A comparison between the transpressional plate boundaries of South Island, New Zealand, and Southern California, USA: the Alpine and San Andreas fault systems

There are clear similarities in structure and tectonics between the Alpine Fault system (AF) of New Zealand’s South Island and the San Andreas Fault system (SAF) of southern California, USA. Both systems are transpressional, with similar right slip and convergence rates, similar onset ages (for the current traces), and similar total offsets. There are also notable differences, including the dips of the faults and their plate-tectonic histories. The crustal structure surrounding the AF and SAF was investigated with active and passive seismic sources along transects known as South Island Geophysical Transect (SIGHT) and Los Angeles Region Seismic Experiment (LARSE), respectively. Along the SIGHT transects, the AF appears to dip moderately southeastward (~50 deg.), toward the Pacific plate (PAC), but along the LARSE transects, the SAF dips vertically to steeply northeastward toward the North American plate (NAM). Away from the LARSE transects, the dip of the SAF changes significantly. In both locations, a midcrustal decollement is observed that connects the plate-boundary fault to thrust faults farther south in the PAC. This decollement allows upper crust to escape collision laterally and vertically, but forces the lower crust to form crustal roots, reaching maximum depths of 44 km (South Island) and 36 km (southern California). In both locations, upper-mantle bodies of high P velocity are observed extending from near the Moho to more than 200-km depth. These bodies appear to be confined to the PAC and to represent oblique downwelling of PAC mantle lithosphere along the plate boundaries

Understanding earthquake hazards in southern California - the "LARSE" project - working toward a safer future for Los Angeles

The Los Angeles region is underlain by a network of active faults, including many that are deep and do not break the Earth’s surface. These hidden faults include the previously unknown one responsible for the devastating January 1994 Northridge earthquake, the costliest quake in U.S. history. So that structures can be built or strengthened to withstand the quakes that are certain in the future, the Los Angeles Region Seismic Experiment (LARSE) is locating hidden earthquake hazards beneath the region to help scientists determine where the strongest shaking will occur

Predominant and novel de novo variants in 29 individuals with ALG13 deficiency: Clinical description, biomarker status, biochemical analysis, and treatment suggestions

Asparagine-linked glycosylation 13 homolog (ALG13) encodes a nonredundant, highly conserved, X-linked uridine diphosphate (UDP)-N-acetylglucosaminyltransferase required for the synthesis of lipid linked oligosaccharide precursor and proper N-linked glycosylation. De novo variants in ALG13 underlie a form of early infantile epileptic encephalopathy known as EIEE36, but given its essential role in glycosylation, it is also considered a congenital disorder of glycosylation (CDG), ALG13-CDG. Twenty-four previously reported ALG13-CDG cases had de novo variants, but surprisingly, unlike most forms of CDG, ALG13-CDG did not show the anticipated glycosylation defects, typically detected by altered transferrin glycosylation. Structural homology modeling of two recurrent de novo variants, p.A81T and p.N107S, suggests both are likely to impact the function of ALG13. Using a corresponding ALG13-deficient yeast strain, we show that expressing yeast ALG13 with either of the highly conserved hotspot variants rescues the observed growth defect, but not its glycosylation abnormality. We present molecular and clinical data on 29 previously unreported individuals with de novo variants in ALG13. This more than doubles the number of known cases. A key finding is that a vast majority of the individuals presents with West syndrome, a feature shared with other CDG types. Among these, the initial epileptic spasms best responded to adrenocorticotropic hormone or prednisolone, while clobazam and felbamate showed promise for continued epilepsy treatment. A ketogenic diet seems to play an important role in the treatment of these individuals.Fil: Ng, Bobby G.. Sanford Burnham Prebys Medical Discovery Institute; Estados UnidosFil: Eklund, Erik A.. Sanford Burnham Prebys Medical Discovery Institute; Estados Unidos. Lund University; SueciaFil: Shiryaev, Sergey A.. Sanford Burnham Prebys Medical Discovery Institute; Estados UnidosFil: Dong, Yin Y.. University of Oxford; Reino UnidoFil: Abbott, Mary Alice. University of Massachusetts Medical School; Estados UnidosFil: Asteggiano, Carla Gabriela. Universidad Católica de Córdoba; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Bamshad, Michael J.. University of Washington; Estados UnidosFil: Barr, Eileen. University of Emory; Estados UnidosFil: Bernstein, Jonathan A.. University of Stanford; Estados UnidosFil: Chelakkadan, Shabeed. Monash Children's Hospital; AustraliaFil: Christodoulou, John. Sydney Medical School; Australia. University of Melbourne; AustraliaFil: Chung, Wendy K.. Columbia University; Estados UnidosFil: Ciliberto, Michael A.. University of Iowa; Estados UnidosFil: Cousin, Janice. National Human Genome Research Institute ; Estados UnidosFil: Gardiner, Fiona. University of Melbourne; AustraliaFil: Ghosh, Suman. University of Florida; Estados UnidosFil: Graf, William D.. University of Connecticut; Estados UnidosFil: Grunewald, Stephanie. University College London; Estados UnidosFil: Hammond, Katherine. University of Alabama at Birmingahm; Estados UnidosFil: Hauser, Natalie S.. Inova, Fairfax Hospital Falls Church; Estados UnidosFil: Hoganson, George E.. University Of Illinois At Chicago; Estados UnidosFil: Houck, Kimberly M.. Baylor College of Medicine; Estados UnidosFil: Kohler, Jennefer N.. University of Stanford; Estados UnidosFil: Morava, Eva. Mayo Clinic; Estados UnidosFil: Larson, Austin A.. University Of Colorado Anschutz Medical Campus.; Estados UnidosFil: Liu, Pengfei. Baylor Genetics; Estados Unidos. Baylor College Of Medicine; Estados UnidosFil: Madathil, Sujana. University of Iowa; Estados UnidosFil: McCormack, Colleen. University of Stanford; Estados UnidosFil: Meeks, Naomi J.L.. University Of Colorado Anschutz Medical Campus.; Estados UnidosFil: Papazoglu, Gabriela Magali. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentin

Carrying BioMath Education in a Leaky Bucket

In this paper, we describe a project-based mathematical lab implemented in our Applied Mathematics in Biology course. The Leaky Bucket Lab allows students to parameterize and test Torricelli’s law and develop and compare their own alternative models to describe the dynamics of water draining from perforated containers. In the context of this lab students build facility in a variety of applied biomathematical tools and gain confidence in applying these tools in data-driven environments. We survey analytic approaches developed by students to illustrate the creativity this encourages as well as prepare other instructors to scaffold the student learning experience. Pedagogical results based on classroom videography support the notion that the Biology-Applied Math Instructional Model, the teaching framework encompass-ing the lab, is effective in encouraging and maintaining high-level cognition among students. Research-based pedagogical approaches that support the lab are discussed

Spectrum and significance of variants and mutations in the Fanconi anaemia group G gene in children with sporadic acute myeloid leukaemia

Childhood acute myeloid leukaemia (AML) is uncommon. Children with Fanconi anaemia (FA), however, have a very high risk of developing AML. FA is a rare inherited disease caused by mutations in at least 12 genes, of which Fanconi anaemia group G gene (FANCG) is one of the commonest. To address to what extent FANCG variants contribute to sporadic childhood AML, we determined the spectrum of FANCG sequence variants in 107 children diagnosed with sporadic AML, using polymerase chain reaction (PCR), fluorescent single-strand conformational polymorphism (SSCP) and sequencing methodologies. The significance of variants was determined by frequency analysis and assessment of evolutionary conservation. Seven children (6.5%) carried variants in FANCG. Two of these carried two variants, including the known IVS2 + 1G > A mutation with the novel missense mutation S588F, and R513Q with the intronic deletion IVS12-38 (-28)_del11, implying that these patients might have been undiagnosed FA patients. R513Q, which affects a semi-conserved amino acid, was carried in two additional children with AML. Although not significant, the frequency of R513Q was higher in children with AML than unselected cord bloods. While FANCG mutation carrier status does not predispose to sporadic AML, the identification of unrecognised FA patients implies that FA presenting with primary AML in childhood is more common than suspecte