Developmental Sex Differences in the Metabolism of Cardiolipin in Mouse Cerebral Cortex Mitochondria

Cardiolipin (CL) is a mitochondrial-specific phospholipid. CL content and acyl chain composition are crucial for energy production. Given that estradiol induces CL synthesis in neurons, we aimed to assess CL metabolism in the cerebral cortex (CC) of male and female mice during early postnatal life, when sex steroids induce sex-dimorphic maturation of the brain. Despite the fact that total amount of CL was similar, its fatty acid composition differed between males and females at birth. In males, CL was more mature (lower saturation ratio) and the expression of the enzymes involved in synthetic and remodeling pathways was higher, compared to females. Importantly, the sex differences found in CL metabolism were due to the testosterone peak that male mice experience perinatally. These changes were associated with a higher expression of UCP-2 and its activators in the CC of males. Overall, our results suggest that the perinatal testosterone surge in male mice regulates CL biosynthesis and remodeling in the CC, inducing a sex-dimorphic fatty acid composition. In male's CC, CL is more susceptible to peroxidation, likely explaining the testosterone-dependent induction of neuroprotective molecules such as UCP-2. These differences may account for the sex-dependent mitochondrial susceptibility after perinatal hypoxia/ischemia.Instituto de Investigaciones Bioquímicas de La Plat

Developmental Sex Differences in the Metabolism of Cardiolipin in Mouse Cerebral Cortex Mitochondria

Cardiolipin (CL) is a mitochondrial-specific phospholipid. CL content and acyl chain composition are crucial for energy production. Given that estradiol induces CL synthesis in neurons, we aimed to assess CL metabolism in the cerebral cortex (CC) of male and female mice during early postnatal life, when sex steroids induce sex-dimorphic maturation of the brain. Despite the fact that total amount of CL was similar, its fatty acid composition differed between males and females at birth. In males, CL was more mature (lower saturation ratio) and the expression of the enzymes involved in synthetic and remodeling pathways was higher, compared to females. Importantly, the sex differences found in CL metabolism were due to the testosterone peak that male mice experience perinatally. These changes were associated with a higher expression of UCP-2 and its activators in the CC of males. Overall, our results suggest that the perinatal testosterone surge in male mice regulates CL biosynthesis and remodeling in the CC, inducing a sex-dimorphic fatty acid composition. In male's CC, CL is more susceptible to peroxidation, likely explaining the testosterone-dependent induction of neuroprotective molecules such as UCP-2. These differences may account for the sex-dependent mitochondrial susceptibility after perinatal hypoxia/ischemia.Instituto de Investigaciones Bioquímicas de La Plat

No Forest Left Behind

Mitigating climate change by reducing deforestation should involve incentives for countries that currently have high forest cover and low deforestation rates

Developmental Sex Differences in the Metabolism of Cardiolipin in Mouse Cerebral Cortex Mitochondria

Cardiolipin (CL) is a mitochondrial-specific phospholipid. CL content and acyl chain composition are crucial for energy production. Given that estradiol induces CL synthesis in neurons, we aimed to assess CL metabolism in the cerebral cortex (CC) of male and female mice during early postnatal life, when sex steroids induce sex-dimorphic maturation of the brain. Despite the fact that total amount of CL was similar, its fatty acid composition differed between males and females at birth. In males, CL was more mature (lower saturation ratio) and the expression of the enzymes involved in synthetic and remodeling pathways was higher, compared to females. Importantly, the sex differences found in CL metabolism were due to the testosterone peak that male mice experience perinatally. These changes were associated with a higher expression of UCP-2 and its activators in the CC of males. Overall, our results suggest that the perinatal testosterone surge in male mice regulates CL biosynthesis and remodeling in the CC, inducing a sex-dimorphic fatty acid composition. In male's CC, CL is more susceptible to peroxidation, likely explaining the testosterone-dependent induction of neuroprotective molecules such as UCP-2. These differences may account for the sex-dependent mitochondrial susceptibility after perinatal hypoxia/ischemia.Instituto de Investigaciones Bioquímicas de La Plat

Economic Aspects of Sanitation in Developing Countries

Improved sanitation has been shown to have great impacts on people's health and economy. However, the progress of achieving the Millennium Development Goals (MDGs) on halving the proportion of people without access to clean water and basic sanitation by 2015 has thus far been delayed. One of the reasons for the slow progress is that policy makers, as well as the general public, have not fully understood the importance of the improved sanitation solutions. This paper, by gathering relevant research findings, aims to report and discuss currently available evidence on the economic aspects of sanitation, including the economic impacts of unimproved sanitation and the costs and economic benefits of some common improved sanitation options in developing countries.; DATA USED IN THIS PAPER WERE OBTAINED FROM DIFFERENT INFORMATION SOURCES: international and national journal articles and reports, web-based statistics, and fact sheets. We used both online search and hand search methods to gather the information.; Scientific evidence has demonstrated that the economic cost associated with poor sanitation is substantial. At the global level, failure to meet the MDG water and sanitation target would have ramifications in the area of US$38 billion, and sanitation accounts for 92$142 billion (US$year 2005). This translates to a per capita spending of US$28 for sanitation. Annually, this translates to roughly US$14 million. The evidence complied in this paper demonstrates that investing in sanitation is socially and economically worthwhile. For every US$1 invested, achieving the sanitation MDG target and universal sanitation access in the non-OECD countries would result in a global return of US$9.1 and US$11.2, respectively.; Given the current state of knowledge, sanitation is undeniably a profitable investment. It is clear that achieving the MDG sanitation target not only saves lives but also provides a foundation for economic growth

A snapshot of cancer-associated thromboembolic disease in 2018-2019: First data from the TESEO prospective registry

BACKGROUND: The ever-growing complexity of cancer-associated thrombosis (CAT), with new antineoplastic drugs and anticoagulants, distinctive characteristics, and decisions with low levels of evidence, justifies this registry. METHOD: TESEO is a prospective registry promoted by the Spanish Society of Medical Oncology to which 34 centers contribute cases. It seeks to provide an epidemiological description of CAT in Spain. RESULTS: Participants (N=939) with CAT diagnosed between July 2018 and December 2019 were recruited. Most subjects had advanced colon (21.4%), non-small cell lung (19.2%), and breast (11.1%) cancers, treated with dual-agent chemotherapy (28.4%), monochemotherapy (14.4%), or immune checkpoint inhibitors (3.6%). Half (51%) were unsuspected events, albeit only 57.1% were truly asymptomatic. Pulmonary embolism (PE) was recorded in 571 (58.3%); in 120/571 (21.0%), there was a concurrent deep venous thromboembolism (VTE). Most initially received low molecular weight heparin (89.7%). Suspected and unsuspected VTE had an OS rate of 9.9 (95% CI, 7.3-non-computable) and 14.4 months (95% CI, 12.6-non-computable) (p=0.00038). Six-month survival was 80.9%, 55.9%, and 55.5% for unsuspected PE, unsuspected PE admitted for another reason, and suspected PE, respectively (p<0.0001). The 12-month cumulative incidence of venous rethrombosis was 7.1% (95% CI, 4.7-10.2) in stage IV vs 3.0% (95% CI, 0.9-7.1) in stages I-III. The 12-month cumulative incidence of major/clinically relevant bleeding was 9.6% (95% CI, 6.1-14.0) in the presence of risk factors. CONCLUSION: CAT continues to be a relevant problem in the era of immunotherapy and targeted therapies. The initial TESEO data highlight the evolution of CAT, with new agents and thrombotic risk factors

Limits to dark matter annihilation cross-section from a combined analysis of MAGIC and Fermi-LAT observations of dwarf satellite galaxies

We present the first joint analysis of gamma-ray data from the MAGIC Cherenkov telescopes and the Fermi Large Area Telescope (LAT) to search for gamma-ray signals from dark matter annihilation in dwarf satellite galaxies. We combine 158 hours of Segue 1 observations with MAGIC with 6-year observations of 15 dwarf satellite galaxies by the Fermi-LAT. We obtain limits on the annihilation cross-section for dark matter particle masses between 10 GeV and 100 TeV - the widest mass range ever explored by a single gamma-ray analysis. These limits improve on previously published Fermi-LAT and MAGIC results by up to a factor of two at certain masses. Our new inclusive analysis approach is completely generic and can be used to perform a global, sensitivity-optimized dark matter search by combining data from present and future gamma-ray and neutrino detectors.Comment: 19 pages, 3 figures. V2: Few typos corrected and references added. Matches published version JCAP 02 (2016) 03

Long-term multi-wavelength variability and correlation study of Markarian 421 from 2007 to 2009

We study the multi-band variability and correlations of the TeV blazar Mrk 421 on year time scales, which can bring additional insight on the processes responsible for its broadband emission. We observed Mrk 421 in the very high energy (VHE) gamma-ray range with the Cherenkov telescope MAGIC-I from March 2007 to June 2009 for a total of 96 hours of effective time after quality cuts. The VHE flux variability is quantified with several methods, including the Bayesian Block algorithm, which is applied to data from Cherenkov telescopes for the first time. The 2.3 year long MAGIC light curve is complemented with data from the Swift/BAT and RXTE/ASM satellites and the KVA, GASP-WEBT, OVRO, and Mets\"ahovi telescopes from February 2007 to July 2009, allowing for an excellent characterisation of the multi-band variability and correlations over year time scales. Mrk 421 was found in different gamma-ray emission states during the 2.3 year long observation period. Flares and different levels of variability in the gamma-ray light curve could be identified with the Bayesian Block algorithm. The same behaviour of a quiet and active emission was found in the X-ray light curves measured by Swift/BAT and the RXTE/ASM, with a direct correlation in time. The behaviour of the optical light curve of GASP-WEBT and the radio light curves by OVRO and Mets\"ahovi are different as they show no coincident features with the higher energetic light curves and a less variable emission. The fractional variability is overall increasing with energy. The comparable variability in the X-ray and VHE bands and their direct correlation during both high- and low-activity periods spanning many months show that the electron populations radiating the X-ray and gamma-ray photons are either the same, as expected in the Synchrotron-Self-Compton mechanism, or at least strongly correlated, as expected in electromagnetic cascades.Comment: Corresponding authors: Ann-Kristin Overkemping ([email protected]), Marina Manganaro ([email protected]), Diego Tescaro ([email protected]), To be published in Astronomy&Astrophysics (A&A), 12 pages, 9 figure