Low Atlantic hurricane activity in the 1970s and 1980s compared to the past 270 years

Hurricane activity in the North Atlantic Ocean has increased significantly since 1995 (refs 1, 2). This trend has been attributed to both anthropogenically induced climate change and natural variability, but the primary cause remains uncertain. Changes in the frequency and intensity of hurricanes in the past can provide insights into the factors that influence hurricane activity, but reliable observations of hurricane activity in the North Atlantic only cover the past few decades. Here we construct a record of the frequency of major Atlantic hurricanes over the past 270 years using proxy records of vertical wind shear and sea surface temperature (the main controls on the formation of major hurricanes in this region) from corals and a marine sediment core. The record indicates that the average frequency of major hurricanes decreased gradually from the 1760s until the early 1990s, reaching anomalously low values during the 1970s and 1980s. Furthermore, the phase of enhanced hurricane activity since 1995 is not unusual compared to other periods of high hurricane activity in the record and thus appears to represent a recovery to normal hurricane activity, rather than a direct response to increasing sea surface temperature. Comparison of the record with a reconstruction of vertical wind shear indicates that variability in this parameter primarily controlled the frequency of major hurricanes in the Atlantic over the past 270 years, suggesting that changes in the magnitude of vertical wind shear will have a significant influence on future hurricane activity.     

Hereditary parkinsonism with dementia is caused by mutations in ATP13A2, encoding a lysosomal type 5 P-type ATPase

Neurodegenerative disorders such as Parkinson and Alzheimer disease cause motor and cognitive dysfunction and belong to a heterogeneous group of common and disabling disorders. Although the complex molecular pathophysiology of neurodegeneration is largely unknown, major advances have been achieved by elucidating the genetic defects underlying mendelian forms of these diseases. This has led to the discovery of common pathophysiological pathways such as enhanced oxidative stress, protein misfolding and aggregation and dysfunction of the ubiquitin-proteasome system. Here, we describe loss-of-function mutations in a previously uncharacterized, predominantly neuronal P-type ATPase gene, ATP13A2, underlying an autosomal recessive form of early-onset parkinsonism with pyramidal degeneration and dementia (PARK9, Kufor-Rakeb syndrome). Whereas the wild-type protein was located in the lysosome of transiently transfected cells, the unstable truncated mutants were retained in the endoplasmic reticulum and degraded by the proteasome. Our findings link a class of proteins with unknown function and substrate specificity to the protein networks implicated in neurodegeneration and parkinsonism.     

Forecasting Inflation Across Euro Area Countries and Sectors: A Panel VAR Approach

In this paper, we adopt a panel vector autoregressive (PVAR) approach to estimating and forecasting inflation dynamics in four different sectors—industry, services, construction and agriculture—across the euro area and its four largest member states: France, Germany, Italy and Spain. By modelling inflation together with real activity, employment and wages at the sectoral level, we are able to disentangle the role of unit labour costs and profit margins as the fundamental determinants of price dynamics on the supply side. In out‐of‐sample forecast comparisons, the PVAR approach performs well against popular alternatives, especially at a short forecast horizon and relative to standard VAR forecasts based on aggregate economy‐wide data. Over longer forecast horizons, the accuracy of the PVAR model tends to decline relative to that of the univariate alternatives, while it remains high relative to the aggregate VAR forecasts. We show that these findings are driven by the event of the Great Recession. Our qualitative results carry over to a multi‐country extension of the PVAR approach. Copyright © 2016 John Wiley & Sons, Ltd.     

Relation between fibrinolytic activity and prostacyclin generation of atherosclerotic artery and dacron prosthetic graft.

The newly formed tissue of dacron vascular prosthetic grafts implanted in humans demonstrates prostacyclin generation and fibrinolytic activity comparable to that of the atherosclerotic artery in the vicinity. This provides some evidence that both activities important for haemostasis run parallel.     

Identification of mutations in CUL7 in 3-M syndrome

Intrauterine growth retardation is caused by maternal, fetal or placental factors that result in impaired endovascular trophoblast invasion and reduced placental perfusion. Although various causes of intrauterine growth retardation have been identified, most cases remain unexplained. Studying 29 families with 3-M syndrome (OMIM 273750), an autosomal recessive condition characterized by severe pre- and postnatal growth retardation, we first mapped the underlying gene to chromosome 6p21.1 and then identified 25 distinct mutations in the gene cullin 7 (CUL7). CUL7 assembles an E3 ubiquitin ligase complex containing Skp1, Fbx29 (also called Fbw8) and ROC1 and promotes ubiquitination. Using deletion analysis, we found that CUL7 uses its central region to interact with the Skp1-Fbx29 heterodimer. Functional studies indicated that the 3-M-associated CUL7 nonsense and missense mutations R1445X and H1464P, respectively, render CUL7 deficient in recruiting ROC1. These results suggest that impaired ubiquitination may have a role in the pathogenesis of intrauterine growth retardation in humans.     

The DNA helicase BRIP1 is defective in Fanconi anemia complementation group J

The protein predicted to be defective in individuals with Fanconi anemia complementation group J (FA-J), FANCJ, is a missing component in the Fanconi anemia pathway of genome maintenance. Here we identify pathogenic mutations in eight individuals with FA-J in the gene encoding the DEAH-box DNA helicase BRIP1, also called FANCJ. This finding is compelling evidence that the Fanconi anemia pathway functions through a direct physical interaction with DNA.     

MID1, mutated in Opitz syndrome, encodes an ubiquitin ligase that targets phosphatase 2A for degradation.

The gene MID1, the mutation of which causes X-linked Opitz G/BBB syndrome (OS, MIM 300000), encodes a microtubule-associated protein (MAP). We show that mutation of MID1 leads to a marked accumulation of the catalytic subunit of protein phosphatase 2A (PP2Ac), a central cellular regulator. PP2Ac accumulation is caused by an impairment of a newly identified E3 ubiquitin ligase activity of the MID1 protein that normally targets PP2Ac for degradation through binding to its alpha4 regulatory subunit in an embryonic fibroblast line derived from a fetus with OS. Elevated PP2Ac causes hypophosphorylation of MAPs, a pathological mechanism that is consistent with the OS phenotype.     

Replacing the complementarity-determining regions in a human antibody with those from a mouse

The variable domains of an antibody consist of a beta-sheet framework with hypervariable regions (or complementarity-determining regions--CDRs) which fashion the antigen-binding site. Here we attempted to determine whether the antigen-binding site could be transplanted from one framework to another by grafting the CDRs. We substituted the CDRs from the heavy-chain variable region of mouse antibody B1-8, which binds the hapten NP-cap (4-hydroxy-3-nitrophenacetyl caproic acid; KNP-cap = 1.2 microM), for the corresponding CDRs of a human myeloma protein. We report that in combination with the B1-8 mouse light chain, the new antibody has acquired the hapten affinity of the B1-8 antibody (KNP-cap = 1.9 microM). Such 'CDR replacement' may offer a means of constructing human monoclonal antibodies from the corresponding mouse monoclonal antibodies.     

Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia,myelodysplastic syndromes and acute myeloid leukemia

We report here that individuals with Noonan syndrome and juvenile myelomonocytic leukemia (JMML) have germline mutations in PTPN11 and that somatic mutations in PTPN11 account for 34% of non-syndromic JMML. Furthermore, we found mutations in PTPN11 in a small percentage of individuals with myelodysplastic syndrome (MDS) and de novo acute myeloid leukemia (AML). Functional analyses documented that the two most common mutations in PTPN11 associated with JMML caused a gain of function.