Levels of Ca\u3csub\u3ev\u3c/sub\u3e1.2 L-Type Ca\u3csup\u3e2+\u3c/sup\u3e Channels Peak in the First Two Weeks in Rat Hippocampus Whereas Ca\u3csub\u3ev\u3c/sub\u3e1.3 Channels Steadily Increase through Development

Influx of calcium through voltage-dependent channels regulates processes throughout the nervous system. Specifically, influx through L-type channels plays a variety of roles in early neuronal development and is commonly modulated by G-protein-coupled receptors such as GABAB receptors. Of the four isoforms of L-type channels, only Cav1.2 and Cav1.3 are predominately expressed in the nervous system. Both isoforms are inhibited by the same pharmacological agents, so it has been difficult to determine the role of specific isoforms in physiological processes. In the present study, Western blot analysis and confocal microscopy were utilized to study developmental expression levels and patterns of Cav1.2 and Cav1.3 in the CA1 region of rat hippocampus. Steady-state expression of Cav1.2 predominated during the early neonatal period decreasing by day 12. Steady-state expression of Cav1.3 was low at birth and gradually rose to adult levels by postnatal day 15. In immunohistochemical studies, antibodies against Cav1.2 and Cav1.3 demonstrated the highest intensity of labeling in the proximal dendrites at all ages studied (P1–72). Immunohistochemical studies on one-week-old hippocampi demonstrated significantly more colocalization of GABAB receptors with Cav1.2 than with Cav1.3, suggesting that modulation of L-type calcium current in early development is mediated through Cav1.2 channels

Spreading in Social Systems: Reflections

In this final chapter, we consider the state-of-the-art for spreading in social systems and discuss the future of the field. As part of this reflection, we identify a set of key challenges ahead. The challenges include the following questions: how can we improve the quality, quantity, extent, and accessibility of datasets? How can we extract more information from limited datasets? How can we take individual cognition and decision making processes into account? How can we incorporate other complexity of the real contagion processes? Finally, how can we translate research into positive real-world impact? In the following, we provide more context for each of these open questions.Comment: 7 pages, chapter to appear in "Spreading Dynamics in Social Systems"; Eds. Sune Lehmann and Yong-Yeol Ahn, Springer Natur

Partial genetic characterization of West Nile virus strains, New York State, 2000.

We analyzed nucleotide sequences from the envelope gene of 11 West Nile (WN) virus strains collected in New York State during the 2000 transmission season to determine whether they differed genetically from each other and from the initial strain isolated in 1999. The complete envelope genes of these strains were amplified by reverse transcription-polymerase chain reaction. The resulting sequences were aligned, the genetic distances were computed, and a phylogenetic tree was constructed. Ten (0.7%) of 1,503 positions in the envelope gene were polymorphic in one or more sequences. The genetic distances were 0.003 or less. WN virus strains circulating in 2000 were homogeneous with respect to one another and to a strain isolated in 1999

Subsurface Cooling Rates and Microstructural Response during Laser Based Metal Additive Manufacturing

Laser powder bed fusion (LPBF) is a method of additive manufacturing characterized by the rapid scanning of a high powered laser over a thin bed of metallic powder to create a single layer, which may then be built upon to form larger structures. Much of the melting, resolidification, and subsequent cooling take place at much higher rates and with much higher thermal gradients than in traditional metallurgical processes, with much of this occurring below the surface. We have used in situ high speed X-ray diffraction to extract subsurface cooling rates following resolidification from the melt and above the β-transus in titanium alloy Ti-6Al-4V. We observe an inverse relationship with laser power and bulk cooling rates. The measured cooling rates are seen to correlate to the level of residual strain borne by the minority β-Ti phase with increased strain at slower cooling rates. The α-Ti phase shows a lattice contraction which is invariant with cooling rate. We also observe a broadening of the diffraction peaks which is greater for the β-Ti phase at slower cooling rates and a change in the relative phase fraction following LPBF. These results provide a direct measure of the subsurface thermal history and demonstrate its importance to the ultimate quality of additively manufactured materials

West Nile virus infection in birds and mosquitoes, New York State, 2000.

West Nile (WN) virus was found throughout New York State in 2000, with the epicenter in New York City and surrounding counties. We tested 3,403 dead birds and 9,954 mosquito pools for WN virus during the transmission season. Sixty-three avian species, representing 30 families and 14 orders, tested positive for WN virus. The highest proportion of dead birds that tested positive for WN virus was in American Crows in the epicenter (67% positive, n=907). Eight mosquito species, representing four genera, were positive for WN virus. The minimum infection rate per 1,000 mosquitoes (MIR) was highest for Culex pipiens in the epicenter: 3.53 for the entire season and 7.49 for the peak week of August 13. Staten Island had the highest MIR (11.42 for Cx. pipiens), which was associated with the highest proportion of dead American Crows that tested positive for WN virus (92%, n=48) and the highest number of human cases (n=10)

CRISPR-Cas9 screens in human cells and primary neurons identify modifiers of C9ORF72 dipeptide-repeat-protein toxicity.

Hexanucleotide-repeat expansions in the C9ORF72 gene are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia (c9ALS/FTD). The nucleotide-repeat expansions are translated into dipeptide-repeat (DPR) proteins, which are aggregation prone and may contribute to neurodegeneration. We used the CRISPR-Cas9 system to perform genome-wide gene-knockout screens for suppressors and enhancers of C9ORF72 DPR toxicity in human cells. We validated hits by performing secondary CRISPR-Cas9 screens in primary mouse neurons. We uncovered potent modifiers of DPR toxicity whose gene products function in nucleocytoplasmic transport, the endoplasmic reticulum (ER), proteasome, RNA-processing pathways, and chromatin modification. One modifier, TMX2, modulated the ER-stress signature elicited by C9ORF72 DPRs in neurons and improved survival of human induced motor neurons from patients with C9ORF72 ALS. Together, our results demonstrate the promise of CRISPR-Cas9 screens in defining mechanisms of neurodegenerative diseases

Seasonal mixed layer depth shapes phytoplankton physiology, viral production, and accumulation in the North Atlantic

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Diaz, B. P., Knowles, B., Johns, C. T., Laber, C. P., Bondoc, K. G. V., Haramaty, L., Natale, F., Harvey, E. L., Kramer, S. J., Bolaños, L. M., Lowenstein, D. P., Fredricks, H. F., Graff, J., Westberry, T. K., Mojica, K. D. A., Haëntjens, N., Baetge, N., Gaube, P., Boss, E., Carlson, C. A., Behrenfeld, M. J., Van Mooy, B. A. S., Bidle, K. D. Seasonal mixed layer depth shapes phytoplankton physiology, viral production, and accumulation in the North Atlantic. Nature Communications, 12(1), (2021): 6634, https://doi.org/10.1038/s41467-021-26836-1.Seasonal shifts in phytoplankton accumulation and loss largely follow changes in mixed layer depth, but the impact of mixed layer depth on cell physiology remains unexplored. Here, we investigate the physiological state of phytoplankton populations associated with distinct bloom phases and mixing regimes in the North Atlantic. Stratification and deep mixing alter community physiology and viral production, effectively shaping accumulation rates. Communities in relatively deep, early-spring mixed layers are characterized by low levels of stress and high accumulation rates, while those in the recently shallowed mixed layers in late-spring have high levels of oxidative stress. Prolonged stratification into early autumn manifests in negative accumulation rates, along with pronounced signatures of compromised membranes, death-related protease activity, virus production, nutrient drawdown, and lipid markers indicative of nutrient stress. Positive accumulation renews during mixed layer deepening with transition into winter, concomitant with enhanced nutrient supply and lessened viral pressure.This work was made possible by NASA’s Earth Science Program in support of the North Atlantic Aerosol and Marine Ecosystem Study (15-RRNES15-0011 and 0NSSC18K1563 to K.D.B.; NNX15AF30G to M.J.B.), as well as with support from the National Science Foundation (OIA-2021032 to K.D.B., OCE-157943 to C.A.C., and OCE-1756254 to B.A.S.V.M.), the Gordon and Betty Moore Foundation (Award# 3789 to K.G.V.B.), and NASA’s Future Investigators in Space Science and Technology program (FINESST; grant #826380 to K.D.B.; graduate support to BD)