcyclopentadienyl) in toluene afforded [LDipN-Ga]2 (1) via salt metathesis. X-ray structure analysis of 1 revealed a four-membered Ga2N2 ring, and DFT studies indicated the presence of a lone pair at each Ga center. In addition, compound 1 demonstrated diverse reactivities towards methyl trifluoromethanesulfonate, diphenyl disulfide, 9,10-phenanthrenequinone, and ECl2 (E = Ge or Sn).

A New Fern-like Plant Xinhangia spina Gen. et sp. Nov. from the Upper Devonian of China.

Palaeozoic fern-like plants show great diversity in their morphology and/or anatomy. Within this group, a novel taxon, Xinhangia spina gen. et sp. nov., is now reported from the Upper Devonian (Famennian) Wutong Formation of Anhui Province, China. The primary and secondary branches are borne alternately and sometimes in a triseriate pattern. Spines are evident on the main axes or stems and on the primary branches. Vegetative ultimate appendages with recurved tips are alternate, usually dichotomous 1-2 times, and sometimes as an aphlebia located at the base of primary or secondary branches. Fertile ultimate appendages are alternate, usually dichotomous 1-2 times, and terminate in elongated and paired sporangia. The stele has a clepsydroid-like primary xylem with each end bearing a protoxylem strand. The secondary xylem surrounding the primary xylem illustrates uniseriate rays. With rare divisions in both the vegetative and fertile ultimate appendages, Xinhangia represents a morphologically primitive plant. It is of uncertain affinity at the class or order level. The stelar architecture suggests that the clepsydroid stele may not be emphasized in discussing the relationship among fern-like plants such as rhacophytaleans.

Cooperation and the evolution of anisogamy.

In the lights of the concept of cooperation wholes, I discuss why the differentiation of sperm and ova can occur with a mathematical model. Most of Parker's explanations for anisogamy are not completely proper, because it is proved that sperm competition is neither sufficient nor necessary for anisogamy and cooperation to deal with fertilization risks is the real key to understand the evolution of anisogamy. According to the computer simulation results, the transport of gametes between different individuals, risks of the transport, the consequent inequality of sperm and eggs and competition among different individuals were the main causes of gamete differentiation. But these factors have different roles and effects. The transport risk is the main reason for individuals of different mating types to cooperate and differentiate into sperm and egg producers. The transported gametes have an advantage to evolve into sperm to seek for a larger gamete number over the fixed gametes, because they suffer more risks as they can encounter the same fixed gamete and less sibling competition as they can be dispersed better. Gamete competition among different individuals just causes the transported gametes to become as small as possible if they have already become smaller beyond a critical state. In the final discussion, I further put the evolution of anisogamy into a broader background of levels of selection and of the evolution of cooperation, the most important existential mode of matters that makes life as life.

Mitochondrial inverted repeats strongly correlate with lifespan: mtDNA inversions and aging.

Mitochondrial defects are implicated in aging and in a multitude of age-related diseases, such as cancer, heart failure, Parkinson's disease, and Huntington's disease. However, it is still unclear how mitochondrial defects arise under normal physiological conditions. Mitochondrial DNA (mtDNA) deletions caused by direct repeats (DRs) are implicated in the formation of mitochondrial defects, however, mitochondrial DRs show relatively weak (Pearson's r = -0.22, p<0.002; Spearman's ρ = -0.12, p = 0.1) correlation with maximum lifespan (MLS). Here we report a stronger correlation (Pearson's r = -0.55, p<10(-16); Spearman's ρ = -0.52, p<10(-14)) between mitochondrial inverted repeats (IRs) and lifespan across 202 species of mammals. We show that, in wild type mice under normal conditions, IRs cause inversions, which arise by replication-dependent mechanism. The inversions accumulate with age in the brain and heart. Our data suggest that IR-mediated inversions are more mutagenic than DR-mediated deletions in mtDNA, and impose stronger constraint on lifespan. Our study identifies IR-induced mitochondrial genome instability during mtDNA replication as a potential cause for mitochondrial defects.

IGF1R levels in the brain negatively correlate with longevity in 16 rodent species.

The insulin/insulin-like growth factor signaling (IIS) pathway is a major conserved regulator of aging. Nematode, fruit fly and mouse mutants with reduced IIS signaling exhibit extended lifespan. These mutants are often dwarfs leading to the idea that small body mass correlates with longevity within species. However, when different species are compared, larger animals are typically longer-lived. Hence, the role of IIS in the evolution of life history traits remains unresolved. Here we used comparative approach to test whether IGF1R signaling changes in response to selection on lifespan or body mass and whether specific tissues are involved. The IGF1R levels in the heart, lungs, kidneys, and brains of sixteen rodent species with highly diverse lifespans and body masses were measured via immunoblot after epitope conservation analysis. We report that IGF1R levels display strong negative correlation with maximum lifespan only in brain tissue and no significant correlations with body mass for any organ. The brain-IGF1R and lifespan correlation holds when phylogenetic non-independence of data-points is taken into account. These results suggest that modulation of IGF1R signaling in nervous tissue, but not in the peripheral tissues, is an important factor in the evolution of longevity in mammals.