Local Axon Guidance in Cerebral Cortex and Thalamus: Are We There Yet?

Normal brain function requires the development of precise connections between thalamus and cerebral cortex. In this issue of Neuron, Cang et al. and Tori and Levitt argue that EphA/ephrin-A signaling in the target tissue guides sensory thalamic axons to the correct cortical area, and sensory cortical axons to precise thalamic targets. Although EphA/ephrin-A signaling organizes sensory maps within areas, and thalamocortical axons in the internal capsule, both papers argue that each developmental event is dissociable from the others

Evaluating the Impacts of Dam Construction and Longshore Transport upon Modern Sedimentation within the Rio Grande Delta (Texas, U.S.A.)

The modern Rio Grande delta system has experienced a century of dam construction, water removal for irrigation and municipal use, and land use modifications that have dramatically reduced its sediment load. This study examines whether damming has sufficiently limited delivery of upstream sediment to permit locally eroded sources and/or littoral transport along the coast to influence the provenance signal of the Rio Grande delta. Changes in sediment provenance within the Rio Grande’s delta can be detected and quantified by measurement of detrital zircon Uranium–lead dating age distributions. Previous provenance studies indicate that modern Rio Grande river sand upstream of Falcon Dam is enriched in zircon derived from Oligocene volcanic fields within the southern Rocky Mountains and the Sierra Madre Occidental. Results from this study indicate that the abundance of Oligocene zircon is depleted in the modern Rio Grande delta relative to river sand sampled upstream of Falcon Dam. Mixing calculations performed with age distributions representative of Eocene– Miocene fluvial sedimentary deposits that crop out downstream of the dam indicate that erosional reworking of these materials has significantly altered sedimentary provenance within the delta. The importance of north-directed longshore transport along the Mexican (Tamaulipas-Veracruz) Gulf Coast was also evaluated. The absence of distinctive zircon from the Trans Mexican volcanic belt and the basement of southern Mexico within the barrier islands of the Rio Grande delta support previous conclusions that sediment transport along the Tamaulipas-Veracruz shelf is highly compartmentalized and restricted in lateral movement due to seasonal variation in littoral current polarity, topographic barriers along the shelf, and other phenomena. Nevertheless, the results of this study demonstrate that construction of dams across rivers such as the Rio Grande is capable of sufficiently limiting upstream sediment transport to permit otherwise unimportant local sources to dominate sand provenance within their delta systems

Ursinus College Alumni Journal, February 1951

President\u27s page • Five sons and daughters of alumni members of 1954 class at Ursinus • Dr. Miller to present 10-week course on TV • Lt. Governor L. H. Wood takes Harrisburg office • 16 receive degrees on Founders\u27 Day • Dr. Jessie Greaves named distinguished daughter • York alumni show Noss film as scholarship benefit • American Magazine spotlights Isabelle Barr • Ursinus ivy at Cedar Crest • Glassmoyer resigns as journal editor • Memorable Old Timers\u27 Day enjoyed by many • New York association elects Rev. N. Alexander • Ursinus Women\u27s Club holds annual luncheon • Arvanitis to do research on heart-lung machine • Alumni plan fund benefit at Ursinus • Dr. G. E. Pfahler named to alumni presidency • Alumni prominent in church pageant • 1950-51 committees are appointed • Bomberger leads Ursinus through its early years • Sports review: Bruin Grapplers face fair season; Seedersmen off to high scoring start in 1950-51 campaign; Soccer team winless, ties alumni 2-2; Hockeyites take five, Vadner on all-college; Eleven tabs two wins, frosh play big role • Necrology • News about ourselveshttps://digitalcommons.ursinus.edu/alumnijournal/1040/thumbnail.jp

Ursinus College Alumni Journal, May 1951

President\u27s page • Lloyd H. Wood, \u2725, inaugurated as Pennsylvania\u27s Lt. Governor • Dr. H. A. Cochran, of Temple, to address graduating class • Ursinus to be honored by Newcomen Society • Russian DP starts new life at Ursinus • Artist to glorify queen in May Day pageant • Catalogue re-designed • Program completed for 1951 Alumni Day • Dinner held for seniors • Scholarship fund benefit proceeds total $1700 • Marjorie Trayes becomes Rutger\u27s Dean on July 1 • Crossley first reported casualty from Ursinus • Rhea D. Johnson retires • Laucks antique collection near museum proportions • Mack Trucks, Inc., head sets great 1950 record • First Ursinus faculty, courses are selected • Sports review: New candidates display promise as varsity nine posts 3-6 record; Undefeated in 3 years, Helfferich takes MAC award; Slim holdover track squad greets Gurzynski; Alumnae continue active in Philadelphia area sports; Court team winds up successful season with 10 wins in 18 games; Dr. Miller selected as new Ursinus tennis coach; Mermaids drop seven, veteran \u2752 squad sure; Top sports record goes to girls\u27 basketball team; Ursinus\u27 1910 team and the same players today • Obituary • News about ourselveshttps://digitalcommons.ursinus.edu/alumnijournal/1041/thumbnail.jp

DMRT5, DMRT3, and EMX2 Cooperatively Repress at the Pallium-Subpallium Boundary to Maintain Cortical Identity in Dorsal Telencephalic Progenitors

Specification of dorsoventral regional identity in progenitors of the developing telencephalon is a first pivotal step in the development of the cerebral cortex and basal ganglia. Previously, we demonstrated that the two zinc finger doublesex and mab-3 related (Dmrt) genes, Dmrt5 (Dmrta2) and Dmrt3, which are coexpressed in high caudomedial to low rostrolateral gradients in the cerebral cortical primordium, are separately needed for normal formation of the cortical hem, hippocampus, and caudomedial neocortex. We have now addressed the role of Dmrt3 and Dmrt5 in controlling dorsoventral division of the telencephalon in mice of either sex by comparing the phenotypes of single knock-out (KO) with double KO embryos and by misexpressing Dmrt5 in the ventral telencephalon. We find that DMRT3 and DMRT5 act as critical regulators of progenitor cell dorsoventral identity by repressing ventralizing regulators. Early ventral fate transcriptional regulators expressed in the dorsal lateral ganglionic eminence, such as Gsx2, are upregulated in the dorsal telencephalon of Dmrt3;Dmrt5 double KO embryos and downregulated when ventral telencephalic progenitors express ectopic Dmrt5. Conditional overexpression of Dmrt5 throughout the telencephalon produces gene expression and structural defects that are highly consistent with reduced GSX2 activity. Further, Emx2;Dmrt5 double KO embryos show a phenotype similar to Dmrt3;Dmrt5 double KO embryos, and both DMRT3, DMRT5 and the homeobox transcription factor EMX2 bind to a ventral telencephalon-specific enhancer in the Gsx2 locus. Together, our findings uncover cooperative functions of DMRT3, DMRT5, and EMX2 in dividing dorsal from ventral in the telencephalon. SIGNIFICANCE STATEMENT We identified the DMRT3 and DMRT5 zinc finger transcription factors as novel regulators of dorsoventral patterning in the telencephalon. Our data indicate that they have overlapping functions and compensate for one another. The double, but not the single, knock-out produces a dorsal telencephalon that is ventralized, and olfactory bulb tissue takes over most remaining cortex. Conversely, overexpressing Dmrt5 throughout the telencephalon causes expanded expression of dorsal gene determinants and smaller olfactory bulbs. Furthermore, we show that the homeobox transcription factor EMX2 that is coexpressed with DMRT3 and DMRT5 in cortical progenitors cooperates with them to maintain dorsoventral patterning in the telencephalon. Our study suggests that DMRT3/5 function with EMX2 in positioning the pallial-subpallial boundary by antagonizing the ventral homeobox transcription factor GSX2

Lateral thalamic eminence – a novel origin for mGluR1/lot cells

A unique population of cells, called "lot cells," circumscribes the path of the lateral olfactory tract (LOT) in the rodent brain and acts to restrict its position at the lateral margin of the telencephalon. Lot cells were believed to originate in the dorsal pallium (DP). We show that Lhx2 null mice that lack a DP show a significant increase in the number of mGluR1/lot cells in the piriform cortex, indicating a non-DP origin of these cells. Since lot cells present common developmental features with Cajal-Retzius (CR) cells, we analyzed Wnt3a- and Dbx1-reporter mouse lines and found that mGluR1/lot cells are not generated in the cortical hem, ventral pallium, or septum, the best characterized sources of CR cells. Finally, we identified a novel origin for the lot cells by combining in utero electroporation assays and histochemical characterization. We show that mGluR1/lot cells are specifically generated in the lateral thalamic eminence and that they express mitral cell markers, although a minority of them express DeltaNp73 instead. We conclude that most mGluR1/lot cells are prospective mitral cells migrating to the accessory olfactory bulb (OB), whereas mGluR1+, DeltaNp73+ cells are CR cells that migrate through the LOT to the piriform cortex and the OB

A population of gamma-ray emitting globular clusters seen with the Fermi Large Area Telescope

Globular clusters with their large populations of millisecond pulsars (MSPs) are believed to be potential emitters of high-energy gamma-ray emission. Our goal is to constrain the millisecond pulsar populations in globular clusters from analysis of gamma-ray observations. We use 546 days of continuous sky-survey observations obtained with the Large Area Telescope aboard the Fermi Gamma-ray Space Telescope to study the gamma-ray emission towards 13 globular clusters. Steady point-like high-energy gamma-ray emission has been significantly detected towards 8 globular clusters. Five of them (47 Tucanae, Omega Cen, NGC 6388, Terzan 5, and M 28) show hard spectral power indices $(0.7 < \Gamma <1.4)$ and clear evidence for an exponential cut-off in the range 1.0-2.6 GeV, which is the characteristic signature of magnetospheric emission from MSPs. Three of them (M 62, NGC 6440 and NGC 6652) also show hard spectral indices $(1.0 < \Gamma < 1.7)$, however the presence of an exponential cut-off can not be unambiguously established. Three of them (Omega Cen, NGC 6388, NGC 6652) have no known radio or X-ray MSPs yet still exhibit MSP spectral properties. From the observed gamma-ray luminosities, we estimate the total number of MSPs that is expected to be present in these globular clusters. We show that our estimates of the MSP population correlate with the stellar encounter rate and we estimate 2600-4700 MSPs in Galactic globular clusters, commensurate with previous estimates. The observation of high-energy gamma-ray emission from a globular cluster thus provides a reliable independent method to assess their millisecond pulsar populations that can be used to make constraints on the original neutron star X-ray binary population, essential for understanding the importance of binary systems in slowing the inevitable core collapse of globular clusters.Comment: Accepted for publication in A&A. Corresponding authors: J. Kn\"odlseder, N. Webb, B. Pancraz

Fermi Large Area Telescope Constraints on the Gamma-ray Opacity of the Universe

The Extragalactic Background Light (EBL) includes photons with wavelengths from ultraviolet to infrared, which are effective at attenuating gamma rays with energy above ~10 GeV during propagation from sources at cosmological distances. This results in a redshift- and energy-dependent attenuation of the gamma-ray flux of extragalactic sources such as blazars and Gamma-Ray Bursts (GRBs). The Large Area Telescope onboard Fermi detects a sample of gamma-ray blazars with redshift up to z~3, and GRBs with redshift up to z~4.3. Using photons above 10 GeV collected by Fermi over more than one year of observations for these sources, we investigate the effect of gamma-ray flux attenuation by the EBL. We place upper limits on the gamma-ray opacity of the Universe at various energies and redshifts, and compare this with predictions from well-known EBL models. We find that an EBL intensity in the optical-ultraviolet wavelengths as great as predicted by the "baseline" model of Stecker et al. (2006) can be ruled out with high confidence.Comment: 42 pages, 12 figures, accepted version (24 Aug.2010) for publication in ApJ; Contact authors: A. Bouvier, A. Chen, S. Raino, S. Razzaque, A. Reimer, L.C. Reye

Association of Liver Injury From Specific Drugs, or Groups of Drugs, With Polymorphisms in HLA and Other Genes in a Genome-Wide Association Study

BACKGROUND & AIMS: We performed a genome-wide association study (GWAS) to identify genetic risk factors for drug-induced liver injury (DILI) from licensed drugs without previously reported genetic risk factors. METHODS: We performed a GWAS of 862 persons with DILI and 10,588 population-matched controls. The first set of cases was recruited before May 2009 in Europe (n = 137) and the United States (n = 274). The second set of cases were identified from May 2009 through May 2013 from international collaborative studies performed in Europe, the United States, and South America. For the GWAS, we included only cases with patients of European ancestry associated with a particular drug (but not flucloxacillin or amoxicillin-clavulanate). We used DNA samples from all subjects to analyze HLA genes and single nucleotide polymorphisms. After the discovery analysis was concluded, we validated our findings using data from 283 European patients with diagnosis of DILI associated with various drugs. RESULTS: We associated DILI with rs114577328 (a proxy for A*33:01 a HLA class I allele; odds ratio [OR], 2.7; 95% confidence interval [CI], 1.9-3.8; P = 2.4 × 10-8) and with rs72631567 on chromosome 2 (OR, 2.0; 95% CI, 1.6-2.5; P = 9.7 × 10-9). The association with A*33:01 was mediated by large effects for terbinafine-, fenofibrate-, and ticlopidine-related DILI. The variant on chromosome 2 was associated with DILI from a variety of drugs. Further phenotypic analysis indicated that the association between DILI and A*33:01 was significant genome wide for cholestatic and mixed DILI, but not for hepatocellular DILI; the polymorphism on chromosome 2 was associated with cholestatic and mixed DILI as well as hepatocellular DILI. We identified an association between rs28521457 (within the lipopolysaccharide-responsive vesicle trafficking, beach and anchor containing gene) and only hepatocellular DILI (OR, 2.1; 95% CI, 1.6-2.7; P = 4.8 × 10-9). We did not associate any specific drug classes with genetic polymorphisms, except for statin-associated DILI, which was associated with rs116561224 on chromosome 18 (OR, 5.4; 95% CI, 3.0-9.5; P = 7.1 × 10-9). We validated the association between A*33:01 terbinafine- and sertraline-induced DILI. We could not validate the association between DILI and rs72631567, rs28521457, or rs116561224. CONCLUSIONS: In a GWAS of persons of European descent with DILI, we associated HLA-A*33:01 with DILI due to terbinafine and possibly fenofibrate and ticlopidine. We identified polymorphisms that appear to be associated with DILI from statins, as well as 2 non-drug-specific risk factors