180 research outputs found

    Via2G Microtransit Pilot Evaluation

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    Google partnered with Via to launch an on-demand microtransit called Via2G between January and March 2020. The pilot provided employees with free travel to/from two of its offices in suburban, congested Silicon Valley. While the pilot was cut short due to COVID-19, rider participation grew steadily during operation. Of trip requests, 8,636 (87.8%) resulted in a ride offer. Unfulfilled requests were primarily outside of pilot operating times or when rider demand exceeded driver supply. Most users (72%) completed at least two trips, although recurring users were less likely to complete errands on the commute and fewer had a car available for commuting compared to all surveyed Google employees. Prior to Via2G, two-thirds (66%) of survey respondents drove to work at least one day per week, while a plurality (42%) drove five days per week. Compared to non-participants, pilot users were more likely to take ride-hail (14 vs 22 percent) or the Google Bus (24 vs 30 percent) at least once a week prior to the pilot. Recommendations suggest iterations for Google or other centralized employers to consider in future microtransit programs

    Marine Mammals’ NMDA Receptor Structure: Possible Adaptation to High Pressure Environment

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    Divers that are exposed to high pressure (HP) above 1.1 MPa suffer from High Pressure Neurological Syndrome (HPNS), which is implicated with central nervous system (CNS) malfunction. Marine mammals performing extended and deep breath-hold dives are exposed to almost 20 MPa without apparent HPNS symptoms. N-methyl-D-aspartate receptor (NMDAR) has repeatedly been implicated as one of the major factors in CNS hyperexcitability as part of HPNS. Electrophysiological studies in rat brain slices at He HP showed a significant increase in the synaptic NMDAR response, followed by postsynaptic excitability changes. Molecular studies of Rattus norvegicus NMDARs have revealed that different subunit combinations of the NMDAR exhibit different, increased or decreased, current responses under He HP conditions. The purpose of the present research was to disclose if the breath-hold deep diving mammals exhibit NMDAR structural modifications related to HP. We used sequence alignment and homology structure modeling in order to compare deep diving marine mammals’ NMDARs to those of terrestrial mammals. We discovered that deep diving mammals have a special tertiary TMD structure of the GluN2A subunit that differs from that of the terrestrial mammals. In addition, the GluN2A subunit has a group of four conserved a.a. substitutions: V68L (N-terminal domain, NTD) and V440I (agonist-binding domain, ABD) are cetacean specific, E308D (N-terminal domain, NTD) and I816V (transmembrane domain, TMD) were also singularly found in some terrestrial mammals. Since I816V is localized in M4 α-helix region, which is critical for NMDAR activation and desensitization, we hypothesize that the presence of all 4 substitutions rather than a single one, is the combination that may enable HP tolerance. Furthermore, additional special substitutions that were found in the marine mammals’ NTD may affect the Zn2+ binding site, suggesting less or no voltage-independent inhibition by this ion. Our molecular studies of NMDARs containing the GluN2A subunit showed that HP removal of the Zn2+ voltage-independent inhibition could be the mechanism explaining its current increase at HP. Thus, this mechanism could play a crucial role in the CNS hyperexcitability at HP. Less or no voltage-independent Zn2+ inhibition, different conformations of the TMD, and special mutation in the M4 α-helix region of cetaceans’ NMDAR, may give them the advantage they need in order to perform such deep dives without CNS malfunction

    Hawksbill turtles visit moustached barbers: cleaning symbiosis between eretmochelys imbricata and the shrimp stenopus hispidus

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    This seems to be the first record of cleaning symbiosis between marine turtles and shrimps. During their foraging on the reef flat, the turtles regularly visited and posed at the stations. The same stations were visited by a few species of reef fishes, which posed and were cleaned by the shrimps. We suggest that cleaning symbiosis between turtles and shrimps is widespread and went unrecognised due to the superficial resemblance between a resting turtle and a posing and cleaned one. Additionally, we submit a putative origin for the cleaning symbiosis between marine turtles and cleaner shrimps following a few simple behavioural steps.Nas ilhas oceânicas de Fernando de Noronha, ao largo da costa Nordeste do Brasil, registramos tartarugas-de-pente (Eretmochelys imbricata) visitando estações de limpeza mantidas pelo camarão-palhaço (Stenopus hispidus). Este parece ser o primeiro registro de simbiose de limpeza entre tartarugas marinhas e camarões. Durante o seu forrageamento na planície recifal, as tartarugas visitavam e posavam nas estações regularmente. As mesmas estações eram visitadas por algumas espécies de peixes recifais, que aí posavam e eram limpas pelos camarões. Sugerimos aqui que a simbiose de limpeza entre tartarugas marinhas e camarões seja comum e difundida, porém passa despercebida devido à semelhança superficial entre uma tartaruga que esteja descansando e aquela posando e sendo limpa. Além disso, apresentamos uma origem putativa para a simbiose de limpeza entre tartarugas marinhas e camarões-limpadores, que segue etapas comportamentais relativamente simples.1

    Valores hematológicos de tartarugas marinhas Chelonia mydas (Linaeus, 1758) juvenis selvagens do Arquipélago de Fernando de Noronha, Pernambuco, Brasil

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    The hematological reference ranges of sixty wild, apparently health, juvenile green sea turtles (Chelonia mydas) from the Fernando de Noronha Archipelago, Pernambuco State, Brazil, were determined between the months of July and September of 2003. The obtained results were: Packed cell volume 21,4-36,6 %; erythrocytes count 0,244-0,554 x10(6)/µl; Hemoglobin 5,9-14,0 g/dl; Mean Corpuscular Volume 500,4-986,1 fl; Mean Corpuscular Hemoglobin 144,0-367,1 pg; Mean Corpuscular Hemoglobin Concentration 23,7-45,1 g/dl; Total leucocytes count 1178,8-8259,6 /µl; Monocytes 15,4-1494,3 /µl; Lymphocytes 221,1-1924,8 /µl; Heterophils 621,5-4317,8 /µl; Eosinophils 96,1-1831,0 /µl; Basophils 0,0-45,3 /µl; Trombocytes 9513,2-36316,5 /µl. The comparison between the obtained results and literature data reinforce the need to establish hematological counts for specific agglomerations on different geographic and climate conditions, size classes, age, and methodologies. Because of these influences, the values should not be extrapolated to other C. mydas agglomerations and should be used carefully for the clinical evaluation of individuals under other conditions.Foram determinados os valores hematológicos de referência para 60 tartarugas marinhas Chelonia mydas juvenis selvagens aparentemente saudáveis do Arquipélago de Fernando de Noronha, Pernambuco, Brasil nos meses de julho a setembro de 2003. Os resultados obtidos foram: Hematócrito 21,4 a 36,6 %; Hemácias 0,244 a 0,554 x10(6)/µl; Hemoglobina 5,9 a 14,0 g/dl; Volume Corpuscular Médio 500,4 a 986,1 fl; Hemoglobina Corpuscular Média 144,0 a 367,1 pg; Concentração de Hemoglobina Corpuscular Média 23,7 a 45,1 g/dl; Leucócitos 1178,8 a 8259,6 /µl; Monócitos 15,4 a 1494,3 /µl; Linfócitos 221,1 a 1924,8 /µl; Heterófilos 621,5 a 4317,8 /µl; Eosinófilos 96,1 a 1831,0 /µl; Basófilos 0,0 a 45,3 /µl e Trombócitos 9513,2 a 36316,5 /µl. A comparação dos resultados obtidos com os dados da literatura reforça a necessidade do estabelecimento de valores hematológicos específicos para aglomerações em diferentes condições geográficas, climáticas, faixas de tamanho e diferentes metodologias. Devido a estas influências estes valores não devem ser extrapolados para outras aglomerações e devem ser usados com critério para avaliação clínica de indivíduos sob outras condições

    Regulation of Respiration and Apoptosis by Cytochrome c Threonine 58 Phosphorylation

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    Cytochrome c (cytc) is a multifunctional protein, acting as an electron carrier in the electron transport chain (ETC), where it shuttles electrons from bc1 complex to cytochrome c oxidase (COX), and as a trigger of type II apoptosis when released from the mitochondria. We previously showed that cytc is regulated in a highly tissue-specific manner: Cytc isolated from heart, liver, and kidney is phosphorylated on Y97, Y48, and T28, respectively. Here, we have analyzed the effect of a new Cytc phosphorylation site, threonine 58, which we mapped in rat kidney Cytc by mass spectrometry. We generated and overexpressed wild-type, phosphomimetic T58E, and two controls, T58A and T58I cytc; the latter replacement is found in human and testis-specific Cytc. In vitro, COX activity, caspase-3 activity, and heme degradation in the presence of H2o2 were decreased with phosphomimetic Cytc compared to wild-type. Cytc-knockout cells expressing T58E or T58I Cytc showed a reduction in intact cell respiration, mitochondrial membrane potential (∆Ψm), ROS production, and apoptotic activity compared to wild-type. We propose that, under physiological conditions, Cytc is phosphorylated, which controls mitochondrial respiration and apoptosis. Under conditions of stress Cytc phosphorylations are lost leading to maximal respiration rates, ∆Ψm hyperpolarization, ROS production, and apoptosis

    IKK phosphorylates Huntingtin and targets it for degradation by the proteasome and lysosome

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    Expansion of the polyglutamine repeat within the protein Huntingtin (Htt) causes Huntington's disease, a neurodegenerative disease associated with aging and the accumulation of mutant Htt in diseased neurons. Understanding the mechanisms that influence Htt cellular degradation may target treatments designed to activate mutant Htt clearance pathways. We find that Htt is phosphorylated by the inflammatory kinase IKK, enhancing its normal clearance by the proteasome and lysosome. Phosphorylation of Htt regulates additional post-translational modifications, including Htt ubiquitination, SUMOylation, and acetylation, and increases Htt nuclear localization, cleavage, and clearance mediated by lysosomal-associated membrane protein 2A and Hsc70. We propose that IKK activates mutant Htt clearance until an age-related loss of proteasome/lysosome function promotes accumulation of toxic post-translationally modified mutant Htt. Thus, IKK activation may modulate mutant Htt neurotoxicity depending on the cell's ability to degrade the modified species

    Expression and Modulation of LL-37 in Normal Human Keratinocytes, HaCaT cells, and Inflammatory Skin Diseases

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    Defensins and cathelicidins (LL-37) are major antimicrobial peptides (AMPs) of the innate immune system of the human skin. In normal non-inflamed skin these peptides are negligible, but their expression can be markedly increased in inflammatory skin disease such as psoriasis. We designed this study to identify the expressions of LL-37 in normal human keratinocyte (NHK) and HaCaT cells after exposure to stimulants and to investigate difference of LL-37 expression accompanied with cell differentiation status, and come to understand difference of susceptibility to infection in atopic dermatitis and psoriasis. Expressions of LL-37 in NHKs and HaCaT cells were evaluated by using RT-PCR, Western blotting, and immunohistochemical (IHC) staining at 6, 12, and 24 hr post stimulation after exposure to Ultraviolet B irradiation and lipopolysaccharide. And expression of LL-37 in skin biopsy specimens from patients with atopic dermatitis and psoriasis was determined by immunohistochemical analysis. In time-sequential analyses of LL-37 expression revealed that LL-37 was expressed in NHKs, but not in HaCaT cells. IHC analysis confirmed the presence of abundant LL-37 in the epidermis of psoriasis. Therefore we deduced that expression of LL-37 is affected by UV irradiation, bacterial infection, and status of cell differentiation
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