Despite the abundance of bacterial species in soil, more than 99% of these species cannot be cultured by traditional techniques. In addition, the less than 1% of bacteria that can be cultured are not ...representative of the total phylogenetic diversity. Hence, identifying novel species and their new functions is still an important task for all microbiologists. Cultivating techniques have played an important role in identifying new species but are still low-throughput processes. This review discusses the issues surrounding cultivation, including achievements, limitations, challenges, and future directions.
Skeletal muscle fibers differentiate into specific fiber types with distinct metabolic properties determined by their reliance on oxidative phosphorylation (OXPHOS). Using in vivo approaches, we find ...that OXPHOS-dependent fibers, compared to glycolytic fibers, contain elongated mitochondrial networks with higher fusion rates that are dependent on the mitofusins Mfn1 and Mfn2. Switching of a glycolytic fiber to an oxidative IIA type is associated with elongation of mitochondria, suggesting that mitochondrial fusion is linked to metabolic state. Furthermore, we reveal that mitochondrial proteins are compartmentalized to discrete domains centered around their nuclei of origin. The domain dimensions are dependent on fiber type and are regulated by the mitochondrial dynamics proteins Mfn1, Mfn2, and Mff. Our results indicate that mitochondrial dynamics is tailored to fiber type physiology and provides a rationale for the segmental defects characteristic of aged and diseased muscle fibers.
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•Oxidative muscle fibers have elevated rates of mitochondrial fusion•Mitochondrial fusion responds to the metabolic state of the myofiber•Mitochondrial proteins are compartmentalized into discrete domains•The length of mitochondrial domains is dependent on fusion and fission
Using a combination of elegant approaches, Mishra et al. show that mitochondrial dynamics is tailored to the specific metabolic state of different types of skeletal muscle fibers. They also show that mitochondrial proteins are compartmentalized to discrete domains, which has implications for mitochondrial and aging-related disorders.
Update on massive transfusion Pham, H.P.; Shaz, B.H.
British journal of anaesthesia : BJA,
12/2013, Letnik:
111, Številka:
suppl_1
Journal Article
Recenzirano
Odprti dostop
Massive haemorrhage requires massive transfusion (MT) to maintain adequate circulation and haemostasis. For optimal management of massively bleeding patients, regardless of aetiology (trauma, ...obstetrical, surgical), effective preparation and communication between transfusion and other laboratory services and clinical teams are essential. A well-defined MT protocol is a valuable tool to delineate how blood products are ordered, prepared, and delivered; determine laboratory algorithms to use as transfusion guidelines; and outline duties and facilitate communication between involved personnel. In MT patients, it is crucial to practice damage control resuscitation and to administer blood products early in the resuscitation. Trauma patients are often admitted with early trauma-induced coagulopathy (ETIC), which is associated with mortality; the aetiology of ETIC is likely multifactorial. Current data support that trauma patients treated with higher ratios of plasma and platelet to red blood cell transfusions have improved outcomes, but further clinical investigation is needed. Additionally, tranexamic acid has been shown to decrease the mortality in trauma patients requiring MT. Greater use of cryoprecipitate or fibrinogen concentrate might be beneficial in MT patients from obstetrical causes. The risks and benefits for other therapies (prothrombin complex concentrate, recombinant activated factor VII, or whole blood) are not clearly defined in MT patients. Throughout the resuscitation, the patient should be closely monitored and both metabolic and coagulation abnormalities corrected. Further studies are needed to clarify the optimal ratios of blood products, treatment based on underlying clinical disorder, use of alternative therapies, and integration of laboratory testing results in the management of massively bleeding patients.
The new era of nanotechnology has produced advanced nanomaterials applicable to various fields of medicine, including diagnostic bio-imaging, chemotherapy, targeted drug delivery, and biosensors. ...Various materials are formed into nanoparticles, such as gold nanomaterials, carbon quantum dots, and liposomes. The nanomaterials have been functionalized and widely used because they are biocompatible and easy to design and prepare. This review mainly focuses on nanomaterials responsive to the external stimuli used in drug-delivery systems. To overcome the drawbacks of conventional therapeutics to a tumor, the dual- and multi-responsive behaviors of nanoparticles have been harnessed to improve efficiency from a drug delivery point of view. Issues and future research related to these nanomaterial-based stimuli sensitivities and the scope of stimuli-responsive systems for nanomedicine applications are discussed.
Many major river deltas in the world are subsiding and consequently become increasingly vulnerable to flooding and storm surges, salinization and permanent inundation. For the Mekong Delta, annual ...subsidence rates up to several centimetres have been reported. Excessive groundwater extraction is suggested as the main driver. As groundwater levels drop, subsidence is induced through aquifer compaction. Over the past 25 years, groundwater exploitation has increased dramatically, transforming the delta from an almost undisturbed hydrogeological state to a situation with increasing aquifer depletion. Yet the exact contribution of groundwater exploitation to subsidence in the Mekong delta has remained unknown. In this study we deployed a delta-wide modelling approach, comprising a 3D hydrogeological model with an integrated subsidence module. This provides a quantitative spatially-explicit assessment of groundwater extraction-induced subsidence for the entire Mekong delta since the start of widespread overexploitation of the groundwater reserves. We find that subsidence related to groundwater extraction has gradually increased in the past decades with highest sinking rates at present. During the past 25 years, the delta sank on average ∼18 cm as a consequence of groundwater withdrawal. Current average subsidence rates due to groundwater extraction in our best estimate model amount to 1.1 cm yr−1, with areas subsiding over 2.5 cm yr−1, outpacing global sea level rise almost by an order of magnitude. Given the increasing trends in groundwater demand in the delta, the current rates are likely to increase in the near future.
Patients who have esophageal eosinophilia without gastroesophageal reflux disease (GERD) nevertheless can respond to proton pump inhibitors (PPIs), which can have anti-inflammatory actions ...independent of effects on gastric acid secretion. In esophageal cell cultures, omeprazole has been reported to inhibit Th2 cytokine-stimulated expression of eotaxin-3, an eosinophil chemoattractant contributing to esophageal eosinophilia in eosinophilic esophagitis (EoE). The objective of this study was to elucidate molecular mechanisms underlying PPI inhibition of IL-4-stimulated eotaxin-3 production by esophageal cells.
Telomerase-immortalized and primary cultures of esophageal squamous cells from EoE patients were treated with IL-4 in the presence or absence of acid-activated omeprazole or lansoprazole. We measured eotaxin-3 protein secretion by ELISA, mRNA expression by PCR, STAT6 phosphorylation and nuclear translocation by Western blotting, eotaxin-3 promoter activation by an exogenous reporter construct, and STAT6, RNA polymerase II, and trimethylated H3K4 binding to the endogenous eotaxin-3 promoter by ChIP assay. Omeprazole in concentrations ≥5 µM significantly decreased IL-4-stimulated eotaxin-3 protein secretion and mRNA expression. Lansoprazole also blocked eotaxin-3 protein secretion. Omeprazole had no effect on eotaxin-3 mRNA stability or on STAT6 phosphorylation and STAT6 nuclear translocation. Rather, omeprazole blocked binding of IL-4-stimulated STAT6, RNA polymerase II, and trimethylated H3K4 to the eotaxin-3 promoter.
PPIs, in concentrations achieved in blood with conventional dosing, significantly inhibit IL-4-stimulated eotaxin-3 expression in EoE esophageal cells and block STAT6 binding to the promoter. These findings elucidate molecular mechanisms whereby patients with Th2 cytokine-driven esophageal eosinophilia can respond to PPIs, independent of effects on gastric acid secretion.
The Pioneer Accountable Care Organization (ACO) Model aims to drive health care organizations to reduce expenditures while improving quality for fee-for-service (FFS) Medicare beneficiaries.
To ...determine whether FFS beneficiaries aligned with Pioneer ACOs had smaller increases in spending and utilization than other FFS beneficiaries while retaining similar levels of care satisfaction in the first 2 years of the Pioneer ACO Model.
Participants were FFS Medicare beneficiaries aligned with 32 ACOs (n = 675,712 in 2012; n = 806,258 in 2013) and a comparison group of alignment-eligible beneficiaries in the same markets (n = 13,203,694 in 2012; n = 12,134,154 in 2013). Analyses comprised difference-in-differences multivariable regression with Oaxaca-Blinder reweighting to model expenditure and utilization outcomes over a 2-year performance period (2012-2013) and 2-year baseline period (2010-2011) as well as adjusted analyses of Consumer Assessment of Healthcare Providers & Systems (CAHPS) survey responses among random samples of beneficiaries in Pioneer ACOs (n = 13,097), FFS (n = 116,255), or Medicare Advantage (n = 203,736) for 2012 care.
Beneficiary alignment with a Pioneer ACO in 2012 or 2013.
Medicare spending, utilization, and CAHPS domain scores.
Total spending for beneficiaries aligned with Pioneer ACOs in 2012 or 2013 increased from baseline to a lesser degree relative to comparison populations. Differential changes in spending were approximately -$35.62 (95% CI, -$40.12 to -$31.12) per-beneficiary-per-month (PBPM) in 2012 and -$11.18 (95% CI, -$15.84 to -$6.51) PBPM in 2013, which amounted to aggregate reductions in increases of approximately -$280 (95% CI, -$315 to -$244) million in 2012 and -$105 (95% CI, -$148 to -$61) million in 2013. Inpatient spending showed the largest differential change of any spending category (-$14.40 95% CI, -$17.31 to -$11.49 PBPM in 2012; -$6.46 95% CI, -$9.26 to -$3.66 PBPM in 2013). Changes in utilization of physician services, emergency department, and postacute care followed a similar pattern. Compared with other Medicare beneficiaries, ACO-aligned beneficiaries reported higher mean scores for timely care (77.2 ACO vs 71.2 FFS vs 72.7 MA) and for clinician communication (91.9 ACO vs 88.3 FFS vs 88.7 MA).
In the first 2 years of the Pioneer ACO Model, beneficiaries aligned with Pioneer ACOs, as compared with general Medicare FFS beneficiaries, exhibited smaller increases in total Medicare expenditures and differential reductions in utilization of different health services, with little difference in patient experience.
The signal transducer and activator of transcription 5 (STAT5) regulates differentiation, survival, proliferation and transformation of hematopoietic cells. Upon cytokine stimulation, STAT5 tyrosine ...phosphorylation (pYSTAT5) is transient, while in diverse neoplastic cells persistent overexpression and enhanced pYSTAT5 are frequently found. Post-translational modifications might contribute to enhanced STAT5 activation in the context of transformation, but the strength and duration of pYSTAT5 are incompletely understood. We found that O-GlcNAcylation and tyrosine phosphorylation act together to trigger pYSTAT5 levels and oncogenic transcription in neoplastic cells. The expression of a mutated hyperactive gain-of-function (GOF) STAT5 without O-GlcNAcylation resulted in decreased tyrosine phosphorylation, oligomerization and transactivation potential and complete loss of oncogenic transformation capacity. The lack of O-GlcNAcylation diminished phospho-ERK and phospho-AKT levels. Our data show that O-GlcNAcylation of STAT5 is an important process that contributes to oncogenic transcription through enhanced STAT5 tyrosine phosphorylation and oligomerization driving myeloid transformation. O-GlcNAcylation of STAT5 could be required for nutrient sensing and metabolism of cancer cells.
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