Cutaneous neurofibromas Current clinical and pathologic issues

ObjectiveTo present the current terminology and natural history of neurofibromatosis 1 (NF1) cutaneous neurofibromas (cNF).MethodsNF1 experts from various research and clinical backgrounds reviewed the terms currently in use for cNF as well as the clinical, histologic, and radiographic features of these tumors using published and unpublished data.ResultsNeurofibromas develop within nerves, soft tissue, and skin. The primary distinction between cNF and other neurofibromas is that cNF are limited to the skin whereas other neurofibromas may involve the skin, but are not limited to the skin. There are important cellular, molecular, histologic, and clinical features of cNF. Each of these factors is discussed in consideration of a clinicopathologic framework for cNF.ConclusionThe development of effective therapies for cNF requires formulation of diagnostic criteria that encompass the clinical and histologic features of these tumors. However, there are several areas of overlap between cNF and other neurofibromas that make distinctions between cutaneous and other neurofibromas more difficult, requiring careful deliberation with input across the multiple disciplines that encounter these tumors and ultimately, prospective validation. The ultimate goal of this work is to facilitate accurate diagnosis and meaningful therapeutics for cNF

The International Natural Product Sciences Taskforce (INPST) and the power of Twitter networking exemplified through #INPST hashtag analysis

Background: The development of digital technologies and the evolution of open innovation approaches have enabled the creation of diverse virtual organizations and enterprises coordinating their activities primarily online. The open innovation platform titled "International Natural Product Sciences Taskforce" (INPST) was established in 2018, to bring together in collaborative environment individuals and organizations interested in natural product scientific research, and to empower their interactions by using digital communication tools. Methods: In this work, we present a general overview of INPST activities and showcase the specific use of Twitter as a powerful networking tool that was used to host a one-week "2021 INPST Twitter Networking Event" (spanning from 31st May 2021 to 6th June 2021) based on the application of the Twitter hashtag #INPST. Results and Conclusion: The use of this hashtag during the networking event period was analyzed with Symplur Signals (https://www.symplur.com/), revealing a total of 6,036 tweets, shared by 686 users, which generated a total of 65,004,773 impressions (views of the respective tweets). This networking event's achieved high visibility and participation rate showcases a convincing example of how this social media platform can be used as a highly effective tool to host virtual Twitter-based international biomedical research events

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

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Not AvailableMonitoring of heavy metals was conducted in the Yamuna River considering bioaccumulation factor, exposure concentration, and human health implications which showed contamination levels of copper (Cu), lead (Pb), nickel (Ni), and chromium (Cr) and their dispersion patterns along the river. Largest concentration of Pb in river water was 392 μg L−1; Cu was 392 μg L−1 at the extreme downstream, Allahabad and Ni was 146 μg L−1 at midstream, Agra. Largest concentration of Cu was 617 μg kg−1, Ni 1,621 μg kg−1 at midstream while Pb was 1,214 μg kg−1 at Allahabad in surface sediment. The bioconcentration of Cu, Pb, Ni, and Cr was observed where the largest accumulation of Pb was 2.29 μg kg−1 in Oreochromis niloticus and 1.55 μg kg−1 in Cyprinus carpio invaded at Allahabad while largest concentration of Ni was 174 μg kg−1 in O. niloticus and 124 μg kg−1 in C. carpio in the midstream of the river. The calculated values of hazard index (HI) for Pb was found more than one which indicated human health concern. Carcinogenic risk value for Ni was again high i.e., 17.02×10−4 which was larger than all other metals studied. The results of this study indicated bioconcentration in fish due to their exposures to heavy metals from different routes which had human health risk implications. Thus, regular environmental monitoring of heavy metal contamination in fish is advocated for assessing food safety since health risk may be associated with the consumption of fish contaminatedNot Availabl

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Not AvailableInvasion, spread and predominance of alien invasive fishes were studied in 950-km-long stretch of the Yamuna River. The fish yield ranged between 32 t/km/yr to 240 t/km/yr and the catch of alien invasive fishes dominated over local fishes in the fishery, which was over 96% at Etawah. The calculated Invasion Coefficient Index (Ixi) of alien invasive fishes was in the range of 0.12 to 0.31 indicating a major loss to the local fish diversity. The calculated Pearson’s correlation coefficient was found to have positive correlation of 0.757 and 0.710 for common carp and tilapia respectively with locally captured Indian major carps (IMC). The results of this study highlighted how unintentional spread of alien invasive fishes due to rapid aquaculture diversification and intensification has invaded into the Yamuna River causing severe loss to the local fishery. The invasion of alien fishes has been mapped for the Yamuna River at different locations using GIS tools. The results of this study invite attention on the management and sustainability of the local fishery and ecosystem health of the river.Not Availabl

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Not AvailableInvasion, spread and predominance of alien invasive fishes were studied in 950-km-long stretch of the Yamuna River. The fish yield ranged between 32 t/km/yr to 240 t/km/yr and the catch of alien invasive fishes dominated over local fishes in the fishery, which was over 96% at Etawah. The calculated Invasion Coefficient Index (Ixi) of alien invasive fishes was in the range of 0.12 to 0.31 indicating a major loss to the local fish diversity. The calculated Pearson’s correlation coefficient was found to have positive correlation of 0.757 and 0.710 for common carp and tilapia respectively with locally captured Indian major carps (IMC). The results of this study highlighted how unintentional spread of alien invasive fishes due to rapid aquaculture diversification and intensification has invaded into the Yamuna River causing severe loss to the local fishery. The invasion of alien fishes has been mapped for the Yamuna River at different locations using GIS tools. The results of this study invite attention on the management and sustainability of the local fishery and ecosystem health of the river.Biodiversity Board, Lucknow ,Uttar Pradesh State

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Not AvailableInvasion, spread and predominance of alien invasive fishes were studied in 950-km-long stretch of the Yamuna River. The fish yield ranged between 32 t/km/yr to 240 t/km/yr and the catch of alien invasive fishes dominated over local fishes in the fishery, which was over 96% at Etawah. The calculated Invasion Coefficient Index (Ixi) of alien invasive fishes was in the range of 0.12 to 0.31 indicating a major loss to the local fish diversity. The calculated Pearson’s correlation coefficient was found to have positive correlation of 0.757 and 0.710 for common carp and tilapia respectively with locally captured Indian major carps (IMC). The results of this study highlighted how unintentional spread of alien invasive fishes due to rapid aquaculture diversification and intensification has invaded into the Yamuna River causing severe loss to the local fishery. The invasion of alien fishes has been mapped for the Yamuna River at different locations using GIS tools. The results of this study invite attention on the management and sustainability of the local fishery and ecosystem health of the river.Not Availabl

A steady-state modeling approach to validate an in vivo mechanism of the GAL regulatory network in Saccharomyces cerevisiae

Cellular regulation is a result of complex interactions arising from DNA–protein and protein–protein binding, autoregulation, and compartmentalization and shuttling of regulatory proteins. Experiments in molecular biology have identified these mechanisms recruited by a regulatory network. Mathematical models may be used to complement the knowledge-base provided by in vitro experimental methods. Interactions identified by in vitro experiments can lead to the hypothesis of multiple candidate models explaining the in vivo mechanism. The equilibrium dissociation constants for the various interactions and the total component concentration constitute constraints on the candidate models. In this work, we identify the most plausible in vivo network by comparing the output response to the experimental data. We demonstrate the methodology using the GAL system of Saccharomyces cerevisiae for which the steady-state analysis reveals that Gal3p neither dimerizes nor shuttles between the cytoplasm and the nucleus