Pandemics of the 21st Century: The Risk Factor for Obese People.
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ABSTRACT:
SUBMITTER: Hanckova M
PROVIDER: S-EPMC8779521 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:There is no good science in bad models. Cell culture is especially prone to artifacts. A number of novel cell culture technologies have become more broadly available in the 21st century, which allow overcoming limitations of traditional culture and are more physiologically relevant. These include the use of stem-cell derived human cells, cocultures of different cell types, scaffolds and extracellular matrices, perfusion platforms (such as microfluidics), 3D culture, organ-on-chip technologies, tissue architecture, and organ functionality. The physiological relevance of such models is further enhanced by the measurement of biomarkers (e.g., key events of pathways), organ specific functionality, and more comprehensive assessment cell responses by high-content methods. These approaches are still rarely combined to create microphysiological systems. The complexity of the combination of these technologies can generate results closer to the in vivo situation but increases the number of parameters to control, bringing some new challenges. In fact, we do not argue that all cell culture needs to be that sophisticated. The efforts taken are determined by the purpose of our experiments and tests. If only a very specific molecular target to cell response is of interest, a very simple model, which reflects this, might be much more suited to allow standardization and high-throughput. However, the less defined the end point of interest and cellular response are, the better we should approximate organ- or tissue-like culture conditions to make physiological responses more probable. Besides these technologic advances, important progress in the quality assurance and reporting on cell cultures as well as the validation of cellular test systems brings the utility of cell cultures to a new level. The advancement and broader implementation of Good Cell Culture Practice (GCCP) is key here. In toxicology, this is a major prerequisite for meaningful and reliable results, ultimately supporting risk assessment and product development decisions.
| S-EPMC5578455 | biostudies-literature
Project description:BackgroundSome carcinogenic viruses are known to be transmissible by blood transfusion. Intensive viral screening of transfused blood now exists in most countries. In the UK, high-sensitivity nucleic acid amplification tests for hepatitis C virus were introduced in 1999 and it was thought that this would reduce, and possibly eliminate, transfusion-related liver cancer. We aimed to investigate cancer risk in recipients of blood transfusion in 2000 or after.MethodsA total of 1.3 million UK women recruited in 1998 on average were followed for hospital records of blood transfusion and for cancer registrations. After excluding women with cancer or precancerous conditions before or at the time of transfusion, Cox regression yielded adjusted relative risks of 11 site-specific cancers for women with compared to without prior blood transfusion.ResultsDuring follow up, 11 274 (0.9%) women had a first recorded transfusion in 2000 or after, and 1648 (14.6%) of them were subsequently diagnosed with cancer, a mean 6.8 years after the transfusion. In the first 5 years after transfusion there were significant excesses for most site-specific cancers examined, presumably because some had preclinical cancer. However, 5 or more years (mean 8 years) after blood transfusion, there were significant excess risks only for liver cancer (adjusted relative risk = 2.63, 95%CI 1.45-4.78) and for non-Hodgkin lymphoma (adjusted relative risk = 1.74, 1.21-2.51). When analyses were restricted to those undergoing hip or knee replacement surgery, the commonest procedure associated with transfusion, these relative risks were not materially altered.ConclusionsIn a large cohort of UK women, transfusions in the 21st century were associated with long-term increased risks of liver cancer and non-Hodgkin lymphoma. Some of these malignancies may have been caused by carcinogenic agents that are not currently screened for in transfused blood.
| S-EPMC5391695 | biostudies-literature
Project description:It has been nearly 50 years since the golden age of antibiotic discovery (1945-1975) ended; yet, we still struggle to identify novel drug targets and to deliver new chemical classes of antibiotics to replace those rendered obsolete by drug resistance. Despite herculean efforts utilizing a wide range of antibiotic discovery platform strategies, including genomics, bioinformatics, systems biology and postgenomic approaches, success has been at best incremental. Obviously, finding new classes of antibiotics is really hard, so repeating the old strategies, while expecting different outcomes, seems to boarder on insanity. The key questions dealt with in this review include: (1) If mutation based drug resistance is the major challenge to any new antibiotic, is it possible to find drug targets and new chemical entities that can escape this outcome; (2) Is the number of novel chemical classes of antibacterials limited by the number of broad spectrum drug targets; and (3) If true, then should we focus efforts on subgroups of pathogens like Gram negative or positive bacteria only, anaerobic bacteria or other group where the range of common essential genes is likely greater?. This review also provides some examples of existing drug targets that appear to escape the specter of mutation based drug resistance, and provides examples of some intermediate spectrum strategies as well as modern molecular and genomic approaches likely to improve the odds of delivering 21st century medicines to combat multidrug resistant pathogens.
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Project description: Not available
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Project description:In the Southwest and Central Plains of Western North America, climate change is expected to increase drought severity in the coming decades. These regions nevertheless experienced extended Medieval-era droughts that were more persistent than any historical event, providing crucial targets in the paleoclimate record for benchmarking the severity of future drought risks. We use an empirical drought reconstruction and three soil moisture metrics from 17 state-of-the-art general circulation models to show that these models project significantly drier conditions in the later half of the 21st century compared to the 20th century and earlier paleoclimatic intervals. This desiccation is consistent across most of the models and moisture balance variables, indicating a coherent and robust drying response to warming despite the diversity of models and metrics analyzed. Notably, future drought risk will likely exceed even the driest centuries of the Medieval Climate Anomaly (1100-1300 CE) in both moderate (RCP 4.5) and high (RCP 8.5) future emissions scenarios, leading to unprecedented drought conditions during the last millennium.
| S-EPMC4644081 | biostudies-other
Project description:Haldane's Rule (HR), which states that 'when in the offspring of two different animal races one sex is absent, rare, or sterile, that sex is the heterozygous (heterogametic) sex', is one of the most general patterns in speciation biology. We review the literature of the past 15 years and find that among the ?85 new studies, many consider taxa that traditionally have not been the focus for HR investigations. The new studies increased to nine, the number of 'phylogenetically independent' groups that comply with HR. They continue to support the dominance and faster-male theories as explanations for HR, although due to increased reliance on indirect data (from, for example, differential introgression of cytoplasmic versus chromosomal loci in natural hybrid zones) unambiguous novel results are rare. We further highlight how research on organisms with sex determination systems different from those traditionally considered may lead to more insight in the underlying causes of HR. In particular, haplodiploid organisms provide opportunities for testing specific predictions of the dominance and faster X chromosome theory, and we present new data that show that the faster-male component of HR is supported in hermaphrodites, suggesting that genes involved in male function may evolve faster than those expressed in the female function.
| S-EPMC3178397 | biostudies-literature
Project description: Not available
| S-EPMC3539946 | biostudies-literature
Project description:We propose an integrated model of aqueous outflow control that employs a pump-conduit system in this article. Our model exploits accepted physiologic regulatory mechanisms such as those of the arterial, venous, and lymphatic systems. Here, we also provide a framework for developing novel diagnostic and therapeutic strategies to improve glaucoma patient care. In the model, the trabecular meshwork distends and recoils in response to continuous physiologic IOP transients like the ocular pulse, blinking, and eye movement. The elasticity of the trabecular meshwork determines cyclic volume changes in Schlemm's canal (SC). Tube-like SC inlet valves provide aqueous entry into the canal, and outlet valve leaflets at collector channels control aqueous exit from SC. Connections between the pressure-sensing trabecular meshwork and the outlet valve leaflets dynamically control flow from SC. Normal function requires regulation of the trabecular meshwork properties that determine distention and recoil. The aqueous pump-conduit provides short-term pressure control by varying stroke volume in response to pressure changes. Modulating TM constituents that regulate stroke volume provides long-term control. The aqueous outflow pump fails in glaucoma due to the loss of trabecular tissue elastance, as well as alterations in ciliary body tension. These processes lead to SC wall apposition and loss of motion. Visible evidence of pump failure includes a lack of pulsatile aqueous discharge into aqueous veins and reduced ability to reflux blood into SC. These alterations in the functional properties are challenging to monitor clinically. Phase-sensitive OCT now permits noninvasive, quantitative measurement of pulse-dependent TM motion in humans. This proposed conceptual model and related techniques offer a novel framework for understanding mechanisms, improving management, and development of therapeutic options for glaucoma.
| S-EPMC8126645 | biostudies-literature
Project description:Policies that attempt to curb greenhouse gas emissions, allocate emissions rights, or distribute compensation to those most damaged by climate change must explicitly incorporate the international heterogeneity of the climate change threat. To capture the distinct susceptibilities associated with lack of infrastructure, potential property loss, and gross human exposure, we develop an integration of climate change projections and poverty, wealth, and population metrics. Our analysis shows that most nations of the world are threatened by the interaction of regional climatic changes with one or more relevant socioeconomic factors. Nations that have the highest levels of poverty, wealth, and population face greater relative exposure in those dimensions. However, for each of those socioeconomic indicators, spatial heterogeneity in projected climate change determines the overall international pattern of socioclimatic exposure. Our synthesis provides a critical missing piece to the climate change debate and should facilitate the formulation of climate policies that account for international variations in the threat of climate change across a range of socioeconomic dimensions.
| S-EPMC2154407 | biostudies-literature
Project description:Serotonin (5-hydroxytryptamine [5-HT]) is accumulated within nerve endings by the serotonin transporter (SERT), which terminates its extracellular action and provides cytoplasmic 5-HT for refilling of synaptic vesicles. SERT is the target for many antidepressant medications as well as psychostimulants such as cocaine and ecstasy (3,4-methylenedioxymethamphetamine). SERT belongs to the SLC6 family of ion-coupled transporters and is structurally related to several other transporter families. SERT was studied in the 1970s and 1980s using membrane vesicles isolated from blood platelets. These studies led to a proposed stoichiometry of transport that has been challenged by high-resolution structures of SERT and its homologues and by studies of SERT electrophysiology. Here, we review the original evidence alongside more recent structural and electrophysiological evidence. A self-consistent picture emerges with surprising insights into the ion fluxes that accompany 5-HT transport.
| S-EPMC6829555 | biostudies-literature