Protein tyrosine phosphatase-1B regulates the tyrosine phosphorylation of the adapter Grb2-associated binder 1 (Gab1) in the retina

Abstract Background Gab1 (Grb2-associated binder 1) is a key coordinator that belongs to the insulin receptor substrate-1 like family of adaptor molecules and is tyrosine phosphorylated in response to various growth factors, cytokines, and numerous other molecules. Tyrosine phosphorylated Gab1 is able to recruit a number of signaling effectors including PI3K, SHP2 and PLC-γ. In this study, we characterized the localization and regulation of tyrosine phosphorylation of Gab1 in the retina. Results Our immuno localization studies suggest that Gab1 is expressed in rod photoreceptor inner segments. We found that hydrogen peroxide activates the tyrosine phosphorylation of Gab1 ex vivo and hydrogen peroxide has been shown to inhibit the protein tyrosine phosphatase PTP1B activity. We found a stable association between the D181A substrate trap mutant of PTP1B and Gab1. Our studies suggest that PTP1B interacts with Gab1 through Tyrosine 83 and this residue may be the major PTP1B target residue on Gab1. We also found that Gab1 undergoes a light-dependent tyrosine phosphorylation and PTP1B regulates the phosphorylation state of Gab1. Consistent with these observations, we found an enhanced Gab1 tyrosine phosphorylation in PTP1B deficient mice and also in retinas treated ex vivo with a PTP1B specific allosteric inhibitor. Conclusions Our laboratory has previously reported that retinas deficient of PTP1B are resistant to light damage compared to wild type mice. Since Gab1 is negatively regulated by PTP1B, a part of the retinal neuroprotective effect we have observed previously in PTP1B deficient mice could be contributed by Gab1 as well. In summary, our data suggest that PTP1B regulates the phosphorylation state of retinal Gab1 in vivo

Business models for enhanced solar photovoltaic (PV) adoption : Transforming customer interaction and engagement practices

Solar energy can play an important role in meeting global energy needs in a sustainable and environmentally friendly manner. However, despite solar energy’s accelerated growth in recent years, its level of diffusion is highly uneven when looked at on a global scale. The solar photovoltaic (PV) companies involved in the sales of PV systems are central to fostering diffusion. A company’s ability to devise and deliver value offerings that match customers’ needs is vital in encouraging the adoption of solar PV technology. The extent to which a company can address market needs and deliver value often depends on the business model it has adopted. The extant research has explored business models based on ownership structures, financing options, the effect of regulatory regimes and policies, industry practices, alliances, and business models for distributed generation and large-scale utility companies. However, the research to date, has mostly neglected the business models of solar companies involved in the sales and installation of solar PV. This qualitative study based on twenty semi-structured interviews contributes to the existing knowledge by exploring how sales and installation companies can enhance solar photovoltaic adoption by transforming customer interactions and engagement practices, which is a key element of a company’s business model. Companies’ ability to communicate value offerings and address consumer concerns is important in enhancing diffusion. The study highlights that transforming customer interaction and engagement practices can help companies broaden customer reach, improve the dissemination of information, reduce transaction costs and efficiently utilise market insights and trends.© 2024 The Authors. Published by Elsevier Ltd on behalf of International Solar Energy Society. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).fi=vertaisarvioitu|en=peerReviewed

Extinction-Induced Aggression in Laboratory Rats

In a study by Azrin et al. (1966), it was found that pigeons attacked other pigeons when the transition from a food reinforcement schedule to an extinction schedule was employed. These aggressive behaviors that appear due to the implementation of an extinction schedule, however, has not been widely studied in the laboratory rat. Examples of the types of phenomena that have been given attention with regard to laboratory rat aggression are male aggression in a mixed-sex colony toward male intruders, attack elicited by the application of aversive stimuli, and female-elicited aggression of male rats living in colonies. The expression of aggressive behaviors in rats appears to be highly responsive to developmental, experiential, and contextual variables. The present study focuses upon aggression displayed toward two characteristically different objects--one a stuffed rat and the other a wood block--when an extinction schedule is employed with laboratory rats. By using an extinction paradigm with rats bar-pressing for food, the present study examines aggression in this context by measuring the intensity and type of aggressive behavior displayed toward the two different objects as well as looking at other behaviors elicited by an extinction schedule

Optimal maps and exponentiation on finite dimensional spaces with Ricci curvature bounded from below

We prove existence and uniqueness of optimal maps on $RCD^*(K,N)$ spaces under the assumption that the starting measure is absolutely continuous. We also discuss how this result naturally leads to the notion of exponentiation. \ua9 2015, Mathematica Josephina, Inc

Marked deterioration in the quality of life of patients with idiopathic pulmonary fibrosis during the last two years of life

BackgroundIdiopathic pulmonary fibrosis (IPF) is a chronic disease with a high symptom burden and poor survival that influences patients' health-related quality of life (HRQOL). We aimed to evaluate IPF patients' symptoms and HRQOL in a well-documented clinical cohort during their last two years of life.MethodsIn April 2015, we sent the Modified Medical Research Council Dyspnea Scale (MMRC), the modified Edmonton Symptom Assessment Scale (ESAS) and a self-rating HRQOL questionnaire (RAND-36) to 300 IPF patients, of which 247 (82%) responded. Thereafter, follow-up questionnaires were sent every six months for two years.ResultsNinety-two patients died by August 2017. Among these patients, HRQOL was found to be considerably low already two years before death. The most prominent declines in HRQOL occurred in physical function, vitality, emotional role and social functioning (pPeer reviewe

Risk factors for equine intestinal parasite infections and reduced efficacy of pyrantel embonate against Parascaris sp.

Gastrointestinal parasites, Parascaris sp. and strongyles, are common in young horses worldwide and control of these parasites is challenged by increasing anthelmintic resistance. Our aim was to identify risk factors for these infections as well as to assess the efficacy of fenbendazole (dose 7.5 mg/kg) and pyrantel embonate (dose 19 mg/kg) against Parascaris sp. We also evaluated association between owner observed symptoms and patent infections with these parasites. Fecal samples were collected from 367 young horses in Finland and a questionnaire study was conducted. Fecal egg counts were performed by Mini-FLOTAC (R) method. Univariable logistic regression models using patent infection status (Yes/No), separately for Parascaris sp. and strongyle infections as an outcome were run initially to screen potential risk factors collected by the questionnaire. After the initial screening, multiple logistic regression models were constructed and run to account for correlated data structure, risk factors and potential confounders simultaneously. Two significant risk factors for a patent Parascaris sp. infection were found: breeding farm size (p = 0.028) and frequency of horse movements (p = 0.010). Horses originating from large breeding farms were more likely (OR = 2.47, 95% confidence interval (CI) 1.10-5.51) to shed Parascaris sp. eggs upon relocation to training stables compared to horses originating from small breeding farms. Horses living in farms with frequent horse movements to other premises had higher odds (OR = 3.56, 95% CI: 1.35-9.39) of a patent Parascaris sp. infection compared to farms with less frequent horse movements. Risk factors for patent strongyle infection included age (p <0.001) and season (p = 0.017). Horses were less likely (OR = 0.27, 95% CI: 0.10-0.66) to shed strongylid eggs during the spring compared to the winter. Horses excreting over 200 ascarid eggs per gram were included in the anthelmintic efficacy trial. A mean FECR less than 90% was interpreted as presence of anthelmintic resistance. The mean FECR was 98.5% (95% CI: 95.8-100) and 68.0% (95% CI: 52.7-83.3) in the fenbendazole (n = 31) and pyrantel (n = 26) treatment groups, respectively. In conclusion, we identified two new risk factors for patent Parascaris sp. infection; breeding farm size and frequency of horse movements. Reduced efficacy of pyrantel against Parascaris sp. was observed for the second time in Europe. A relatively high Parascaris sp. prevalence in yearlings (34%) and two-year-olds (20%) was observed, which has not been reported earlier. An association between symptoms and a patent Parascaris sp. infection was observed in foals.Peer reviewe

Calculus and heat flow in metric measure spaces and applications to spaces with Ricci bounds from below

This paper is devoted to a deeper understanding of the heat flow and to the refinement of calculus tools on metric measure spaces (X,d,m). Our main results are: - A general study of the relations between the Hopf-Lax semigroup and Hamilton-Jacobi equation in metric spaces (X,d). - The equivalence of the heat flow in L^2(X,m) generated by a suitable Dirichlet energy and the Wasserstein gradient flow of the relative entropy functional in the space of probability measures P(X). - The proof of density in energy of Lipschitz functions in the Sobolev space W^{1,2}(X,d,m). - A fine and very general analysis of the differentiability properties of a large class of Kantorovich potentials, in connection with the optimal transport problem. Our results apply in particular to spaces satisfying Ricci curvature bounds in the sense of Lott & Villani [30] and Sturm [39,40], and require neither the doubling property nor the validity of the local Poincar\'e inequality.Comment: Minor typos corrected and many small improvements added. Lemma 2.4, Lemma 2.10, Prop. 5.7, Rem. 5.8, Thm. 6.3 added. Rem. 4.7, Prop. 4.8, Prop. 4.15 and Thm 4.16 augmented/reenforced. Proof of Thm. 4.16 and Lemma 9.6 simplified. Thm. 8.6 corrected. A simpler axiomatization of weak gradients, still equivalent to all other ones, has been propose