The Search for the Sidereal and Solar Diurnal Modulations in the Total MACRO Muon Data Set

We have analyzed 44.3M single muons collected by MACRO from 1991 through 2000 in 2,145 live days of operation. We have searched for the solar diurnal, apparent sidereal, and pseudo-sidereal modulation of the underground muon rate by computing hourly deviations of the muon rate from 6 month averages. We find evidence for statistically significant modulations with the solar diurnal and the sidereal periods. The amplitudes of these modulations are <0.1%, and are at the limit of the detector statistics. The pseudo-sidereal modulation is not statistically significant. The solar diurnal modulation is due to the daily atmospheric temperature variations at 20 km, the altitude of primary cosmic ray interactions with the atmosphere; MACRO is the deepest experiment to report this result. The sidereal modulation is in addition to the expected Compton-Getting modulation due to solar system motion relative to the Local Standard of Rest; it represents motion of the solar system with respect to the galactic cosmic rays toward the Perseus spiral arm.Comment: 18 pages, 8 of which are figures, 1 is a table. Accepted by Phys. Rev.

Current methods to analyze lysosome morphology, positioning, motility and function

Since the discovery of lysosomes more than 70 years ago, much has been learned about the functions of these organelles. Lysosomes were regarded as exclusively degradative organelles, but more recent research has shown that they play essential roles in several other cellular functions, such as nutrient sensing, intracellular signalling and metabolism. Methodological advances played a key part in generating our current knowledge about the biology of this multifaceted organelle. In this review, we cover current methods used to analyze lysosome morphology, positioning, motility and function. We highlight the principles behind these methods, the methodological strategies and their advantages and limitations. To extract accurate information and avoid misinterpretations, we discuss the best strategies to identify lysosomes and assess their characteristics and functions. With this review, we aim to stimulate an increase in the quantity and quality of research on lysosomes and further ground-breaking discoveries on an organelle that continues to surprise and excite cell biologists.Medical Biochemistr

Size Doesn't Matter: Towards a More Inclusive Philosophy of Biology

notes: As the primary author, O’Malley drafted the paper, and gathered and analysed data (scientific papers and talks). Conceptual analysis was conducted by both authors.publication-status: Publishedtypes: ArticlePhilosophers of biology, along with everyone else, generally perceive life to fall into two broad categories, the microbes and macrobes, and then pay most of their attention to the latter. ‘Macrobe’ is the word we propose for larger life forms, and we use it as part of an argument for microbial equality. We suggest that taking more notice of microbes – the dominant life form on the planet, both now and throughout evolutionary history – will transform some of the philosophy of biology’s standard ideas on ontology, evolution, taxonomy and biodiversity. We set out a number of recent developments in microbiology – including biofilm formation, chemotaxis, quorum sensing and gene transfer – that highlight microbial capacities for cooperation and communication and break down conventional thinking that microbes are solely or primarily single-celled organisms. These insights also bring new perspectives to the levels of selection debate, as well as to discussions of the evolution and nature of multicellularity, and to neo-Darwinian understandings of evolutionary mechanisms. We show how these revisions lead to further complications for microbial classification and the philosophies of systematics and biodiversity. Incorporating microbial insights into the philosophy of biology will challenge many of its assumptions, but also give greater scope and depth to its investigations

Large-scale sequencing identifies multiple genes and rare variants associated with Crohn's disease susceptibility

Genome-wide association studies (GWASs) have identified hundreds of loci associated with Crohn's disease (CD). However, as with all complex diseases, robust identification of the genes dysregulated by noncoding variants typically driving GWAS discoveries has been challenging. Here, to complement GWASs and better define actionable biological targets, we analyzed sequence data from more than 30,000 patients with CD and 80,000 population controls. We directly implicate ten genes in general onset CD for the first time to our knowledge via association to coding variation, four of which lie within established CD GWAS loci. In nine instances, a single coding variant is significantly associated, and in the tenth, ATG4C, we see additionally a significantly increased burden of very rare coding variants in CD cases. In addition to reiterating the central role of innate and adaptive immune cells as well as autophagy in CD pathogenesis, these newly associated genes highlight the emerging role of mesenchymal cells in the development and maintenance of intestinal inflammation.Large-scale sequence-based analyses identify novel risk variants and susceptibility genes for Crohn's disease, and implicate mesenchymal cell-mediated intestinal homeostasis in disease etiology.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Forbear is a homophone: Lexical prosody does not constrain lexical access

Contains fulltext : 5943.pdf (publisher's version ) (Open Access)Because stress can occur in any position within an English word, lexical prosody could serve as a minimal distinguishing feature between pairs of words. However, most pairs of English words with stress pattern opposition also differ vocalically: OBject and obJECT, CONtent and conTENT have different vowels in their first syllables as well as different stress patterns. To test whether prosodic information is made use of in auditory word recognition independently of segmental phonetic information, it is necessary to examine pairs like FORbear - forBEAR or TRUSty - trusTEE, semantically unrelated words which exhibit stress pattern opposition but no segmental difference. In a cross-modal priming task, such words produce the priming effects characteristic of homophones, indicating that lexical prosody is not used in the same way as segmental structure to constrain lexical access