Heterochromatin is a key architectural feature of eukaryotic chromosomes, which endows particular genomic domains with specific functional properties. The capacity of heterochromatin to restrain the activity of mobile elements, isolate DNA repair in repetitive regions and ensure accurate chromosome segregation is crucial for maintaining genomic stability. Nucleosomes at heterochromatin regions display histone post-translational modifications that contribute to developmental regulation by restricting lineage-specific gene expression. The mechanisms of heterochromatin establishment and of heterochromatin maintenance are separable and involve the ability of sequence-specific factors bound to nascent transcripts to recruit chromatin-modifying enzymes. Heterochromatin can spread along the chromatin from nucleation sites. The propensity of heterochromatin to promote its own spreading and inheritance is counteracted by inhibitory factors. Because of its importance for chromosome function, heterochromatin has key roles in the pathogenesis of various human diseases. In this Review, we discuss conserved principles of heterochromatin formation and function using selected examples from studies of a range of eukaryotes, from yeast to human, with an emphasis on insights obtained from unicellular model organisms.

Intelligence — the ability to learn, reason and solve problems — is at the forefront of behavioural genetic research. Intelligence is highly heritable and predicts important educational, occupational and health outcomes better than any other trait. Recent genome-wide association studies have successfully identified inherited genome sequence differences that account for 20% of the 50% heritability of intelligence. These findings open new avenues for research into the causes and consequences of intelligence using genome-wide polygenic scores that aggregate the effects of thousands of genetic variants.

Catalytic anticancer metallodrugs active at low doses could minimize side-effects, introduce novel mechanisms of action that combat resistance and widen the spectrum of anticancer-drug activity. Here we use highly stable chiral half-sandwich organometallic Os(II) arene sulfonyl diamine complexes, [Os(arene)(TsDPEN)] (TsDPEN, N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine), to achieve a highly enantioselective reduction of pyruvate, a key intermediate in metabolic pathways. Reduction is shown both in aqueous model systems and in human cancer cells, with non-toxic concentrations of sodium formate used as a hydride source. The catalytic mechanism generates selectivity towards ovarian cancer cells versus non-cancerous fibroblasts (both ovarian and lung), which are commonly used as models of healthy proliferating cells. The formate precursor N-formylmethionine was explored as an alternative to formate in PC3 prostate cancer cells, which are known to overexpress a deformylase enzyme. Transfer-hydrogenation catalysts that generate reductive stress in cancer cells offer a new approach to cancer therapy.

The recent availability of shale gas has led to a renewed interest in C–H bond activation as the first step towards the synthesis of fuels and fine chemicals. Heterogeneous catalysts based on Ni and Pt can perform this chemistry, but deactivate easily due to coke formation. Cu-based catalysts are not practical due to high C–H activation barriers, but their weaker binding to adsorbates offers resilience to coking. Using Pt/Cu single-atom alloys (SAAs), we examine C–H activation in a number of systems including methyl groups, methane and butane using a combination of simulations, surface science and catalysis studies. We find that Pt/Cu SAAs activate C–H bonds more efficiently than Cu, are stable for days under realistic operating conditions, and avoid the problem of coking typically encountered with Pt. Pt/Cu SAAs therefore offer a new approach to coke-resistant C–H activation chemistry, with the added economic benefit that the precious metal is diluted at the atomic limit.

Any long-lived chemical structure in solution is subject to statistical energy equilibration, so the history of any specific structure does not affect its subsequent reactions. This is not true for very short-lived intermediates because energy equilibration takes time. Here, this idea is applied to achieve the ‘energy labelling’ of a reactive intermediate. The selectivity of the ring-opening α-cleavage reaction of the 1-methylcyclobutoxy radical is found here to vary broadly depending on how the radical was formed. Reactions that provide little excess energy to the intermediate lead to a high selectivity in the subsequent cleavage (measured as a kinetic isotope effect), whereas reactions that provide more excess energy to the intermediate exhibit a lower selectivity. Accounting for the expected excess energy allows the prediction of the observed product ratios and, in turn, the product ratios can be used to determine the energy present in an intermediate.

With the transformation of social patterns, the proportion of female office workers has increased and women have seen a huge increase in purchasing power in the consumer market due to economic independence. From the perspective of the automotive industry, whose main customers were male customers, nowadays, it has changed to designing smaller models, which are more suitable for women to drive. When it comes to a car, men are more focused on horsepower and speed, while women pay more attention to its storage, safety, and easy operation. For female office workers, a car is not only a transportation tool for commutes, but also an assistant that can accompany them shopping and travelling. Therefore, if automotive interiors can meet the usage needs of females, meaning practicality and safety, they can make female drivers feel intimate and comfortable. In order to understand the real needs of female office workers for automotive interiors, in the first phase, this paper adopted case interviews to determine female car-purchasing trends in best-selling automobile manufacturers, as well as their opinions on needs for automotive interiors, which were used as the basis for the questionnaire design. In the second phase,the questionnaire method was used to discuss the life characteristics and needs of female office workers for automotive interiors, and the statistical software SPSS was employed to analyze the differences in needs for automotive interiors among female office workers of different types; and finally, a design principle suitable for this consumer group was concluded. Regarding the results of this paper, automotive interiors are divided into five factors, which are functional storage, spatial aesthetics, digital devices, comfortable feeling, and safety and cleanness. Female office workers are divided into the three groups: (1) The discerning and intellectual pleasure seekers; (2) The regular and easy-going-life seekers; and (3) The modern information seekers. The results show that there are differences in the needs for automotive interiors amongfemaleofficeworkersofdifferenttypes. Tobespecific,group1,thediscerningandintellectual pleasure seekers, who are engaged in the medical and electronics industries, pay the most attention to safety, cleanliness, and digital device needs. Group 2, the regular and easy-going-life seekers, who are engaged in public education, the financial industry, and traditional industries, pay most attention to the needs of comfortable feeling. Group 3, the modern information seekers, who are engaged in service anddesign industries, paymost attention tothe needs offunctional storage, spatial aesthetics, digital devices, safety, and cleanliness.

Compartmentation is essential for the localization of biological processes within a cell. In 2010, three groups independently reported that cytidine triphosphate synthase (CTPS), a metabolic enzyme for de novo synthesis of the nucleotide CTP, is compartmentalized in cytoophidia (Greek for “cellu- larsnakes”)inbacteria,yeast,andfruitflies.Subsequentstudiesdemonstrate that CTPS can also form filaments in human cells. Thus, the cytoophidium represents a new type of intracellular compartment that is strikingly con- served across prokaryotes and eukaryotes. Multiple lines of evidence have recently suggested that polymerization of metabolic enzymes such as CTPS and inosine monophosphate dehydrogenase into filamentous cytoophidia modulates enzymatic activity. With many more metabolic enzymes found to form the cytoophidium and its kind, compartmentation via filamentation may serve as a general mechanism for the regulation of metabolism.

During the last decades, global cyanobacteria biomass increased due to climate change as well as industrial usage for production of biofuels and food supplements. Thus, there is a need for thorough characterization of their potential health risks, including allergenicity. We therefore aimed to identify and characterize similarities in allergenic potential of cyanobacteria originating from the major ecological environments. Different cyanobacterial taxa were tested for immunoreactivity with IgE from allergic donors and non-allergic controls using immunoblot and ELISA. Moreover, mediator release from human FcεR1-transfected rat basophilic leukemia (RBL) cells was measured, allowing in situ examination of the allergenic reaction. Phycocyanin content and IgE-binding potential were determined and inhibition assays performed to evaluate similarities in IgE-binding epitopes. Mass spectrometry analysis identified IgE-reactive bands ranging between 10 and 160 kDa as phycobiliprotein compounds. Levels of cyanobacterial antigen-specific IgE in plasma of allergic donors and mediator release from sensitized RBL cells were significantly higher compared to non-allergic controls (p < 0.01). Inhibition studies indicated cross-reactivity between IgE-binding proteins from fresh water cyanobacteria and phycocyanin standard. We further addressed IgE-binding characteristics of marine water and soil-originated cyanobacteria. Altogether, our data suggest that the intensive use and the strong increase in cyanobacterial abundance due to climate change call for increasing awareness and further monitoring of their potential health hazards.

SUMMARY Lipid rafts are specialized membrane microdomains that function as signaling platforms across plasma membranes of many animal and plant cells. Although there are several studies implicating the role of lipid rafts in capacitation of mammalian sperm, the function of these structures in sperm motility activation and chemotaxis remains unknown. In the ascidian Ciona intestinalis, egg-derived sperm activating- and attracting-factor (SAAF) induces both activation of sperm motility and sperm chemotaxis to the egg. Here we found that a lipid raft disrupter, methyl-b-cyclodextrin (MCD), inhibited both SAAF-induced sperm motility activation and chemotaxis. MCD inhibited both SAAF-promoted synthesis of intracellular cyclic AMP and sperm motility induced by ionophore-mediated Ca2þ entry, but not that induced by valinomycin-mediated hyperpolarization. Ca2þ-imaging revealed that lipid raft disruption inhibited Ca2þ influx upon activation of sperm motility. The Ca2þ-activated adenylyl cyclase was clearly inhibited by MCD in isolated lipid rafts. The results suggest that sperm lipid rafts function in signaling upstream of cAMP synthesis, most likely in SAAF-induced Ca2þ influx, and are required for Ca2þ-dependent pathways underlying activation and chemotaxis in Ciona sperm.

The Eastern Pontides Orogenic Belt offers critical clues on the origin of Early Cenozoic continental arc magmatism in the Alpine-Himalayan system. Systematic geological, geochemical and chronological studies indicate that there are three subgroups among the Early Cenozoic intrusions in the Eastern Pontides Orogenic Belt - Late Paleocene-Early Eocene adakitic intermediate-felsic intrusions, Eocene mafic intrusions, and Eocene non-adakitic granitoid intrusions. Here we focus on the petrology and geodynamic setting of the Eocene non-adakitic granitoid intrusions that are well exposed in a belt between the Thanetian-Ypresian adakitic intrusions in the south and the Lutetian gabbroic intrusions in the north. We also present data on enclaves and surrounding Eocene volcanics. The studied intrusions can be grouped into two main categories, based on their field and petrographical characteristics: granodiorite and monzodiorite-dominated and syenite-dominated bodies. They can be further subdivided into four groups of differing K 2 O content: low-K 2 O (Çevrepınar, Kaletaş, Sarıçiçek and Üzengili), mixed (Sorkunlu, Kozluk and Tamdere), and high-K 2 O (Dölek, Meşebaşı, Çakırbağ and Arslandede) rocks are granodioritic and monzodioritic, whereas shoshonitic (Kösedağ, Meydanlı and Bademli) bodies are syenitic. Zircon U-Pb age determinations reveal that these granitoids were emplaced into crustal rocks of the Eastern Pontides Orogenic Belt between 47 and 42 Ma, in Lutetian time, simultaneously with the gabbroic intrusions in the north. Mineral compositions and P-T calculations are consistent with the interpretation that crustal melting or magma storage started at mid-crustal depth (~ 25 km), with a magma system that subsequently extended to shallow levels (< 4 km). The studied granitoids, enclaves and volcanics exhibit geochemical signatures typical of subduction-related arc magmas, however, the shoshonitic intrusions are younger than most of the other Lutetian intrusions, and indicate a temporal change in arc magmatism. The Sr-Nd-Pb isotopic data indicate that the Lutetian rocks are mixtures of three or four end-member compositions. Considering all geological, geochemical and chronological data, we conclude that the Early Cenozoic magmatism was generated by slab window processes related to ridge subduction in a south-dipping subduction zone below the Eastern Pontides Orogenic Belt.