Climate change and land cover effects on water yield in a subtropical watershed spanning the yungas-chaco transition of Argentina.

The demand for mountain water resources is increasing, and their availability is threatened by climate change, emphasizing the urgency for effective protection and management. The upper Sali-Dulce watershed holds vital significance as it contributes the majority of the Sali-Dulce water resources, supporting a densely populated dry region in Northwestern Argentina, covering an area of 24,217 km2. However, the potential impact of climate change and land use/land cover change on water yield in this watershed remains uncertain. This study employs the InVEST Annual Water Yield model to analyze the average water yield in the watershed and evaluate its potential changes under future scenarios of climate and land use/land cover change. InVEST was calibrated using data from multiple river gauges located across the watershed, indicating satisfactory performance (R2 = 0.751, p-value = 0.0054). Precipitation and evapotranspiration were the most important variables explaining water yield in the area, followed by land use. Water yield showed a notable concentration in the montane area with 40% of the watershed accounting for 80% of the water yield, underscoring the importance of conserving natural land cover in this critical zone. Climate change scenarios project an increase in water yield ranging from 21 to 75%, while the effects of land cover change scenarios on water yield vary, with reforestation scenarios leading to reductions of up to 15% and expansions in non-irrigated agriculture resulting in increases of up to 40%. Additionally, water yield distribution may become more concentrated or dispersed, largely dependent on the type of land cover. The combined scenarios highlight the pivotal role of land cover in adapting to climate change. Our findings provide valuable insights for designing future studies and developing policies aimed at implementing effective adaptation strategies to climate change within the Salí-Dulce watershed.

Moving from ecological impacts to social vulnerability in data-scarce places.

Managers need to trace social impacts and vulnerability caused by environmental change all the way to its driving forces to target key system components for intervention. However, most available scientific evidence deals with either the ecological impacts of direct drivers or the value of ecosystem benefits to people. Our matrix-based tool combines these types of evidence to make environmental management problems traceable through a structured yet flexible procedure. The tool consists of a series of matrices that sequentially link direct drivers of environmental change, landscapes, ecological conditions, benefits to people, and stakeholder types. Qualitative matrices result from the integration and synthesis of available evidence from literature reviews, and where data is scarce, these are used to elicit quantitative scores from expert opinion. Expert scoring of links and multiplication of matrices allow for estimating the impacts of each driver of environmental change on each stakeholder type and using this information as input to assess stakeholders' vulnerability through impact-influence diagrams. Applying the tool to the Argentine Gran Chaco, a globally threatened ecoregion, yielded a transparent and reliable picture of this data-scarce place, with important management implications. Tracing stakeholder impacts back to direct drivers confirmed that further encroachment of cleared areas around indigenous lands will increase the vulnerability of this social group. Also, assessing confidence levels for every social-ecological link suggested that incentivizing peasant farmers to restore natural forage supply represents a management opportunity to reverse degradation. Our tool makes interdisciplinary frameworks of linked ecological and social systems operational so managers can use the best available knowledge of a place and account for uncertainty to make environmental management decisions.

Global agricultural productivity is threatened by increasing pollinator dependence without a parallel increase in crop diversification.

The global increase in the proportion of land cultivated with pollinator-dependent crops implies increased reliance on pollination services. Yet agricultural practices themselves can profoundly affect pollinator supply and pollination. Extensive monocultures are associated with a limited pollinator supply and reduced pollination, whereas agricultural diversification can enhance both. Therefore, areas where agricultural diversity has increased, or at least been maintained, may better sustain high and more stable productivity of pollinator-dependent crops. Given that >80% of all crops depend, to varying extents, on insect pollination, a global increase in agricultural pollinator dependence over recent decades might have led to a concomitant increase in agricultural diversification. We evaluated whether an increase in the area of pollinator-dependent crops has indeed been associated with an increase in agricultural diversity, measured here as crop diversity, at the global, regional, and country scales for the period 1961-2016. Globally, results show a relatively weak and decelerating rise in agricultural diversity over time that was largely decoupled from the strong and continually increasing trend in agricultural dependency on pollinators. At regional and country levels, there was no consistent relationship between temporal changes in pollinator dependence and crop diversification. Instead, our results show heterogeneous responses in which increasing pollinator dependence for some countries and regions has been associated with either an increase or a decrease in agricultural diversity. Particularly worrisome is a rapid expansion of pollinator-dependent oilseed crops in several countries of the Americas and Asia that has resulted in a decrease in agricultural diversity. In these regions, reliance on pollinators is increasing, yet agricultural practices that undermine pollination services are expanding. Our analysis has thereby identified world regions of particular concern where environmentally damaging practices associated with large-scale, industrial agriculture threaten key ecosystem services that underlie productivity, in addition to other benefits provided by biodiversity.

The health, environmental, and economic dimensions of future dietary transitions in Argentina.

Diets link human health with environmental sustainability, offering promising pressure points to enhance the sustainability of food systems. We investigated the health, environmental, and economic dimensions of the current diet in Argentina and the possible effects of six dietary change scenarios on nutrient adequacy, dietary quality, food expenditure, and six environmental impact categories (i.e., GHG emissions, total land occupation, cropland use, fossil energy use, freshwater consumption, and the emission of eutrophying pollutants). Current dietary patterns are unhealthy, unsustainable, and relatively expensive, and all things being equal, an increase in income levels would not alter the health dimension, but increase environmental impacts by 33-38%, and costs by 38%. Compared to the prevailing diet, the six healthier diet alternatives could improve health with an expenditure between + 27% (National Dietary Guidelines) to -5% (vegan diet) of the current diet. These dietary changes could result in trade-offs between different environmental impacts. Plant-based diets showed the lowest overall environmental impact, with GHG emissions and land occupation reduced by up to 79% and 88%, respectively, without significant changes in cropland demand. However, fossil energy use and freshwater consumption could increase by up to 101% and 220%, respectively. The emission of eutrophying pollutants could increase by up to 54% for all healthy diet scenarios, except for the vegan one (18% decrease). We conclude that the health and environmental crisis that Argentina (and other developing countries) currently face could be mitigated by adopting healthy diets (particularly plant-based), bringing in the process benefits to both people and nature. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11625-021-01087-7.

MCL1 as a Therapeutic Target in Parkinson's Disease?

Dopamine neurons in the substantia nigra (SN) pars compacta are selectively lost during the progression of Parkinson's disease (PD). Recent work performed on the role of the Bcl2 family (highly specialized proteins which control cellular survival and death) in midbrain dopamine neurons has led to the identification of the Bcl2 factor Mcl1 as a weak link in the survival of these neurons. We hypothesize that the regulation of BCL2 proteins may explain this selective vulnerability, and may even provide a novel therapeutic opportunity - strengthening weak links such as MCL1 could result in a delay or complete abrogation of cell death during PD.

Survival of midbrain dopamine neurons depends on the Bcl2 factor Mcl1.

Mitochondria-dependent apoptosis plays an important role in the embryonic development of the midbrain dopaminergic system as well as in Parkinson's disease. Central to mitochondria-dependent apoptosis is the Bcl2 family of apoptosis-regulating proteins. However, it was unclear which Bcl2 proteins are important for the survival of dopaminergic neurons. Here, we identify Mcl1 as a critical Bcl2 pro-survival factor in midbrain dopaminergic neurons. Using a chemical biology approach to inhibit various components of the apoptotic machinery in the dopaminergic MN9D cell line or the control neuroblastoma N2A cell line, we find that functional inhibition of Mcl1 with the high affinity small molecule inhibitor UMI-77 results in a rapid and dose-dependent loss of viability, selectively in dopaminergic cells. In-depth analysis of the apoptotic signaling pathway reveals that chemical inhibition of Mcl1 results in the activation of Bax, activation of cleaved caspase-3 and finally cell death. The dependence of mouse dopaminergic midbrain neurons on Mcl1 was confirmed using ex vivo slice cultures from Pitx3GFP/+ and wildtype mice. In mouse dopaminergic midbrain neurons positive for the midbrain dopaminergic marker Pitx3, or tyrosine hydroxylase, UMI-77 treatment caused a dramatic increase in cleaved caspase 3, indicating that Mcl1 activity is required for basal neuronal survival. Overall, our results suggest that Mcl1 is of critical importance to dopaminergic neurons and is a weak link in the chain controlling cellular survival. Boosting the pro-survival function of Mcl1 should be pursued as a therapeutic approach to augment the resilience of midbrain dopaminergic neurons to apoptotic stress in Parkinson's disease.

Induced Cell Turnover: A Novel Therapeutic Modality for In Situ Tissue Regeneration.

Induced cell turnover (ICT) is a theoretical intervention in which the targeted ablation of damaged, diseased, and/or nonfunctional cells is coupled with replacement by partially differentiated induced pluripotent stem cells in a gradual and multiphasic manner. Tissue-specific ablation can be achieved using pro-apoptotic small molecule cocktails, peptide mimetics, and/or tissue-tropic adeno-associated virus-delivered suicide genes driven by cell type-specific promoters. Replenishment with new cells can be mediated by systemic administration of cells engineered for homing, robustness, and even enhanced function and disease resistance. Otherwise, the controlled release of cells can be achieved using implanted biodegradable scaffolds, hydrogels, and polymer matrixes. In theory, ICT would enable in situ tissue regeneration without the need for surgical transplantation of organs produced ex vivo, and addresses non-transplantable tissues (such as the vasculature, lymph nodes, and the nervous system). This article outlines several complimentary strategies for overcoming barriers to ICT in an effort to stimulate further research at this promising interface of cell therapy, tissue engineering, and regenerative medicine.

RNAi mechanisms in Huntington's disease therapy: siRNA versus shRNA.

Huntington's Disease (HD) is a genetically dominant trinucleotide repeat disorder resulting from CAG repeats within the Huntingtin (HTT) gene exceeding a normal range (> 36 CAGs). Symptoms of the disease manifest in middle age and include chorea, dystonia, and cognitive decline. Typical latency from diagnosis to death is 20 years. There are currently no disease-modifying therapies available to HD patients. RNAi is a potentially curative therapy for HD. A popular line of research employs siRNA or antisense oligonucleotides (ASO) to knock down mutant Huntingtin mRNA (mHTT). Unfortunately, this modality requires repeated dosing, commonly exhibit off target effects (OTEs), and exert renal and hepatic toxicity. In contrast, a single AAV-mediated short-hairpin RNA (shRNA) dose can last years with low toxicity. In addition, we highlight research indicating that shRNA elicits fewer OTEs than siRNA when tested head-to-head. Despite this promise, shRNA therapy has been held back by difficulties controlling expression (oversaturating cells with toxic levels of RNA construct). In this review, we compare RNAi modalities for HD and propose novel methods of optimizing shRNA expression and on-target fidelity.

Neuropharmacological review of the nootropic herb Bacopa monnieri.

This review synthesizes behavioral research with neuromolecular mechanisms putatively involved with the low-toxicity cognitive enhancing action of Bacopa monnieri (BM), a medicinal Ayurvedic herb. BM is traditionally used for various ailments, but is best known as a neural tonic and memory enhancer. Numerous animal and in vitro studies have been conducted, with many evidencing potential medicinal properties. Several randomized, double-blind, placebo-controlled trials have substantiated BM's nootropic utility in humans. There is also evidence for potential attenuation of dementia, Parkinson's disease, and epilepsy. Current evidence suggests BM acts via the following mechanisms-anti-oxidant neuroprotection (via redox and enzyme induction), acetylcholinesterase inhibition and/or choline acetyltransferase activation, ß-amyloid reduction, increased cerebral blood flow, and neurotransmitter modulation (acetylcholine [ACh], 5-hydroxytryptamine [5-HT], dopamine [DA]). BM appears to exhibit low toxicity in model organisms and humans; however, long-term studies of toxicity in humans have yet to be conducted. This review will integrate molecular neuroscience with behavioral research.

Colecistectomía laparoscópica sin clips / Laparoscopic cholecystectomy without clips

Antecedentes: el uso del "clip" simplificó las maniobras de hemostasia y bilistasia durante la colecistectomía laparascópica (CL), pero incorporó una nueva morbilidad a ésta intervención. Objetivo: comparar la CL hecha de la forma más difundida, con la que apela a reemplazar el "clip" por un punto en el cístico y por hemostasia bipolar en la arteria cística. Lugar de aplicación: Unidad de Cirugía Ambulatoria, Fundación "Carlos Oulton", Córdoba. Diseño: estudio prospectivo de comparación de 2 series. Población: 179 mujeres y 71 hombres, operados entre el 04-12-98 y 06-09-2000, 90 con "clips" y 89 sin "clips". Métodos: en cada serie se recogió, de manera prospectiva, la siguiente información: duración de la intervención, tiempo de internación, analgesia postoperatoria y morbilidad vinculada a la técnica utilizada. Resultados: la duración de la intervención fue 6' promedio más larga en la serie sin "clips". En 11 casos de ésta serie el cirujano apeló a un "clip" y en 3 a un "endoloop" para asegurar la bilistasia. La hemostasia bipolar de la arteria cística no necesitó "clips" en ningún caso. La duración de la internación, lo mismo que el consumo de analgésicos, fue idéntica en ambas series. Hubo una reinternación por biloma en la serie de CL sin "clips". Conclusiones: el "clip" metálico simplifica los gestos de cierre del cístico durante la CL, pero se le atribuye responsabilidad en el incremento de bilomas y bilirragias postoperatorias, ya que la bilistasia que ofrece es menos segura que la provista por un punto o una ligadura. La asociación de hemostasia monopolar y "clips" metálicos es potencialmente letal para la vía biliar principal. La hemostasia de la arteria cística con coagulación bipolar es una técnica segura. Se propone reemplazar el "clip" por un punto o una ligadura en el cístico y por hemostasia bipolar en la arteria, con el objetivo de hacer más segura la intervención