Understanding the effect of oxidative and ER stress on CHO cell culture and product quality through multivariate analysis

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Biomass stocks in Ghanaian cocoa ecosystems: the effects of region, management and stand age of cocoa trees

Determination of biomass produced in cocoa ecosystems is an important step towards quantifying the carbon sequestration potential of cocoa production systems. This study provides data on the biomass of cocoa systems being influenced by management, cocoa stand ages and region. Eight cocoa farms were sampled on the basis of three variables: region (Eastern, Western region), shade management (shaded, unshaded) and stand age (15 years). Allometric equations (R2 > 0.94) were developed to estimate the biomass of live cocoa trees, while the biomass of non-cocoa trees was estimated using an existing equation by FAO. Generally, biomass stocks were higher in the Eastern than Western region, shaded than unshaded, and in stands >15 years than those <15 years. The total cocoa ecosystem biomass range was, 48.1 ± 6.5 to 101.6 ± 12.6 Mg/ha. The high biomass estimates reveals a potential of system to restore appreciable biomass losses resulting from deforestation and forest degradation in Ghana

Leaf Litter Decomposition and Mitigation of CO₂ Emissions in Cocoa Ecosystems

Studies simultaneously quantifying litter weight losses and rates of CO2-C evolved are few, though essential for accurate estimates of forest carbon budgets. A 120-day dry matter loss and a 130-day carbon emission experiments were concurrently conducted at the soil laboratory of the University of Reading, UK. Leaf litters of tree species comprising cocoa (Theobroma cacao), Newbouldia laevis (dominant shade tree in Eastern region (ER)) and Persea americana (dominant shade tree in Western region (WR)) of Ghana were incubated using a single tree leaf litter and/or a 1:1 mixed species leaf litters to determine and predict the litter decomposition and C dynamics in cocoa systems with or without the shade trees. Decomposition and C release trends in the ER systems followed: shade > mixed cocoa-shade = predicted mixed litter > cocoa; and in the WR, the order was: cocoa = mixed cocoa-shade > predicted mixed > shade. Differences between released C estimated from litter weight loss and CO2-C evolution measurement methods were not consistent. Regression analysis revealed a strong (R2 = 0.71) relationship between loss of litter C and the CO2-C evolution during litter decomposition. The large C pool for shaded cocoa systems indicates the potential to store more C and thus, its promotion could play a significant role in atmospheric CO2 mitigations

Rag GTPases and phosphatidylinositol 3-phosphate mediate recruitment of the AP-5/SPG11/SPG15 complex.

Adaptor protein complex 5 (AP-5) and its partners, SPG11 and SPG15, are recruited onto late endosomes and lysosomes. Here we show that recruitment of AP-5/SPG11/SPG15 is enhanced in starved cells and occurs by coincidence detection, requiring both phosphatidylinositol 3-phosphate (PI3P) and Rag GTPases. PI3P binding is via the SPG15 FYVE domain, which, on its own, localizes to early endosomes. GDP-locked RagC promotes recruitment of AP-5/SPG11/SPG15, while GTP-locked RagA prevents its recruitment. Our results uncover an interplay between AP-5/SPG11/SPG15 and the mTORC1 pathway and help to explain the phenotype of AP-5/SPG11/SPG15 deficiency in patients, including the defect in autophagic lysosome reformation

Controllability analysis to identify manipulated variables for a glycosylation control strategy

N-linked glycans affect important end-use characteristics such as the bioactivity and efficacy of many therapeutic proteins, (including monoclonal antibodies), in vivo. However, achieving a precise glycan distribution during manufacturing can be challenging because glycosylation is a non-template driven cellular process, with the potential for significant uncontrolled variability in glycan distributions. As important as the glycan distribution is to the end-use performance of biopharmaceuticals, to date, no strategy exists for controlling glycosylation on-line. In this work, we present a controllability analysis for glycosylation as a first step toward establishing an online glycosylation control strategy. We first assessed the theoretically achievable extent to which the very complex process of glycosylation is controllable. Once theoretic controllability was established, we performed experiments to identify appropriate manipulated variables that can be used to direct the glycan distribution of an IgG1 to a desired state. We found that bioreactor process variables such as glucose and glutamine media concentration, temperature, pH, agitation rate, and dissolved oxygen (DO) had significant but small effects on the relative percentage of various glycans. This indicated that the IgG1 glycan distribution was generally robust to even large perturbations of typical bioreactor variables. Conversely, we found that media supplementation with manganese, galactose, and ammonia had significant and large effects on certain glycans. From this work, we determined that manganese can be used as a manipulated variable to increase the relative abundance of M5 and decrease FA2 glycans simultaneously, and galactose can be used as a manipulated variable to increase the relative abundance of FA2G1 and decrease FA2 and A2 simultaneously. As a final test, we applied machine learning algorithms to validate and enrich these findings from a data-centric point of view. The machine learning algorithms provided an avenue to discover unknown relationships and patterns that refined our findings and provided a framework to explore more variables

High Mass Triple Systems: The Classical Cepheid Y Car

We have obtained an HST STIS ultraviolet high dispersion Echelle mode spectrum the binary companion of the double mode classical Cepheid Y Car. The velocity measured for the hot companion from this spectrum is very different from reasonable predictions for binary motion, implying that the companion is itself a short period binary. The measured velocity changed by 7 km/ s during the 4 days between two segments of the observation confirming this interpretation. We summarize "binary" Cepheids which are in fact members of triple system and find at least 44% are triples. The summary of information on Cepheids with orbits makes it likely that the fraction is under-estimated.Comment: accepted by A

Statin use and adverse effects among adults \u3e 75 years of age: Insights from the Patient and Provider Assessment of Lipid Management (PALM) registry

Background: Current statin use and symptoms among older adults in routine community practice have not been well characterized since the release of the 2013 American College of Cardiology/American Heart Association guideline. Methods and results: We compared statin use and dosing between adults \u3e75 and ≤75 years old who were eligible for primary or secondary prevention statin use without considering guideline-recommended age criteria. The patients were treated at 138 US practices in the Patient and Provider Assessment of Lipid Management (PALM) registry in 2015. Patient surveys also evaluated reported symptoms while taking statins. Multivariable logistic regression models examined the association between older age and statin use and dosing. Among 6717 people enrolled, 1704 (25%) were \u3e75 years old. For primary prevention, use of any statin or high-dose statin did not vary by age group: any statin, 62.6% in those \u3e75 years old versus 63.1% in those ≤75 years old (P=0.83); high-dose statin, 10.2% versus 12.3% in the same groups (P=0.14). For secondary prevention, older patients were slightly less likely to receive any statin (80.1% versus 84.2% [P=0.003]; adjusted odds ratio, 0.81; 95% confidence interval, 0.66-1.01 [P=0.06]), but were much less likely to receive a high-intensity statin (23.5% versus 36.2% [PP=0.0001]). Among current statin users, older patients were slightly less likely to report any symptoms (41.3% versus 46.6%; P=0.003) or myalgias (27.3% versus 33.3%; Conclusions: Overall use of statins was similar for primary prevention in those aged \u3e75 years versus younger patients, yet older patients were less likely to receive high-intensity statins for secondary prevention. Statins appear to be similarly tolerated in older and younger adult

Patient-reported reasons for declining or discontinuing statin therapy: Insights from the PALM registry

Background: Many adults eligible for statin therapy for cardiovascular disease prevention are untreated. Our objective was to investigate patient‐reported reasons for statin underutilization, including noninitiation, refusal, and discontinuation.Methods and Results: This study included the 5693 adults recommended for statin therapy in the PALM (Patient and Provider Assessment of Lipid Management) registry. Patient surveys evaluated statin experience, reasons for declining or discontinuing statins, and beliefs about statins and cardiovascular disease risk. Overall, 1511 of 5693 adults (26.5%) were not on treatment. Of those not on a statin, 894 (59.2%) reported never being offered a statin, 153 (10.1%) declined a statin, and 464 (30.7%) had discontinued therapy. Women (relative risk: 1.22), black adults (relative risk: 1.48), and those without insurance (relative risk: 1.38) were most likely to report never being offered a statin. Fear of side effects and perceived side effects were the most common reasons cited for declining or discontinuing a statin. Compared with statin users, those who declined or discontinued statins were less likely to believe statins are safe (70.4% of current users vs. 36.9% of those who declined and 37.4% of those who discontinued) or effective (86.3%, 67.4%, and 69.1%, respectively). Willingness to take a statin was high; 67.7% of those never offered and 59.7% of patients who discontinued a statin would consider initiating or retrying a statin.Conclusions: More than half of patients eligible for statin therapy but not on treatment reported never being offered one by their doctor. Concern about side effects was the leading reason for statin refusal or discontinuation. Many patients were willing to reconsider statin therapy if offered

Measurement of low‐density lipoprotein cholesterol levels in primary and secondary prevention patients: Insights from the PALM registry

Background The 2013 American College of Cardiology/American Heart Association Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults recommended testing low-density lipoprotein cholesterol ( LDL -C) to identify untreated patients with LDL -C ≥190 mg/dL, assess lipid-lowering therapy adherence, and consider nonstatin therapy. We sought to determine whether clinician lipid testing practices were consistent with these guidelines. Methods and Results The PALM (Patient and Provider Assessment of Lipid Management) registry enrolled primary and secondary prevention patients from 140 US cardiology, endocrinology, and primary care offices in 2015 and captured demographic data, lipid treatment history, and the highest LDL -C level in the past 2 years. Core laboratory lipid levels were drawn at enrollment. Among 7627 patients, 2787 (36.5%) had no LDL -C levels measured in the 2 years before enrollment. Patients without chart-documented LDL -C levels were more often women, nonwhite, uninsured, and non-college graduates (all P\u3c0.01). Patients without prior lipid testing were less likely to receive statin treatment (72.6% versus 76.0%; P=0.0034), a high-intensity statin (21.5% versus 24.3%; P=0.016), nonstatin lipid-lowering therapy (24.8% versus 27.3%; P=0.037), and had higher core laboratory LDL -C levels at enrollment (median 97 versus 92 mg/dL; P\u3c0.0001) than patients with prior LDL -C testing. Of 166 individuals with core laboratory LDL -C levels ≥190 mg/dL, 36.1% had no LDL -C measurement in the prior 2 years, and 57.2% were not on a statin at the time of enrollment. Conclusions In routine clinical practice, LDL -C testing is associated with higher-intensity lipid-lowering treatment and lower achieved LDL -C level