Mesenchymal stem cell-based therapy for ischemic stroke

Ischemic stroke represents a major, worldwide health burden with increasing incidence. Patients affected by ischemic strokes currently have few clinically approved treatment options available. Most currently approved treatments for ischemic stroke have narrow therapeutic windows, severely limiting the number of patients able to be treated. Mesenchymal stem cells represent a promising novel treatment for ischemic stroke. Numerous studies have demonstrated that mesenchymal stem cells functionally improve outcomes in rodent models of ischemic stroke. Recent studies have also shown that exosomes secreted by mesenchymal stem cells mediate much of this effect. In the present review, we summarize the current literature on the use of mesenchymal stem cells to treat ischemic stroke. Further studies investigating the mechanisms underlying mesenchymal stem cells tissue healing effects are warranted and would be of benefit to the field

External sources of clean technology: evidence from the clean development mechanism

New technology is fundamental to sustainable development. However, inventors from industrialized countries often refuse technology transfer because they worry about reverse-engineering. When can clean technology transfer succeed? We develop a formal model of the political economy of North–South technology transfer. According to the model, technology transfer is possible if (1) the technology in focus has limited global commercial potential or (2) the host developing country does not have the capacity to absorb new technologies for commercial use. If both conditions fail, inventors from industrialized countries worry about the adverse competitiveness effects of reverse-engineering, so technology transfer fails. Data analysis of technology transfer in 4,894 projects implemented under the Kyoto Protocol’s Clean Development Mechanism during the 2004–2010 period provides evidence in support of the model

Climate as a risk factor for armed conflict

This is the author accepted manuscriptResearch findings on the relationship between climate and conflict are diverse and contested. Here we assess the current understanding of the relationship between climate and conflict, based on the structured judgments of experts from diverse disciplines. These experts agree that climate has affected organized armed conflict within countries. However, other drivers, such as low socioeconomic development and low capabilities of the state, are judged to be substantially more influential, and the mechanisms of climate–conflict linkages remain a key uncertainty. Intensifying climate change is estimated to increase future risks of conflict.European Research Counci

Rectal Transmission of Transmitted/Founder HIV-1 Is Efficiently Prevented by Topical 1% Tenofovir in BLT Humanized Mice

Rectal microbicides are being developed to prevent new HIV infections in both men and women. We focused our in vivo preclinical efficacy study on rectally-applied tenofovir. BLT humanized mice (n = 43) were rectally inoculated with either the primary isolate HIV-1(JRCSF) or the MSM-derived transmitted/founder (T/F) virus HIV-1(THRO) within 30 minutes following treatment with topical 1% tenofovir or vehicle. Under our experimental conditions, in the absence of drug treatment we observed 50% and 60% rectal transmission by HIV-1(JRCSF) and HIV-1(THRO), respectively. Topical tenofovir reduced rectal transmission to 8% (1/12; log rank p = 0.03) for HIV-1(JRCSF) and 0% (0/6; log rank p = 0.02) for HIV-1(THRO). This is the first demonstration that any human T/F HIV-1 rectally infects humanized mice and that transmission of the T/F virus can be efficiently blocked by rectally applied 1% tenofovir. These results obtained in BLT mice, along with recent ex vivo, Phase 1 trial and non-human primate reports, provide a critically important step forward in the development of tenofovir-based rectal microbicides

Biophysical and electrochemical studies of protein-nucleic acid interactions

This review is devoted to biophysical and electrochemical methods used for studying protein-nucleic acid (NA) interactions. The importance of NA structure and protein-NA recognition for essential cellular processes, such as replication or transcription, is discussed to provide background for description of a range of biophysical chemistry methods that are applied to study a wide scope of protein-DNA and protein-RNA complexes. These techniques employ different detection principles with specific advantages and limitations and are often combined as mutually complementary approaches to provide a complete description of the interactions. Electrochemical methods have proven to be of great utility in such studies because they provide sensitive measurements and can be combined with other approaches that facilitate the protein-NA interactions. Recent applications of electrochemical methods in studies of protein-NA interactions are discussed in detail

Human Rights Shaming Through INGOs and Foreign Aid Delivery

Does the ``shaming" of human rights violations influence foreign aid delivery decisions across OECD donor countries? We examine the effect of shaming, defined as targeted negative attention by human rights international nongovernmental organizations (INGOs), on donor decisions about how to deliver bilateral aid. We argue that INGO shaming of recipient countries leads donor governments, on average, to ``bypass" the recipient government in favor of non-state aid delivery channels, including international and local NGOs and international organizations (IOs). However, we expect this relationship to be conditional on a donor country's position in the international system. Minor power countries have limited influence in global affairs and are therefore more able to centrally promote human rights in their foreign policy. Major power countries, on the other hand, shape world politics and often confront ``realpolitik" concerns that may require government-to-government aid relations in the presence of INGO shaming. We expect aid officials of minor donor countries to be more likely to condition aid delivery decisions on human rights shaming than their counterparts of major donor countries. Using compositional data analysis, we test our argument using originally collected data on human rights shaming events in a time-series cross-sectional framework from 2004 to 2010. We find support for our hypotheses: On average, OECD donor governments increase the proportion of bypass when INGOs shame the recipient government. When differentiating between donor types we find that this finding holds for minor but not for major powers. These results add to both our understanding of the influences of aid allocation decision-making and our understanding of the role of INGOs on foreign-policy

A phase 1 randomized, open label, rectal safety, acceptability, pharmacokinetic, and pharmacodynamic study of three formulations of tenofovir 1% Gel (the CHARM-01 study)

Objectives: The CHARM-01 study characterized the safety, acceptability, pharmacokinetics (PK), and pharmacodynamics (PD) of three tenofovir (TFV) gels for rectal application. The vaginal formulation (VF) gel was previously used in the CAPRISA 004 and VOICE vaginal microbicide Phase 2B trials and the RMP-02/MTN-006 Phase 1 rectal safety study. The reduced glycerin VF (RGVF) gel was used in the MTN-007 Phase 1 rectal microbicide trial and is currently being evaluated in the MTN-017 Phase 2 rectal microbicide trial. A third rectal specific formulation (RF) gel was also evaluated in the CHARM-01 study. Methods: Participants received 4 mL of the three TFV gels in a blinded, crossover design: seven daily doses of RGVF, seven daily doses of RF, and six daily doses of placebo followed by one dose of VF, in a randomized sequence. Safety, acceptability, compartmental PK, and explant PD were monitored throughout the trial. Results: All three gels were found to be safe and acceptable. RF and RGVF PK were not significantly different. Median mucosal mononuclear cell (MMC) TFV-DP trended toward higher values for RF compared to RGVF (1136 and 320 fmol/106 cells respectively). Use of each gel in vivo was associated with significant inhibition of ex vivo colorectal tissue HIV infection. There was also a significant negative correlation between the tissue levels of TFV, tissue TFV-DP, MMC TFV-DP, rectal fluid TFV, and explant HIV-1 infection. Conclusions: All three formulations were found to be safe and acceptable. However, the safety profile of the VF gel was only based on exposure to one dose whereas participants received seven doses of the RGVF and RF gels. There was a trend towards higher tissue MMC levels of TFV-DP associated with use of the RF gel. Use of all gels was associated with significant inhibition of ex vivo tissue HIV infection. Trial Registration: ClinicalTrials.gov NCT01575405

Benchmarking scientific performance by decomposing leadership of Cuban and Latin American institutions in Public Health

This is a post-peer-review, pre-copyedit version of an article published in Scientometrics. The final authenticated version is available online at: http://dx.doi.org/10.1007/s11192-015-1831-z”.Comparative benchmarking with bibliometric indicators can be an aid in decision-making with regard to research management. This study aims to characterize scientific performance in a domain (Public Health) by the institutions of a country (Cuba), taking as reference world output and regional output (other Latin American centers) during the period 2003–2012. A new approach is used here to assess to what extent the leadership of a specific institution can change its citation impact. Cuba was found to have a high level of specialization and scientific leadership that does not match the low international visibility of Cuban institutions. This leading output appears mainly in non-collaborative papers, in national journals; publication in English is very scarce and the rate of international collaboration is very low. The Instituto de Medicina Tropical Pedro Kouri stands out, alone, as a national reference. Meanwhile, at the regional level, Latin American institutions deserving mention for their high autonomy in normalized citation would include Universidad de Buenos Aires (ARG), Universidade Federal de Pelotas (BRA), Consejo Nacional de Investigaciones Cientı´ficas y Te´cnicas (ARG), Instituto Oswaldo Cruz (BRA) and the Centro de Pesquisas Rene Rachou (BRA). We identify a crucial aspect that can give rise to misinterpretations of data: a high share of leadership cannot be considered positive for institutions when it is mainly associated with a high proportion of non-collaborative papers and a very low level of performance. Because leadership might be questionable in some cases, we propose future studies to ensure a better interpretation of findings.This work was made possible through financing by the scholarship funds for international mobility between Andalusian and IberoAmerican Universities and the SCImago GroupPeer reviewe

Comparative genomics of Cluster O mycobacteriophages

Mycobacteriophages - viruses of mycobacterial hosts - are genetically diverse but morphologically are all classified in the Caudovirales with double-stranded DNA and tails. We describe here a group of five closely related mycobacteriophages - Corndog, Catdawg, Dylan, Firecracker, and YungJamal - designated as Cluster O with long flexible tails but with unusual prolate capsids. Proteomic analysis of phage Corndog particles, Catdawg particles, and Corndog-infected cells confirms expression of half of the predicted gene products and indicates a non-canonical mechanism for translation of the Corndog tape measure protein. Bioinformatic analysis identifies 8-9 strongly predicted SigA promoters and all five Cluster O genomes contain more than 30 copies of a 17 bp repeat sequence with dyad symmetry located throughout the genomes. Comparison of the Cluster O phages provides insights into phage genome evolution including the processes of gene flux by horizontal genetic exchange