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The kinase Mst1, which acts in the Hippo pathway, controls cell proliferation, differentiation and apoptosis. Junichi Sadoshima and his colleagues show that Mst1 in cardiomyocytes phosphorylates the protein Beclin1 to coordinately suppress autophagy and promote apoptosis, thereby having deleterious effects on the heart. Here we show that Mst1, a proapoptotic kinase, impairs protein quality control mechanisms in the heart through inhibition of autophagy. Stress-induced activation of Mst1 in cardiomyocytes promoted accumulation of p62 and aggresome formation, accompanied by the disappearance of autophagosomes. Mst1 phosphorylated the Thr108 residue in the BH3 domain of Beclin1, which enhanced the interaction between Beclin1 and Bcl-2 and/or Bcl-xL, stabilized the Beclin1 homodimer, inhibited the phosphatidylinositide 3-kinase activity of the Atg14L-Beclin1-Vps34 complex and suppressed autophagy. Furthermore, Mst1-induced sequestration of Bcl-2 and Bcl-xL by Beclin1 allows Bax to become active, thereby stimulating apoptosis. Mst1 promoted cardiac dysfunction in mice subjected to myocardial infarction by inhibiting autophagy, associated with increased levels of Thr108-phosphorylated Beclin1. Moreover, dilated cardiomyopathy in humans was associated with increased levels of Thr108-phosphorylated Beclin1 and signs of autophagic suppression. These results suggest that Mst1 coordinately regulates autophagy and apoptosis by phosphorylating Beclin1 and consequently modulating a three-way interaction among Bcl-2 proteins, Beclin1 and Bax.

Edited by a renowned and much cited chemist, this book covers the whole span of molecular computers that are based on biomolecules. The contributions by all the major scientists in the field provide an excellent overview of the latest developments in this rapidly expanding area. A must-have for all researchers working on this very hot topic. Perfectly complements Molecular and Supramolecular Information Processing, also by Prof. Katz, and available as a two-volume set.

Alternative techniques and tools for analyzing biomolecular networks. With the recent rapid advances in molecular biology, high-throughput experimental methods have resulted in enormous amounts of data that can be used to study biomolecular networks in living organisms. With this development has come recognition of the fact that a complicated living organism cannot be fully understood by merely analyzing individual components. Rather, it is the interactions of components or biomolecular networks that are ultimately responsible for an organism's form and function. This book addresses the import

ABSTRACT Recognizing cryptic species is crucial for understanding global biodiversity. The intertidal snail Littoraria flammea is potentially a cryptic species of L. melanostoma widely distributed in the Northwest Pacific. However, the evidence from traditional morphology and single genetic markers is inconsistent. Our study combined quantitative morphological and whole‐genome molecular data to clarify the phylogenetic relationship of three species (L. flammea, L. aff. melanostoma, and L. melanostoma). Three‐dimensional models of shells revealed significant differences in morphology between L. flammea and L. melanostoma. Neutral SNPs indicated that individuals of L. flammea and L. melanostoma were in different clusters. The ratio of interspecific FST to intraspecific FST between L. flammea and L. melanostoma (16) was much larger than the lowest ratio (2.31) in six published genera with cryptic species in gastropods. Non‐neutral SNPs disclosed divergence in functional genes related to reproduction and protein binding. The morphological and phylogenetic analyses corroborated the transitional status of L. aff. melanostoma. These results confirmed that the L. flammea snails north of the Yangtze River Estuary is a cryptic species of L. melanostoma, and allopatric speciation occurs in the L. melanostoma complex. Our study combined quantitative morphological and genome‐wide molecular data to elucidate the controversial phylogenetic relationships among three species of the Littoraria complex (L. flammea, L. melanostoma, and L. aff. melanostoma) in the Northwest Pacific. Our findings confirm that the L. flammea snails north of the Yangtze River Estuary is a cryptic species of L. melanostoma, and dispersal and vicariance could influence allopatric speciation in the L. melanostoma complex.

Building evolutionary trees can be an excellent way for students to see how different gene sequences or organisms are related to one another. Molecular Evolutionary Genetics Analysis (MEGA) software is a free package that lets anyone build evolutionary trees in a user-friendly setup. There are several options to choose from when building trees from molecular data in MEGA, but the most commonly used are neighbor joining and maximum likelihood, both of which give good estimates on the relationship between different molecular sequences. In this article, we describe how to collect data from GenBank, insert the data into a text editor, import the data into MEGA, and use the dataset to create phylogenetic trees.

Tsetse flies are the sole vectors of human African trypanosomiasis throughout sub-Saharan Africa. Both sexes of adult tsetse feed exclusively on blood and contribute to disease transmission. Notable differences between tsetse and other disease vectors include obligate microbial symbioses, viviparous reproduction, and lactation. Here, we describe the sequence and annotation of the 366-megabase Glossina morsitans morsitans genome. Analysis of the genome and the 12,308 predicted protein–encoding genes led to multiple discoveries, including chromosomal integrations of bacterial (Wolbachia) genome sequences, a family of lactation-specific proteins, reduced complement of host pathogen recognition proteins, and reduced olfaction/chemosensory associated genes. These genome data provide a foundation for research into trypanosomiasis prevention and yield important insights with broad implications for multiple aspects of tsetse biology.

FBW7 acts by affecting apoptosis Loss of the tumour suppressor FBW7 is frequently observed in various types of human cancers, but its mechanism of action as a tumour suppressor remains unclear. Two groups demonstrate that in several cancer types, including ovarian cancer and T-cell leukaemias, the apoptosis regulator MCL1 is targeted for degradation by FBW7. Inuzuka et al . find that this mechanism can determine the response to drugs targeting BCL2 family apoptosis factors, and Wertz et al . show that it is activated during mitotic arrest and determines the response to anti-tubulin chemotherapeutics. Deletion or mutation of FBW7 in patients with cancer can therefore render tumours resistant to these therapies. This is one of two papers demonstrating that in several cancer types including ovarian cancer and T-cell leukaemias, the apoptosis regulator MCL1 is targeted for degradation by the FBW7 tumour suppressor. This study finds that this mechanism can determine the response to drugs targeting BCL2 family apoptosis factors. Deletion or mutation of FBW7 found in cancer patients therefore can render tumours resistant to these therapies. The effective use of targeted therapy is highly dependent on the identification of responder patient populations. Loss of FBW7 , which encodes a tumour-suppressor protein, is frequently found in various types of human cancer, including breast cancer, colon cancer 1 and T-cell acute lymphoblastic leukaemia (T-ALL) 2 . In line with these genomic data, engineered deletion of Fbw7 in mouse T cells results in T-ALL 3 , 4 , 5 , validating FBW7 as a T-ALL tumour suppressor. Determining the precise molecular mechanisms by which FBW7 exerts antitumour activity is an area of intensive investigation. These mechanisms are thought to relate in part to FBW7-mediated destruction of key proteins relevant to cancer, including Jun 6 , Myc 7 , cyclin E 8 and notch 1 (ref. 9 ), all of which have oncoprotein activity and are overexpressed in various human cancers, including leukaemia. In addition to accelerating cell growth 10 , overexpression of Jun, Myc or notch 1 can also induce programmed cell death 11 . Thus, considerable uncertainty surrounds how FBW7-deficient cells evade cell death in the setting of upregulated Jun, Myc and/or notch 1. Here we show that the E3 ubiquitin ligase SCF FBW7 (a SKP1–cullin-1–F-box complex that contains FBW7 as the F-box protein) governs cellular apoptosis by targeting MCL1, a pro-survival BCL2 family member, for ubiquitylation and destruction in a manner that depends on phosphorylation by glycogen synthase kinase 3. Human T-ALL cell lines showed a close relationship between FBW7 loss and MCL1 overexpression. Correspondingly, T-ALL cell lines with defective FBW7 are particularly sensitive to the multi-kinase inhibitor sorafenib but resistant to the BCL2 antagonist ABT-737. On the genetic level, FBW7 reconstitution or MCL1 depletion restores sensitivity to ABT-737, establishing MCL1 as a therapeutically relevant bypass survival mechanism that enables FBW7 -deficient cells to evade apoptosis. Therefore, our work provides insight into the molecular mechanism of direct tumour suppression by FBW7 and has implications for the targeted treatment of patients with FBW7 -deficient T-ALL.

Elementary processes in astrophysical environments traditionally attract researchers’ attention. We present the data needed for the inclusion of the specific atomic collisional processes in the investigation of the optical and kinetic properties of weakly ionized stellar atmosphere layers. The first type of processes are collisional ionisation (chemi-ionization) processes, and the second ones are excitation and de-excitation (i.e., ( n - n ′ )-mixing processes). We give the rate coefficients of the aforementioned processes for the conditions that exist in the solar photosphere, the atmosphere of DB white dwarfs, M-type red dwarfs, etc.

Genomes with influence More than 300 labs worldwide are using the fungus Aspergillus nidulans as a model system for molecular genetics, and other species of this fungus are important in everyday life. A package of three genomics papers in this issue covers the Aspergillus field comprehensively. Galagan et al . report the genome sequence of the laboratory classic A. nidulans , and Nierman et al . have sequenced A. fumigatus , known chiefly as a human pathogen and allergen. And finally Machida et al . present genome sequencing and analysis of A. oryzae , focusing in particular on the expansion of genes in its genome, which is almost 25% bigger than the other two genomes. A. oryzae is used in traditional Chinese and Japanese food fermentation (think soy sauce) and also in enzyme production by biotechnologists. Aspergillus fumigatus is exceptional among microorganisms in being both a primary and opportunistic pathogen as well as a major allergen 1 , 2 , 3 . Its conidia production is prolific, and so human respiratory tract exposure is almost constant 4 . A. fumigatus is isolated from human habitats 5 and vegetable compost heaps 6 , 7 . In immunocompromised individuals, the incidence of invasive infection can be as high as 50% and the mortality rate is often about 50% (ref. 2 ). The interaction of A. fumigatus and other airborne fungi with the immune system is increasingly linked to severe asthma and sinusitis 8 . Although the burden of invasive disease caused by A. fumigatus is substantial, the basic biology of the organism is mostly obscure. Here we show the complete 29.4-megabase genome sequence of the clinical isolate Af293, which consists of eight chromosomes containing 9,926 predicted genes. Microarray analysis revealed temperature-dependent expression of distinct sets of genes, as well as 700 A. fumigatus genes not present or significantly diverged in the closely related sexual species Neosartorya fischeri , many of which may have roles in the pathogenicity phenotype. The Af293 genome sequence provides an unparalleled resource for the future understanding of this remarkable fungus.

It is commonly believed that trees were absent in Scandinavia during the last glaciation and first recolonized the Scandinavian Peninsula with the retreat of its ice sheet some 9000 years ago. Here, we show the presence of a rare mitochondrial DNA haplotype of spruce that appears unique to Scandinavia and with its highest frequency to the west—an area believed to sustain ice-free refugia during most of the last ice age. We further show the survival of DNA from this haplotype in lake sediments and pollen of Trondelag in central Norway dating back ~10,300 years and ch loro plast DNA of pine and spruce in lake sediments adjacent to the ice-free Andeya refugium in northwestern Norway as early as ~22,000 and 17,700 years ago, respectively. Our findings imply that conifer trees survived in ice-free refugia of Scandinavia during the last glaciation, challenging current views on survival and spread of trees as a response to climate changes.