Bypassing genomic imprinting allows seed development

In developing progeny of mammals the two parental genomes are differentially expressed according to imprinting marks, and embryos with only a uniparental genetic contribution die. Gene expression that is dependent on the parent of origin has also been observed in the offspring of flowering plants, and mutations in the imprinting machinery lead to embryonic lethality, primarily affecting the development of the endosperm-a structure in the seed that nourishes the embryo, analogous to the function of the mammalian placenta. Here we have generated Arabidopsis thaliana seeds in which the endosperm is of uniparental, that is, maternal, origin. We demonstrate that imprinting in developing seeds can be bypassed and viable albeit smaller seedlings can develop from seeds lacking a paternal contribution to the endosperm. Bypassing is only possible if the mother is mutant for any of the FIS-class genes, which encode Polycomb group chromatin-modifying factors. Thus, these data provide functional evidence that the action of the FIS complex balances the contribution of the paternal genome. As flowering plants have evolved a special reproduction system with a parallel fusion of two female with two male gametes, our findings support the hypothesis that only with the evolution of double fertilization did the action of the FIS genes become a requirement for seed development. Furthermore, our data argue for a gametophytic origin of endosperm in flowering plants, thereby supporting a hypothesis raised in 1900 by Eduard Strasburger.     

Diurnal modulation of pacemaker potentials and calcium current in the mammalian circadian clock

The central biological clock of the mammalian brain is located in the suprachiasmatic nucleus. This hypothalamic region contains neurons that generate a circadian rhythm on a single-cell basis. Clock cells transmit their circadian timing signals to other brain areas by diurnal modulation of their spontaneous firing rate. The intracellular mechanism underlying rhythm generation is thought to consist of one or more self-regulating molecular loops, but it is unknown how these loops interact with the plasma membrane to modulate the ionic conductances that regulate firing behaviour. Here we demonstrate a diurnal modulation of Ca2+ current in suprachiasmatic neurons. This current strongly contributes to the generation of spontaneous oscillations in membrane potential, which occur selectively during daytime and are tightly coupled to spike generation. Thus, day-night modulation of Ca2+ current is a central step in transducing the intracellular cycling of molecular clocks to the rhythm in spontaneous firing rate.     

Mutations in SIL1 cause Marinesco-Sjögren syndrome, a cerebellar ataxia with cataract and myopathy

SIL1 (also called BAP) acts as a nucleotide exchange factor for the Hsp70 chaperone BiP (also called GRP78), which is a key regulator of the main functions of the endoplasmic reticulum. We found nine distinct mutations that would disrupt the SIL1 protein in individuals with Marinesco-Sj?gren syndrome, an autosomal recessive cerebellar ataxia complicated by cataracts, developmental delay and myopathy. Identification of SIL1 mutations implicates Marinesco-Sj?gren syndrome as a disease of endoplasmic reticulum dysfunction and suggests a role for this organelle in multisystem disorders.     

The Issue of “Closure” in Jagers op Akkerhuis’s Operator Theory

Attempts to define life should focus on the transition from molecules to cells and the “closure” aspects of this event. Rather than classifying existing objects into living and non-living entities I believe the challenge is to understand how the transition from non-life to life can take place, that is, the how the closure in Jagers op Akkerhuis’s hierarchical classification of operators, comes about.     

Subcapsular sinus macrophages in lymph nodes clear lymph-borne viruses and present them to antiviral B cells

Lymph nodes prevent the systemic dissemination of pathogens such as viruses that infect peripheral tissues after penetrating the body's surface barriers. They are also the staging ground of adaptive immune responses to pathogen-derived antigens. It is unclear how virus particles are cleared from afferent lymph and presented to cognate B cells to induce antibody responses. Here we identify a population of CD11b+CD169+MHCII+ macrophages on the floor of the subcapsular sinus (SCS) and in the medulla of lymph nodes that capture viral particles within minutes after subcutaneous injection. Macrophages in the SCS translocated surface-bound viral particles across the SCS floor and presented them to migrating B cells in the underlying follicles. Selective depletion of these macrophages compromised local viral retention, exacerbated viraemia of the host, and impaired local B-cell activation. These findings indicate that CD169+ macrophages have a dual physiological function. They act as innate 'flypaper' by preventing the systemic spread of lymph-borne pathogens and as critical gatekeepers at the lymph-tissue interface that facilitate the recognition of particulate antigens by B cells and initiate humoral immune responses.     

Bottom-up effects of plant diversity on multitrophic interactions in a biodiversity experiment

Biodiversity is rapidly declining, and this may negatively affect ecosystem processes, including economically important ecosystem services. Previous studies have shown that biodiversity has positive effects on organisms and processes across trophic levels. However, only a few studies have so far incorporated an explicit food-web perspective. In an eight-year biodiversity experiment, we studied an unprecedented range of above- and below-ground organisms and multitrophic interactions. A multitrophic data set originating from a single long-term experiment allows mechanistic insights that would not be gained from meta-analysis of different experiments. Here we show that plant diversity effects dampen with increasing trophic level and degree of omnivory. This was true both for abundance and species richness of organisms. Furthermore, we present comprehensive above-ground/below-ground biodiversity food webs. Both above ground and below ground, herbivores responded more strongly to changes in plant diversity than did carnivores or omnivores. Density and richness of carnivorous taxa was independent of vegetation structure. Below-ground responses to plant diversity were consistently weaker than above-ground responses. Responses to increasing plant diversity were generally positive, but were negative for biological invasion, pathogen infestation and hyperparasitism. Our results suggest that plant diversity has strong bottom-up effects on multitrophic interaction networks, with particularly strong effects on lower trophic levels. Effects on higher trophic levels are indirectly mediated through bottom-up trophic cascades.     

Highly effective SNP-based association mapping and management of recessive defects in livestock

The widespread use of elite sires by means of artificial insemination in livestock breeding leads to the frequent emergence of recessive genetic defects, which cause significant economic and animal welfare concerns. Here we show that the availability of genome-wide, high-density SNP panels, combined with the typical structure of livestock populations, markedly accelerates the positional identification of genes and mutations that cause inherited defects. We report the fine-scale mapping of five recessive disorders in cattle and the molecular basis for three of these: congenital muscular dystony (CMD) types 1 and 2 in Belgian Blue cattle and ichthyosis fetalis in Italian Chianina cattle. Identification of these causative mutations has an immediate translation into breeding practice, allowing marker assisted selection against the defects through avoidance of at-risk matings.