Mutations in lectin complement pathway genes COLEC11 and MASP1 cause 3MC syndrome

3MC syndrome has been proposed as a unifying term encompassing the overlapping Carnevale, Mingarelli, Malpuech and Michels syndromes. These rare autosomal recessive disorders exhibit a spectrum of developmental features, including characteristic facial dysmorphism, cleft lip and/or palate, craniosynostosis, learning disability and genital, limb and vesicorenal anomalies. Here we studied 11 families with 3MC syndrome and identified two mutated genes, COLEC11 and MASP1, both of which encode proteins in the lectin complement pathway (collectin kidney 1 (CL-K1) and MASP-1 and MASP-3, respectively). CL-K1 is highly expressed in embryonic murine craniofacial cartilage, heart, bronchi, kidney and vertebral bodies. Zebrafish morphants for either gene develop pigmentary defects and severe craniofacial abnormalities. Finally, we show that CL-K1 serves as a guidance cue for neural crest cell migration. Together, these findings demonstrate a role for complement pathway factors in fundamental developmental processes and in the etiology of 3MC syndrome.     

Immunoregulatory properties of the cytokine IL-34

Interleukin-34 is a cytokine with only partially understood functions, described for the first time in 2008. Although IL-34 shares very little homology with CSF-1 (CSF1, M-CSF), they share a common receptor CSF-1R (CSF-1R) and IL-34 has also two distinct receptors (PTP-ζ) and CD138 (syndecan-1). To make the situation more complex, IL-34 has also been shown as pairing with CSF-1 to form a heterodimer. Until now, studies have demonstrated that this cytokine is released by some tissues that differ to those where CSF-1 is expressed and is involved in the differentiation and survival of macrophages, monocytes, and dendritic cells in response to inflammation. The involvement of IL-34 has been shown in areas as diverse as neuronal protection, autoimmune diseases, infection, cancer, and transplantation. Our recent work has demonstrated a new and possible therapeutic role for IL-34 as a Foxp3⁺ Treg-secreted cytokine mediator of transplant tolerance. In this review, we recapitulate most recent findings on IL-34 and its controversial effects on immune responses and address its immunoregulatory properties and the potential of targeting this cytokine in human.     

Forecasting Ability of a Periodic Component Extracted from Large‐Cap Index Time Series

We develop a method to extract periodic variations in a time series that are hidden in large non‐periodic and stochastic variations. This method relies on folding the time series many times and allows direct visualization of a hidden periodic component without resorting to any fitting procedure. Applying this method to several large‐cap stock time series in Europe, Japan and the USA yields a component with periodicity of 1 year. Out‐of‐sample tests on these large‐cap time series indicate that this periodic component is able to forecast long‐term (decade) behavior for large‐cap time series. Copyright © 2016 John Wiley & Sons, Ltd.     

Forecast robustness in macroeconometric models

This paper investigates potential invariance of mean forecast errors to structural breaks in the data generating process. From the general forecasting literature, such robustness is expected to be a rare occurrence. With the aid of a stylized macro model we are able to identify some economically relevant cases of robustness and to interpret them economically. We give an interpretation in terms of co‐breaking. The analytical results resound well with the forecasting record of a medium‐scale econometric model of the Norwegian economy.     

Cytochrome P450 2U1, a very peculiar member of the human P450s family

Cytochrome P450 2U1 (CYP2U1) exhibits several distinctive characteristics among the 57 human CYPs, such as its presence in almost all living organisms with a highly conserved sequence, its particular gene organization with only five exons, its major location in thymus and brain, and its protein sequence involving an unusually long N-terminal region containing 8 proline residues and an insert of about 20 amino acids containing 5 arginine residues after the transmembrane helix. Few substrates, including fatty acids, N-arachidonoylserotonin (AS), and some drugs, have been reported so far. However, its biological roles remain largely unknown, even though CYP2U1 mutations have been involved in some pathological situations, such as complicated forms of hereditary spastic paraplegia. These data together with its ability to hydroxylate some fatty acids and AS suggest its possible role in lipid metabolism.     

Melatonin and mitochondrial function during ischemia/reperfusion injury

Ischemia/reperfusion (IR) injury occurs in many organs and tissues, and contributes to morbidity and mortality worldwide. Melatonin, an endogenously produced indolamine, provides a strong defense against IR injury. Mitochondrion, an organelle for ATP production and a decider for cell fate, has been validated to be a crucial target for melatonin to exert its protection against IR injury. In this review, we first clarify the mechanisms underlying mitochondrial dysfunction during IR and melatonin’s protection of mitochondria under this condition. Thereafter, special focus is placed on the protective actions of melatonin against IR injury in brain, heart, liver, and others. Finally, we explore several potential future directions of research in this area. Collectively, the information compiled here will serve as a comprehensive reference for the actions of melatonin in IR injury identified to date and will hopefully aid in the design of future research and increase the potential of melatonin as a therapeutic agent.     

Apolipoprotein M affecting lipid metabolism or just catching a ride with lipoproteins in the circulation?

Apolipoprotein M (apoM) is a novel apolipoprotein found mainly in high-density lipoproteins (HDL). Its function is yet to be defined. ApoM (25 kDa) has a typical lipocalin ?-barrel fold and a hydrophobic pocket. Retinoids bind apoM but with low affinity and may not be the natural ligands. ApoM retains its signal peptide, which serves as a hydrophobic anchor to the lipoproteins. This prevents apoM from being lost in the urine. Approximately 5% of HDL carries an apoM molecule. ApoM in plasma (1 μM) correlates strongly with both low-density lipoprotein (LDL) and HDL cholesterol, suggesting a link to cholesterol metabolism. However, in casecontrol studies, apoM levels in patients with coronary heart disease (CHD) and controls were similar, suggesting apoM levels not to affect the risk for CHD in humans. Experiments in transgenic mice suggested apoM to have antiatherogenic properties; possible mechanisms include increased formation of pre-? HDL, enhanced cholesterol mobilization from foam cells, and increased antioxidant properties. Received 28 November 2008; received after revision 15 December 2008; accepted 16 December 2008     

Functions of reticulons in plants: What we can learn from animals and yeasts

Reticulons (RTNs) are membrane-spanning proteins sharing a typical domain named reticulon homology domain (RHD). RTN genes have been identified in all eukaryotic organisms examined so far, and the corresponding proteins have been found predominantly associated to the endoplasmic reticulum membranes. In animal and yeast, in which knowledge of the protein family is more advanced, RTNs are involved in numerous cellular processes such as apoptosis, cell division and intracellular trafficking. Up to now, a little attention has been paid to their plant counterparts, i.e., RTNLBs. In this review, we summarize the data available for RTNLB proteins and, using the data obtained with animal and yeast models, several functions for RTNLBs in plant cells are proposed and discussed. Received 01 July 2008; received after revision 08 September 2008; accepted 30 September 2008