Short Line Railroading in the Northeastern United States: Its Relevance and Future in Connecting Industry to the North American Rail Network

Short line railroads are vital links in the North American rail network. To remain profitable and viable they must keep abreast of technological advancement and increase cooperation both amongst themselves and with large railroads. Short line railroads fulfill a need in the market place: efficiently distributing and collecting freight transferred locally, nationally, and abroad. Their health and success are a vital component to the continued economic viability of industry in the American northeast. This paper examines short line railroading in the northeastern United States and its relevance and future in connecting industry to the North American Rail Network. To determine a quality background of the short line railroad industry, extensive research was conducted using a variety of sources. The author’s long time enthusiasm for and knowledge of the railroad industry aided in having a substantial understanding from the beginning. Armed with a decade long accumulated knowledge base allowed for immediate immersion, and knowledge gathering from industry magazines, trade journals, textbooks, databases, websites, insider PowerPoint presentations, and personal interviews with short line railroad executives expanded this knowledge base. Industry executive interviews provided pivot points for continued research, guiding the author further. Research confirmed again and again the importance of short line railroads to industry in the northeastern United States. Faced with road congestion, increased costs, and degraded service levels from large railroads, industry needs short lines to provide access to the North American Rail Network. It also distinctly outlined the importance of entrepreneurial spirit and creativity among short line operators as methods to continued growth. The short line railroad industry materially contributes to the economy of the northeastern United States. Preservation of active freight moving companies is important to industry, and ultimately the public. Growth of short line railroads creates increased competition with trucking companies and provides shippers, even ones not located along a railroad, with alternatives to moving freight. Increased freight transportation efficiencies are important for industry, especially if competitors move to right-to-work states, or overseas, where labor costs are generally lower. The short line railroad industry is substantial and worth studying in an effort to sustain and grow the success. This research provides a clear purpose for local, state, and government funding, private investment, and public support for the continued short line railroad activity in the American northeast

Variants in GCNA, X-linked germ-cell genome integrity gene, identified in men with primary spermatogenic failure

Free PMC article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266742/pdf/nihms-1705620.pdfGEMINI Consortium: Donald F Conrad, Liina Nagirnaja, Kenneth I Aston, Douglas T Carrell, James M Hotaling, Timothy G Jenkins, Rob McLachlan, Moira K O'Bryan, Peter N Schlegel, Michael L Eisenberg, Jay I Sandlow, Emily S Jungheim, Kenan R Omurtag, Alexandra M Lopes, Susana Seixas, Filipa Carvalho, Susana Fernandes, Alberto Barros, João Gonçalves, Iris Caetano, Graça Pinto, Sónia Correia, Maris Laan, Margus Punab, Ewa Rajpert-De Meyts, Niels Jørgensen, Kristian Almstrup, Csilla G Krausz, Keith A Jarvi.Member of GEMINI Consortium: João Gonçalves (INSA), lista completa na pág 1179.Male infertility impacts millions of couples yet, the etiology of primary infertility remains largely unknown. A critical element of successful spermatogenesis is maintenance of genome integrity. Here, we present a genomic study of spermatogenic failure (SPGF). Our initial analysis (n=176) did not reveal known gene-candidates but identifed a potentially signifcant single-nucleotide variant (SNV) in X-linked germ-cell nuclear antigen (GCNA). Together with a larger follow-up study (n=2049), 7 likely clinically relevant GCNA variants were identifed. GCNA is critical for genome integrity in male meiosis and knockout models exhibit impaired spermatogenesis and infertility. Single-cell RNA-seq and immunohistochemistry confrm human GCNA expression from spermatogonia to elongated spermatids. Five identifed SNVs were located in key functional regions, including N-terminal SUMO-interacting motif and C-terminal Spartan-like protease domain. Notably, variant p.Ala115ProfsTer7 results in an early frameshift, while Spartan-like domain missense variants p.Ser659Trp and p.Arg664Cys change conserved residues, likely afecting 3D structure. For variants within GCNA’s intrinsically disordered region, we performed computational modeling for consensus motifs. Two SNVs were predicted to impact the structure of these consensus motifs. All identifed variants have an extremely low minor allele frequency in the general population and 6 of 7 were not detected in>5000 biological fathers. Considering evidence from animal models, germ-cell-specifc expression, 3D modeling, and computational predictions for SNVs, we propose that identifed GCNA variants disrupt structure and function of the respective protein domains, ultimately arresting germ-cell division. To our knowledge, this is the frst study implicating GCNA, a key genome integrity factor, in human male infertility.This study was supported by The Eunice Kennedy Shriver NICHD Grant HD080755 (ANY), the Magee-Womens Research Institute University of Pittsburgh Start Up Fund (ANY), PA DoH Grant SAP4100085736 (ANY), NIH P50 Specialized Center Grant HD096723 (KO, ANY, DC, PNS, KH, and MBE), German Research Foundation Clinical Research Unit ‘Male Germ Cells’ grant DFG CRU326 (FT), National Science Centre in Poland, grants no.: 2017/26/D/NZ5/00789 (AM) and 2015/17/B/NZ2/01157; NCN 2020/37/B/NZ5/00549 (MK), Magee-Womens Research Institute University of Pittsburgh, Faculty Fellowship Award and NICHD T32 HD087194 (JH), GM125812 (MB), GM127569 (MB, JLY, and ANY), NIH R00H090289 (MABE), National Health and Medical Research Council Project grant APP1120356 (MKOB, JAV, and DC), UUKi Rutherford Fund Fellowship (BJH), Estonian Research Council, grants IUT34-12 and PRG1021 (ML), and The Netherlands Organization for Scientifc Research grant no.: 918-15-667 as well as an Investigator Award in Science from the Wellcome Trust grant no.: 209451 (JAV). Computational analysis was supported in part by the University of Pittsburgh Center for Research Computing through the resources provided.info:eu-repo/semantics/publishedVersio