Towards a consistent Oxfordian–Kimmeridgian global boundary: current state of knowledge

New data are presented in relation to the worldwide definition of the Oxfordian/Kimmeridgian boundary, i.e. the base of the Kimmeridgian Stage. This data, mostly acquired in the past decade, supports the 2006 proposal to make the uniform boundary of the stages in the Flodigarry section at Staffin Bay on the Isle of Skye, northern Scotland. This boundary is based on the Subboreal-Boreal ammonite successions, and it is distinguished by the Pictonia flodigarriensis horizon at the base of the Subboreal Baylei Zone, and which corresponds precisely to the base of the Boreal Bauhini Zone. The boundary lies in the 0.16 m interval (1.24–1.08 m) below bed 36 in sections F6 at Flodigarry and it is thus proposed as the GSSP for the Oxfordian/Kimmeridgian boundary. This boundary is recognized also by other stratigraphical data – palaeontological, geochemical and palaeomagnetic (including its well documented position close to the boundary between magnetozones F3n, and F3r which is placed in the 0.20 m interval – 1.28 m to 1.48 m below bed 36 – the latter corresponding to marine magnetic anomaly M26r).The boundary is clearly recognizable also in other sections of the Subboreal and Boreal areas discussed in the study, including southern England, Pomerania and the Peri-Baltic Syneclise, Russian Platform, Northern Central Siberia, Franz-Josef Land, Barents Sea and Norwegian Sea. It can be recognized also in the Submediterranean-Mediterranean areas of Europe and Asia where it correlates with the boundary between the Hypselum and the Bimmamatum ammonite zones. The changes in ammonite faunas at the boundary of these ammonite zones – mostly of ammonites of the families Aspidoceratidae and Oppeliidae – also enables the recognition of the boundary in the Tethyan and Indo-Pacific areas – such as the central part of the Americas (Cuba, Mexico), southern America, and southern parts of Asia. The climatic and environmental changes near to the Oxfordian/Kimmeridgian boundary discussed in the study relate mostly to the European areas. They show that very unstable environments at the end of the Oxfordian were subsequently replaced by more stable conditions representing a generally warming trend during the earliest Kimmeridgian. The definition of the boundary between the Oxfordian and Kimmeridgian as given in this study results in its wide correlation potential and means that it can be recognized in the different marine successions of the World

Autophagy mediates degradation of nuclear lamina

Z.D. is supported by a fellow award from the Leukemia & Lymphoma Society. B.C.C. is supported by career development awards from the Dermatology Foundation, Melanoma Research Foundation, and American Skin Association. S.L.B., P.D.A. and R.M. are supported by NIA P01 grant (P01AG031862). S.L.B. is also supported by NIH R01 CA078831. R.D.G. is supported by R01 GM106023 and the Progeria Research Foundation

Neurodegenerative Diseases and Autophagy

Most neurodegenerative diseases are characterized by the accumulation of aggregated proteins within neurons. These aggregate-prone proteins cause toxicity, a phenomenon that is further exacerbated when there is defective protein clearance. Autophagy is an intracellular clearance pathway that can clear these protein aggregates and has been shown to be beneficial in the treatment of neurodegenerative diseases in a variety of model systems. Here, we introduce the key components of the autophagy machinery and signaling pathways that control this process and discuss the evidence that autophagic flux may be impaired and therefore a contributing factor in neurodegenerative disease pathogenesis. Finally, we review the use of autophagy upregulation as a therapeutic strategy to treat neurodegenerative disorders

Production of {\pi}+ and K+ mesons in argon-nucleus interactions at 3.2 AGeV

First physics results of the BM@N experiment at the Nuclotron/NICA complex are presented on {\pi}+ and K+ meson production in interactions of an argon beam with fixed targets of C, Al, Cu, Sn and Pb at 3.2 AGeV. Transverse momentum distributions, rapidity spectra and multiplicities of {\pi}+ and K+ mesons are measured. The results are compared with predictions of theoretical models and with other measurements at lower energies.Comment: 29 pages, 20 figure

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Structural insight into the formation of lipoprotein-β-barrel complexes

The β-barrel assembly machinery (BAM) inserts outer membrane β-barrel proteins (OMPs) in the outer membrane of Gram-negative bacteria. In Enterobacteriacea, BAM also mediates export of the stress sensor lipoprotein RcsF to the cell surface by assembling RcsF–OMP complexes. Here, we report the crystal structure of the key BAM component BamA in complex with RcsF. BamA adopts an inward-open conformation, with the lateral gate to the membrane closed. RcsF is lodged deep within the lumen of the BamA barrel, binding regions proposed to undergo outward and lateral opening during OMP insertion. On the basis of our structural and biochemical data, we propose a push-and-pull model for RcsF export following conformational cycling of BamA, and provide a mechanistic explanation for how RcsF uses its interaction with BamA to detect envelope stress. Our data also suggest that the flux of incoming OMP substrates is involved in the control of BAM activity

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field