Two novel missense mutations in the myelin protein zero gene causes Charcot-Marie-Tooth type 2 and Déjérine-Sottas syndrome

<p>Abstract</p> <p>Background</p> <p>The Charcot-Marie-Tooth (CMT) phenotype caused by mutation in the <it>myelin protein zero (MPZ) </it>gene varies considerably, from early onset and severe forms to late onset and milder forms. The mechanism is not well understood. The myelin protein zero (P₀) mediates adhesion in the spiral wraps of the Schwann cell's myelin sheath. The crystalline structure of the extracellular domain of the myelin protein zero (P₀ex) is known, while the transmembrane and intracellular structure is unknown.</p> <p>Findings</p> <p>One novel missense mutation caused a milder late onset CMT type 2, while the second missense mutation caused a severe early onset phenotype compatible with Déjérine-Sottas syndrome.</p> <p>Conclusions</p> <p>The phenotypic variation caused by different missense mutations in the <it>MPZ </it>gene is likely caused by different conformational changes of the MPZ protein which affects the functional tetramers. Severe changes of the MPZ protein cause dysfunctional tetramers and predominantly uncompacted myelin, i.e. the severe phenotypes congenital hypomyelinating neuropathy and Déjérine-Sottas syndrome, while milder changes cause the phenotypes CMT type 1 and 2.</p

Two novel connexin32 mutations cause early onset X-linked Charcot-Marie-Tooth disease

<p>Abstract</p> <p>Background</p> <p>X-linked Charcot-Marie Tooth (CMT) is caused by mutations in the connexin32 gene that encodes a polypeptide which is arranged in hexameric array and form gap junctions.</p> <p>Methods</p> <p>We describe two novel mutations in the connexin32 gene in two Norwegian families.</p> <p>Results</p> <p>Family 1 had a c.225delG (R75fsX83) which causes a frameshift and premature stop codon at position 247. This probably results in a shorter non-functional protein structure. Affected individuals had an early age at onset usually in the first decade. The symptoms were more severe in men than women. All had severe muscle weakness in the legs. Several abortions were observed in this family. Family 2 had a c.536 G>A (C179Y) transition which causes a change of the highly conserved cysteine residue, i.e. disruption of at least one of three disulfide bridges. The mean age at onset was in the first decade. Muscle wasting was severe and correlated with muscle weakness in legs. The men and one woman also had symptom from their hands.</p> <p>The neuropathy is demyelinating and the nerve conduction velocities were in the intermediate range (25–49 m/s). Affected individuals had symmetrical clinical findings, while the neurophysiology revealed minor asymmetrical findings in nerve conduction velocity in 6 of 10 affected individuals.</p> <p>Conclusion</p> <p>The two novel mutations in the connexin32 gene are more severe than the majority of previously described mutations possibly due to the severe structural change of the gap junction they encode.</p

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

State of the climate in 2018

In 2018, the dominant greenhouse gases released into Earth’s atmosphere—carbon dioxide, methane, and nitrous oxide—continued their increase. The annual global average carbon dioxide concentration at Earth’s surface was 407.4 ± 0.1 ppm, the highest in the modern instrumental record and in ice core records dating back 800 000 years. Combined, greenhouse gases and several halogenated gases contribute just over 3 W m−2 to radiative forcing and represent a nearly 43% increase since 1990. Carbon dioxide is responsible for about 65% of this radiative forcing. With a weak La Niña in early 2018 transitioning to a weak El Niño by the year’s end, the global surface (land and ocean) temperature was the fourth highest on record, with only 2015 through 2017 being warmer. Several European countries reported record high annual temperatures. There were also more high, and fewer low, temperature extremes than in nearly all of the 68-year extremes record. Madagascar recorded a record daily temperature of 40.5°C in Morondava in March, while South Korea set its record high of 41.0°C in August in Hongcheon. Nawabshah, Pakistan, recorded its highest temperature of 50.2°C, which may be a new daily world record for April. Globally, the annual lower troposphere temperature was third to seventh highest, depending on the dataset analyzed. The lower stratospheric temperature was approximately fifth lowest. The 2018 Arctic land surface temperature was 1.2°C above the 1981–2010 average, tying for third highest in the 118-year record, following 2016 and 2017. June’s Arctic snow cover extent was almost half of what it was 35 years ago. Across Greenland, however, regional summer temperatures were generally below or near average. Additionally, a satellite survey of 47 glaciers in Greenland indicated a net increase in area for the first time since records began in 1999. Increasing permafrost temperatures were reported at most observation sites in the Arctic, with the overall increase of 0.1°–0.2°C between 2017 and 2018 being comparable to the highest rate of warming ever observed in the region. On 17 March, Arctic sea ice extent marked the second smallest annual maximum in the 38-year record, larger than only 2017. The minimum extent in 2018 was reached on 19 September and again on 23 September, tying 2008 and 2010 for the sixth lowest extent on record. The 23 September date tied 1997 as the latest sea ice minimum date on record. First-year ice now dominates the ice cover, comprising 77% of the March 2018 ice pack compared to 55% during the 1980s. Because thinner, younger ice is more vulnerable to melting out in summer, this shift in sea ice age has contributed to the decreasing trend in minimum ice extent. Regionally, Bering Sea ice extent was at record lows for almost the entire 2017/18 ice season. For the Antarctic continent as a whole, 2018 was warmer than average. On the highest points of the Antarctic Plateau, the automatic weather station Relay (74°S) broke or tied six monthly temperature records throughout the year, with August breaking its record by nearly 8°C. However, cool conditions in the western Bellingshausen Sea and Amundsen Sea sector contributed to a low melt season overall for 2017/18. High SSTs contributed to low summer sea ice extent in the Ross and Weddell Seas in 2018, underpinning the second lowest Antarctic summer minimum sea ice extent on record. Despite conducive conditions for its formation, the ozone hole at its maximum extent in September was near the 2000–18 mean, likely due to an ongoing slow decline in stratospheric chlorine monoxide concentration. Across the oceans, globally averaged SST decreased slightly since the record El Niño year of 2016 but was still far above the climatological mean. On average, SST is increasing at a rate of 0.10° ± 0.01°C decade−1 since 1950. The warming appeared largest in the tropical Indian Ocean and smallest in the North Pacific. The deeper ocean continues to warm year after year. For the seventh consecutive year, global annual mean sea level became the highest in the 26-year record, rising to 81 mm above the 1993 average. As anticipated in a warming climate, the hydrological cycle over the ocean is accelerating: dry regions are becoming drier and wet regions rainier. Closer to the equator, 95 named tropical storms were observed during 2018, well above the 1981–2010 average of 82. Eleven tropical cyclones reached Saffir–Simpson scale Category 5 intensity. North Atlantic Major Hurricane Michael’s landfall intensity of 140 kt was the fourth strongest for any continental U.S. hurricane landfall in the 168-year record. Michael caused more than 30 fatalities and $25 billion (U.S. dollars) in damages. In the western North Pacific, Super Typhoon Mangkhut led to 160 fatalities and$6 billion (U.S. dollars) in damages across the Philippines, Hong Kong, Macau, mainland China, Guam, and the Northern Mariana Islands. Tropical Storm Son-Tinh was responsible for 170 fatalities in Vietnam and Laos. Nearly all the islands of Micronesia experienced at least moderate impacts from various tropical cyclones. Across land, many areas around the globe received copious precipitation, notable at different time scales. Rodrigues and Réunion Island near southern Africa each reported their third wettest year on record. In Hawaii, 1262 mm precipitation at Waipā Gardens (Kauai) on 14–15 April set a new U.S. record for 24-h precipitation. In Brazil, the city of Belo Horizonte received nearly 75 mm of rain in just 20 minutes, nearly half its monthly average. Globally, fire activity during 2018 was the lowest since the start of the record in 1997, with a combined burned area of about 500 million hectares. This reinforced the long-term downward trend in fire emissions driven by changes in land use in frequently burning savannas. However, wildfires burned 3.5 million hectares across the United States, well above the 2000–10 average of 2.7 million hectares. Combined, U.S. wildfire damages for the 2017 and 2018 wildfire seasons exceeded $40 billion (U.S. dollars)

Norsk klima- og ozonforskning. De første 10 år. Sluttrapport fra Forskningsprogram om klima- og ozonspørsmål (1989-1998).

Norge var relativt tidlig ute med et eget forskningsprogram omkring klima- og ozonspørsmål. Ved starten i 1989 var IPCC-prosessen såvidt kommet i gang. Den interdepartementale klima-utredningen ble gjort i 1989-1990 med statusbeskrivelse av norsk klimaforskning og vurdering av klimaeffekter med hovedvekt på naturgrunnlaget. Programmet startet opp omtrent samtidig med at EU-kommisjonen begynte å støtte europeisk ozonlagsforskning. Dette var før de store europeiske stratosfærekampanjene, som startet i 1991, og omtrent samtidig med den amerikanske flykampanjen i Arktis vinteren 1988-89. Det arktiske ozonhullet hadde på det tidspunkt ikke manifestert seg, men mengden av klor og brom i stratosfæren var stigende og man fryktet at dette kunne få negative konsekvenser, slik som i Antarktis. Målet for Forskningsprogram om klima- og ozonspørsmål var å bidra til forbedrede prognoser for fremtidig global, og hvis mulig, regional klima- og ozonlagsutvikling. Programstyret prioriterte å støtte forskning som kunne bidra til sikrere viten om de fysiske og kjemiske forhold som kan føre til endringer i klimaet eller ozonlaget. I visse tilfeller ble det gitt støtte til effektforskning, med særlig vekt på effekter av endret UV-stråling ved bakken. Forskningsinnsatsen i programmet var tverrfaglig, og programmet bidro til at sterke forskningsmiljøer, f.eks. innen paleoklimatologi og oseanografi, samlet seg og dreiet innsatsen mot klimaforskning. Programmet har uten tvil bidratt mye til å styrke og samle norsk klima- og ozonforskning. Programmet har også bidratt til å sette i gang og samordne norsk forskning på viktige områder, som CO2-balansen mellom atmosfære og hav i Grønlands-, Islands- og Norskehavet. Programmet har gjennomført en rekke seminarer, og dette har bidratt til å knytte forskningsmiljøene ytterligere sammen. Etterhvert som forskningen omkring det fysiske grunnlag for klima- og ozonlagsendringer kom i god gjenge, ble det gjennomført en prioriteringsendring slik at effektforskningen i større grad ble tilgodesett. Etter 1996 ble det foretatt en fokusering av klimadelen av programmet med hovedvekt på regionale klimaendringer. Utfordringene med forebyggelse og tilpasning til klimaforandringer står i dag sentralt på samfunnets dagsorden. Ozonlagsreduksjonen ser ut til å kunne fortsette enda i flere tiår selvom internasjonale avtaler overholdes, bl. a. på grunn av at klimaforandringene kan forsterke ozonnedbrytningen. Langsiktig satsing på klima- og ozonforskning er betimelig og nødvendig for at den politiske responsen skal kunne være kunnskapsdrevet

The Network for the Detection of Atmospheric Composition Change (NDACC): history, status and perspectives

The Network for the Detection of Atmospheric Composition Change (NDACC) is an international global network of more than 90 stations making high-quality measurements of atmospheric composition that began official operations in 1991 after 5 years of planning. Apart from sonde measurements, all measurements in the network are performed by ground-based remote-sensing techniques. Originally named the Network for the Detection of Stratospheric Change (NDSC), the name of the network was changed to NDACC in 2005 to better reflect the expanded scope of its measurements. The primary goal of NDACC is to establish long-term databases for detecting changes and trends in the chemical and physical state of the atmosphere (mesosphere, stratosphere, and troposphere) and to assess the coupling of such changes with climate and air quality. NDACC's origins, station locations, organizational structure, and data archiving are described. NDACC is structured around categories of ground-based observational techniques (sonde, lidar, microwave radiometers, Fourier-transform infrared, UV-visible DOAS (differential optical absorption spectroscopy)-type, and Dobson-Brewer spectrometers, as well as spectral UV radiometers), timely cross-cutting themes (ozone, water vapour, measurement strategies, cross-network data integration), satellite measurement systems, and theory and analyses. Participation in NDACC requires compliance with strict measurement and data protocols to ensure that the network data are of high and consistent quality. To widen its scope, NDACC has established formal collaborative agreements with eight other cooperating networks and Global Atmosphere Watch (GAW). A brief history is provided, major accomplishments of NDACC during its first 25 years of operation are reviewed, and a forward-looking perspective is presented. © 2018 Copernicus GmbH. All rights reserved

An Overview of the SOLVE-THESEO 2000 Campaign

Between November 1999 and April 2000, two major field experiments, the SAGE III Ozone Loss and Validation Experiment (SOLVE) and the Third European Stratospheric Experiment on Ozone (THESEO 2000), collaborated to form the largest field campaign yet mounted to study Arctic ozone loss. This international campaign involved more than 500 scientists from over 20 countries spread across the high and mid-latitudes of the northern hemisphere. The main scientific aims of SOLVE-THESEO 2000 were to study (a) the processes leading to ozone loss in the Arctic vortex and (b) the effect on ozone amounts over northern mid-latitudes. The campaign included satellites, heavy lift balloon launches, 6 different aircraft, ground stations, and scores of ozone-sonde. Campaign activities were principally conducted in 3 intensive measurement phases centered on early December 1999, late January 2000, and early March 2000. Observations made during the campaign showed that temperatures were unusually cold in the polar lower stratosphere over the course of the 1999-2000 winter. These cold temperatures resulted in the formation of extensive polar stratospheric clouds (PSCs) across the Arctic. Heterogeneous chemical reactions on the surfaces of the PSC particles produced high levels of reactive chlorine within the polar vortex by early January. This reactive chlorine catalytically destroyed about 60% of the ozone in a layer near 20 km between late January and mid-March 2000

Observational evidence for chemical ozone depletion over the Arctic in winter 1991-92

Long-term depletion of ozone has been observed since the early 1980s in the Antarctic polar vortex, and morerecently at midlatitudes in both hemispheres, with most of the ozone loss occurring in the lower stratosphere.Insufficient measurements of ozone exist, however, to determine decadal trends in ozone concentration in the Arcticwinter. Several studies of ozone concentrations in the Arctic vortex have inferred that chemical ozone loss hasoccurred; but because natural variations in ozone concentration at any given location can be large, deducinglong-term trends from time series is fraught with difficulties. The approaches used previously have often been indirect,typically relying on relationships between ozone and long-lived tracers. Most recently Manney et al. used such anapproach, based on satellite measurements, to conclude that the observed ozone decrease of about 20% in the lowerstratosphere in February and March 1993 was caused by chemical, rather than dynamical, processes. Here we report theresults of a new approach to calculate chemical ozone destruction rates that allows us to compare ozone concentrationsin specific air parcels at different times, thus avoiding the need to make assumptions about ozone/tracer ratios. For theArctic vortex of the 1991-92 winter we find that, at 20 km altitude, chemical ozone loss occurred only between earlyJanuary and mid February and that the loss is proportional to the exposure to sunlight. The timing and magnitude arebroadly consistent with existing understanding of photochemical ozone-depletion processes

An overview of the SOLVE/THESEO 2000 campaign

International audienceBetween November 1999 and April 2000, two major field experiments, the Stratospheric Aerosol and Gas Experiment (SAGE) III Ozone Loss and Validation Experiment (SOLVE) and the Third European Stratospheric Experiment on Ozone (THESEO 2000), collaborated to form the largest field campaign yet mounted to study Arctic ozone loss. This international campaign involved more than 500 scientists from over 20 countries. These scientists made measurements across the high and middle latitudes of the Northern Hemisphere. The main scientific aims of SOLVE/THESEO 2000 were to study (1) the processes leading to ozone loss in the Arctic vortex and (2) the effect on ozone amounts over northern midlatitudes. The campaign included satellites, research balloons, six aircraft, ground stations, and scores of ozonesondes. Campaign activities were principally conducted in three intensive measurement phases centered on early December 1999, late January 2000, and early March 2000. Observations made during the campaign showed that temperatures were below normal in the polar lower stratosphere over the course of the 1999-2000 winter. Because of these low temperatures, extensive polar stratospheric clouds (PSC) formed across the Arctic. Large particles containing nitric acid trihydrate were observed for the first time, showing that denitrification can occur without the formation of ice particles. Heterogeneous chemical reactions on the surfaces of the PSC particles produced high levels of reactive chlorine within the polar vortex by early January. This reactive chlorine catalytically destroyed about 60% of the ozone in a layer near 20 km between late January and mid-March 2000, with good agreement being found between a number of empirical and modeling studies. The measurements made during SOLVE/THESEO 2000 have improved our understanding of key photochemical parameters and the evolution of ozone-destroying forms of chlorine