Immunomodulatory Potential of <em>Lactobacillus acidophilus</em>: Implications in Bone Health

Lactobacillus acidophilus is homofermentative anaerobic rod-shaped gram-positive bacteria. L. acidophilous is one of the most common probiotics and is used for the treatment of various gastrointestinal, metabolic and inflammatory disorders. L. acidophilous produces antimicrobial compounds, maintains gut permeability and prevents dysbiosis. L. acidophilus also shows various other properties such as: it is anticarcinogenic, lowers serum cholesterol level and improves lactase metabolism of host. One of the most significant property of L. acidophilous is that it modulates the immune system and can prevent various inflammatory disorders. L. acidophilous influences several immune cells such as Th17 cells and Tregs. Various studies reported that inflammation induces bone loss and leads to several bone pathologies such as osteoporosis, rheumatoid arthritis and periodontitis. Recent studies have shown the potential of probiotics in preventing inflammation mediated bone loss. L. acidophilous is one of these probiotics and is found capable in inhibition of various bone disorders. L. acidophilous restores the dysregulated immune homeostasis and prevents inflammatory bone loss. Thus, L. acidophilous can be a potential therapeutic for the management of various bone pathologies. In this book chapter we reviewed various immunomodulatory properties of L. acidophilous along with its efficacy in preventing dysbiosis and maintaining gut permeability. We also discussed the potential role of L. acidophilous as a therapeutic for the management of inflammation induced bone disorders

Theoretical Studies on the Isomers of Quinazolinone by first Principles

Abstract The present communication is aimed at comparing the molecular structural properties, vibrational and energetic data of 2-and 4-quinazolinone, the two isomers of Quinazolinone, a biologically active hetrocyclic compound, in gas phase, due to their pharmacological activities and applications. The ground state properties of the two isomers have been calculated employing DFT/ B3LYP level of theory using the basis sets 6-311G(d), 6-311+G(d,p), 6-311++G(d,p). The dipole moment and mean polarizability are calculated to be 6.4687 Debye and 110.202/a.

Climate change: the necessary, the possible and the desirable Earth League climate statement on the implications for climate policy from the 5th IPCC Assessment

The development of human civilisations has occurred at a time of stable climate. This climate stability is now threatened by human activity. The rising global climate risk occurs at a decisive moment for world development. World nations are currently discussing a global development agenda consequent to the Millennium Development Goals (MDGs), which ends in 2015. It is increasingly possible to envisage a world where absolute poverty is largely eradicated within one generation and where ambitious goals on universal access and equal opportunities for dignified lives are adopted. These grand aspirations for a world population approaching or even exceeding nine billion in 2050 is threatened by substantial global environmental risks and by rising inequality. Research shows that development gains, in both rich and poor nations, can be undermined by social, economic and ecological problems caused by human-induced global environmental change. Climate risks, and associated changes in marine and terrestrial ecosystems that regulate the resilience of the climate system, are at the forefront of these global risks. We, as citizens with a strong engagement in Earth system science and socio-ecological dynamics, share the vision of a more equitable and prosperous future for the world, yet we also see threats to this future from shifts in climate and environmental processes. Without collaborative action now, our shared Earth system may not be able to sustainably support a large proportion of humanity in the decades ahead

Ten new insights in climate science 2020 – a horizon scan

Non-technical summary We summarize some of the past year's most important findings within climate change-related research. New research has improved our understanding of Earth's sensitivity to carbon dioxide, finds that permafrost thaw could release more carbon emissions than expected and that the uptake of carbon in tropical ecosystems is weakening. Adverse impacts on human society include increasing water shortages and impacts on mental health. Options for solutions emerge from rethinking economic models, rights-based litigation, strengthened governance systems and a new social contract. The disruption caused by COVID-19 could be seized as an opportunity for positive change, directing economic stimulus towards sustainable investments. Technical summary A synthesis is made of ten fields within climate science where there have been significant advances since mid-2019, through an expert elicitation process with broad disciplinary scope. Findings include: (1) a better understanding of equilibrium climate sensitivity; (2) abrupt thaw as an accelerator of carbon release from permafrost; (3) changes to global and regional land carbon sinks; (4) impacts of climate change on water crises, including equity perspectives; (5) adverse effects on mental health from climate change; (6) immediate effects on climate of the COVID-19 pandemic and requirements for recovery packages to deliver on the Paris Agreement; (7) suggested long-term changes to governance and a social contract to address climate change, learning from the current pandemic, (8) updated positive cost–benefit ratio and new perspectives on the potential for green growth in the short- and long-term perspective; (9) urban electrification as a strategy to move towards low-carbon energy systems and (10) rights-based litigation as an increasingly important method to address climate change, with recent clarifications on the legal standing and representation of future generations. Social media summary Stronger permafrost thaw, COVID-19 effects and growing mental health impacts among highlights of latest climate science

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

Regulatory Design for Disaster Preparedness and Recovery by Infrastructure Providers: South Asian Experience

Abstract Infrastructure development using private investment is being pursued in many developing countries at present. Inadequate attention paid to disaster preparedness and recovery in regulatory frameworks and practices can have serious negative effects on investment, and thereby on infrastructure development. Of course, this is in addition to the immediate damage to consumers. India has been a leader in energy-sector liberalization. The super-cyclone that devastated parts of Orissa state within months of privatization of the electricity distribution system highlighted problems of regulatory responses to massive destruction of infrastructure. The Orissa experience yields valuable lessons on regulatory design (e.g., allocation of restoration costs and insurance) as well as post-disaster responses. Sri Lanka, which began telecommunication reforms in 1991, included conditions related to disaster preparedness and recovery in almost all the licenses issued to operators. However, a 1998-99 pilot study on emergency telecommunications found that all parties, including the regulator, had ignored them and that there was little readiness for a disaster or a recovery therefrom. The pilot study, though not fully implemented, contains useful insights on the regulatory aspects of disaster preparedness and recovery. The paper identifies elements of regulatory design for disaster preparedness and effective recovery, while ensuring the safeguarding of conditions conducive to private investment