To Be or No B2: A Rare Cause of Stridor and Weakness in a Toddler

We present a case of a young child with a rare metabolic disorder whose clinical presentation resembled that of autoimmune myasthenia gravis. The differential diagnosis was expanded when autoantibody testing was negative and the patient did not respond to standard immunomodulatory therapies. Rapid whole genome sequencing identified 2 rare variants of uncertain significance in the SLC52A3 gene shown to be in compound heterozygous state after parental testing. Biallelic mutations in SLC52A3 are associated with Riboflavin Transporter Deficiency, which in its untreated form, results in progressive neurodegeneration and death. Supplementation with oral riboflavin has been shown to limit disease progression and improve symptoms in some patients. When the diagnosis is suspected, patients should be started on supplementation immediately while awaiting results from genetic studies

IMPACT OF THE NORTH AMERICAN MONSOON ON ISOTOPE PALEOALTIMETERS: IMPLICATIONS FOR THE PALEOALTIMETRY OF THE AMERICAN SOUTHWEST

International audiencePaleoaltimetric studies have characterized in detail the relationship between carbonate oxygen isotope ratios (d18Oc) and elevation in orogens with simple, single-moisture-source hydrological systems, and applied this relationship to ancient continental carbonates to provide constraints on their past elevation. However, mixing of different atmospheric moisture sources in low-elevation orogens should affect d18Oc values, but this effect has not yet been confirmed unequivocally. In the American Southwest, summer monsoonal moisture, sourced in the Equatorial Pacific and the Gulf of Mexico, and winter moisture, sourced in the East Pacific, both contribute to annual rainfall. We present stable isotope results from Quaternary carbonates within the American Southwest to characterize the regional d18Oc-elevation relationship. We then provide stable isotope results from local Eocene carbonates to reconstruct late Laramide paleoelevations. The Quaternary d18Oc-elevation relationship in the American Southwest is not as straightforward as in more simple hydrological systems. d18Oc changes with altitude are non-linear, scattered, and display an apparent isotopic lapse rate inversion above 1200 m of elevation. We speculate that decreasing surface temperatures at high altitudes limit the duration of carbonate growth to the summer months, biasing d18Oc values toward higher values typical of the summer monsoon and leading to lapse rate inversion. d18Oc-elevation relationships based on modern water isotope data or distillation models predict paleoelevations that range up to as much as 2 km higher than the modern elevations of 2000 to 2400 m for our late Eocene sites located at the southern edge of the Colorado Plateau. By contrast, our d18Oc-elevation relationship for the American Southwest yields lower paleoelevation estimates. These alternate estimates nonetheless suggest that significant elevation (at least ϳ1 km) had already been attained by the Eocene, but are also compatible with < 1 km of uplift by post-Laramide mechanisms. Our results show the limitations of standard d18Oc-elevation models in complex hydrological systems and suggest that similar mechanisms may have led to summer-biased paleoaltimetry estimates for the initial stages of other orogenies -in the American Southwest and elsewhere

Triple oxygen isotope compositions of globally distributed soil carbonates record widespread evaporation of soil waters

International audienceThe stable isotopic composition of pedogenic carbonates is central to many studies of past climate and topography, providing a basis for our understanding of Earth's terrestrial history. A core assumption of many applications of oxygen isotope values (δ18O) of pedogenic carbonate is that they reflect the d18O value of precipitation (rain/snow). This assumption is violated if soil carbonates form in evaporated soil waters. In this work, we develop a means to identify evaporation in ancient soils using the triple oxygen isotope composition (16O-17O-18O) of pedogenic carbonates. Both theoretical predictions of isotope kinetics during evaporation and studies of triple oxygen isotopes in other geological materials show that the deviation in the relationship between d17O and d18O from a reference line, evaluated using the parameter ∆'17O, is sensitive to evaporation. As a first step in developing the use of ∆'17O in ancient pedogenic carbonates, we report ∆'17O values from 47 near-modern pedogenic carbonate samples from globally distributed environments that vary in aridity (hyper-arid to humid). The ∆'17O values of pedogenic carbonate range from -154 to -60 per meg (as CaCO3, measured via O2, VSMOW-SLAP), corresponding to calculated soil water values of -66 to +27 per meg (VSMOW-SLAP) (using a carbonate-water triple oxygen isotope fractionation exponent of 0.5250 and clumped isotope-derived carbonate growth temperatures). The ∆'17O values indicate that evaporative modification of soil water from which pedogenic carbonate forms is common, especially in arid environments. Arid environments host pedogenic carbonates formed from soil waters ranging from highly to minimally evaporated, while humid environments host pedogenic carbonates formed from waters that are only minimally evaporated. The variability in ∆'17O within environments classified by the same aridity may relate to the fact that pedogenic carbonates record soil conditions only during times of carbonate mineralization, which may deviate from annual conditions. Thus, ∆'17O may be useful in understanding the specific circumstances of pedogenic carbonate formation but may not provide incontrovertible evidence of the magnitude of environmental aridity. Evaporative modification of 18O values of pedogenic carbonates can be detected with ∆'17O, thereby improving estimates of δ18O of unevaporated waters. Our data show that evaporation must be (re)considered for all paleoclimate inferences based on the δ18O of pedogenic carbonate. The addition of ∆'17O will re-energize paleoclimate studies that use (or have avoided using) δ18O of pedogenic carbonate

Synthesis and styrene copolymerization of halogen ring-disubstituted 2-methoxyethyl phenylcyanoacrylates

Novel halogen ring-disubstituted 2-methoxyethyl phenylcyanoacrylates, RPhCH=C(CN)CO2CH2CH2OCH3 (where R is 2,5-dibromo, 3,5-dibromo, 2,3-dichloro, 2,4-dichloro, 2,6-dichloro, 3,4-dichloro, 3,5-dichloro, 2,4-difluoro, 2,5-difluoro, 2,6-difluoro, 3,4-difluoro, 3,5-difluoro, 2-chloro-6-fluoro, 3-chloro-4-fluoro, 2-chloro-5-nitro, 4-chloro-3-nitro, 2-fluoro-5-iodo) were prepared and copolymerized with styrene. The acrylates were synthesized by the piperidine catalyzed Knoevenagel condensation of ring-disubstituted benzaldehydes and 2-methoxyethyl cyanoacetate, and characterized by CHN analysis, IR, 1H and 13C NMR. All the acrylates were copolymerized with styrene in solution with radical initiation (ABCN) at 70C. The compositions of the copolymers were calculated from nitrogen analysis