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Purpose: Localized shimming in single‐voxel MRS often results in large B0 inhomogeneity outside the volume‐of‐interest. This causes unacceptable degradation in motion navigator images. Switching back and forth between whole‐brain shim and localized shim is possible for linear shims, but not for higher‐order shims. Here we propose motion navigators largely insensitive to B0 inhomogeneity for prospective motion‐corrected MRS with localized higher‐order shimming. Methods: A recent fast high‐resolution motion navigator based on spiral‐in/out k‐space trajectories and multislice‐to‐volume registration was modified by splitting the readout into multiple shot interleaves which shortened the echo time and reduced the effect of B0 inhomogeneity. The performance of motion correction was assessed in healthy subjects in the prefrontal cortex using a sLASER sequence at 3T (N = 5) and 7T (N = 5). Results: With multiple spatial interleaves, excellent quality navigator images were acquired in the whole brain in spite of large B0 inhomogeneity outside the MRS voxel. The total duration of the navigator in sLASER remained relatively short even with multiple shots (3T: 10 spatial interleaves 94 ms per slice; 7T: 15 spatial interleaves 103 ms per slice). Prospective motion correction using the multi‐shot navigators yielded comparable spectral quality (water linewidth and metabolite SNR) with and without subject motion. Conclusion: B0‐insensitive motion navigators enable prospective motion correction for MRS with all first‐ and second‐order shims adjusted in the MRS voxel, providing optimal spectral linewidth. [ABSTRACT FROM AUTHOR]

The reaction of Re(CO)5Br with deprotonated 1H‐(5‐(2,2′:6′,2′′‐terpyridine)pyrid‐2‐yl)tetrazole yields a triangular assembly formed by tricarbonyl Re(I) vertices. Photophysical measurements reveal blue‐green emission with a maximum at 520 nm, 32 % quantum yield, and 2430 ns long‐lived excited state decay lifetime in deaerated dichloromethane solution. Coordination of lanthanoid ions to the terpyridine units red‐shifts the emission to 570 nm and also reveals efficient (90 %) and fast sensitisation of both Eu(III) and Yb(III) at room temperature, with a similar rate constant kET on the order of 107 s−1. Efficient sensitisation of Eu(III) from Re(I) is unprecedented, especially when considering the close proximity in energy between the donor and acceptor excited states. On the other hand, comparative measurements at 77 K reveal that energy transfer to Yb(III) is two orders of magnitude slower than that to Eu(III). A two‐step mechanism of sensitisation is therefore proposed, whereby the rate‐determining step is a thermally activated energy transfer step between the Re(I) centre and the terpyridine functionality, followed by rapid energy transfer to the respective Ln(III) excited states. At 77 K, the direct Re(I) to Eu(III) energy transfer seems to proceed via a ligand‐mediated superexchange Dexter‐type mechanism. [ABSTRACT FROM AUTHOR]

Shade trees in agroforestry systems confer ecosystem services, such as enhanced soil fertility from diverse litter inputs, microclimate regulation via shade, and disease mitigation through trophic and abiotic interactions. With this thriving role of agroforestry in sustainable agriculture, particularly for tree crops, systematic and reliable methods to select shade trees for specific agroecosystem outcomes are crucial.Plant functional traits offer a framework to describe, select and manage shade trees. Over the last decade, shade tree leaf functional traits and whole plant traits have been assessed in agroforestry systems. Yet, we lack amalgamated information on (i) what we know about shade tree trait relationships with functions to achieve desired agroecosystem outcomes, (ii) how decades of shade tree selection by farmers impacts agroforests inter‐ and intraspecific trait diversity, and (iii) which shade tree traits should be considered for achieving farmer priorities.We consolidate literature on Coffea arabica (coffee) and Theobroma cacao (cocoa) agroforestry systems to summarize the role of shade tree functional traits in three key ecosystem functions: soil fertility, microclimate modification and crop productivity. We compile global and regional datasets on tree functional trait diversity to show the functional space of agroforestry tree species compared with the overall functional space observed in plants.Despite, or maybe because of, high shade tree diversity, shade tree trait characterization remains coarse and commonly measured at the community scale in the literature. Based on published trait data, we show that farmers adjust the functional composition of shade trees to increase the recycling of soil nutrients (high leaf nitrogen), the production of wood (skewing towards lower wood densities) and the production of fruits (tendency towards high seed size). Common shade trees in coffee and cocoa systems fall in the mid‐range of leaf acquisitive to conservative strategies, providing evidence that expanding shade tree portfolios can improve, or even accelerate, functions.Synthesis and applications: Based on the agroforestry literature and on trait‐environment relationships, we propose a matrix of shade tree traits that influence desirable agroecosystem outcomes for farmers, which can guide fine‐scale coordination of trait expression and agroforestry functions. [ABSTRACT FROM AUTHOR]

Purpose: To develop a fast high‐resolution image‐based motion correction method using spiral navigators with multislice‐to‐volume registration. Methods: A semi‐LASER sequence was modified to include a multislice spiral navigator for prospective motion correction (∼305 ms including acquisition, processing, and feedback) as well as shim and frequency navigators for prospective shim and frequency correction (∼100 ms for each). MR spectra were obtained in the prefrontal cortex in five healthy subjects at 3 T with and without prospective motion and shim correction. The effect of key navigator parameters (number of slices, image resolution, and excitation flip angle) on registration accuracy was assessed using simulations. Results: Without prospective motion and shim correction, spectral quality degraded significantly in the presence of voluntary motion. In contrast, with prospective motion and shim correction, spectral quality was improved (metabolite linewidth = 6.7 ± 0.6 Hz, SNR= 67 ± 9) and in good agreement with baseline data without motion (metabolite linewidth = 6.9 ± 0.9 Hz, SNR = 73 ± 9). In addition, there was no significant difference in metabolites concentrations measured without motion and with prospective motion and shim correction in the presence of motion. Simulations showed that the registration precision was comparable when using three navigator slices with 3 mm resolution and when using the entire volume (all slices) with 8 mm resolution. Conclusion: The proposed motion correction scheme allows fast and precise prospective motion and shim correction for single‐voxel spectroscopy at 3 T. With 3 mm resolution, only a few navigator slices are necessary to achieve excellent motion correction performance. [ABSTRACT FROM AUTHOR]

Singlet fission (SF) is a potential avenue for augmenting the performance of silicon photovoltaics, but the scarcity of SF materials energy‐matched to silicon represents a barrier to the commercial realization of this technology. In this work, a molecular engineering approach is described to increase the energy of the S1 and T1 energy levels of diketopyrrolopyrrole derivatives such that the energy‐level requirements for exothermic SF and energy‐transfer to silicon are met. Time‐resolved photoluminescence studies show that the silicon‐matched materials are SF active in the solid state, forming a correlated triplet pair 1(TT) – a crucial intermediate in the SF process – as observed through Herzberg‐Teller emission from 1(TT) at both 77 K and room temperature. Transient electron paramagnetic resonance studies show that the correlated triplet pair does not readily separate into the unbound triplets, which is a requirement for energy harvesting by silicon. The fact that the triplet pair do not separate into free triplets is attributed to the intermolecular crystal packing within the thin films. Nevertheless, these results demonstrate a promising route for energy‐tuning silicon‐matched SF materials. [ABSTRACT FROM AUTHOR]

Purpose: To develop prospective motion correction for single‐voxel MRS in the human cervical spinal cord. Methods: A motion MR navigator was implemented using reduced field‐of‐view 2D‐selective RF excitation together with EPI readout. A short‐echo semi‐LASER sequence (TE = 30 ms) was updated to incorporate this real‐time image‐based motion navigator, as well as real‐time shim and frequency navigators. Five healthy participants were studied at 3 T with a 64‐channel head–neck receive coil. Single‐voxel MRS data were measured in a voxel located at the C3‐5 vertebrae level. The motion navigator was used to correct for translations in the X‐Y plane and was validated by assessing spectral quality with and without prospective correction in the presence of subject motion. Results: Without prospective correction, motion resulted in severe lipid contamination in the MR spectra. With prospective correction, the quality of spinal cord MR spectra in the presence of motion was similar to that obtained in the absence of motion, with comparable spectral signal‐to‐noise ratio and linewidth and no significant lipid contamination. Conclusion: Prospective motion and B0 correction allow acquisition of good‐quality MR spectra in the human cervical spinal cord in the presence of motion. This new technique should facilitate reliable acquisition of spinal cord MR spectra in both research and clinical settings. [ABSTRACT FROM AUTHOR]

An idealized aquaplanet moist global atmospheric model with realistic radiative transfer but no clouds and no convective parameterization is found to possess multiple climate equilibria. When forced symmetrically about the equator, in some cases the Inter Tropical Convergence Zone (ITCZ) migrates to an off‐equatorial equilibrium position. Mechanism denial experiments prescribing relative humidity imply that radiation‐circulation coupling is essential to this instability. The cross‐equatorial asymmetry occurs only when the underlying slab ocean is sufficiently deep and the atmosphere's spectral dynamical core is sufficiently coarse (∼T170 or less with our control parameters). At higher resolutions, initializing with an asymmetric state indicates metastability with very slow (thousands of days) return to hemispheric symmetry. There is some sensitivity to the model timestep, which affects the time required to transition to the asymmetric state, with little effect on the equilibrium climate. The instability is enhanced when the planetary boundary layer scheme favors deeper layers or by a prescribed meridional heat transport away from the equator within the slab. The instability is not present when the model is run with a convective parameterization scheme commonly utilized in idealized moist models. We argue that the instability occurs when the asymmetric heating associated with a spontaneous ITCZ shift drives a circulation that rises poleward of the perturbed ITCZ. These results serve as a warning of the potential for instability and non‐uniqueness of climate that may complicate studies with idealized models of the tropical response to perturbations in forcing. Plain Language Summary: Much of the rainfall in the tropics occurs in the Intertropical Convergence Zones (ITCZs). These regions are associated with the convergence of surface winds, which produces the rising air required to feed the Hadley cells. The ITCZ location is known to be determined by the spatial distribution of atmospheric heating as the Hadley cells act to erase thermal imbalance within the tropics. With hemispherically symmetric heating, a symmetric equatorial ITCZ is expected. However, it is shown in this paper that changes in the ITCZ location affect the distribution of the radiative cooling of the atmosphere through changes in the water vapor distribution, which may make the equatorial ITCZ unstable under some circumstances. In this situation, two alternative climates with the ITCZ shifted into either one of the hemispheres exist. This instability may play an important role for understanding the distribution of tropical precipitation and the potential for the existence of multiple climates for the same set of external conditions. Key Points: The equatorial ITCZ can be destabilized by radiation‐circulation coupling in a hemispherically symmetric aquaplanet modelAs the ITCZ drifts off the equator two different asymmetric equilibria may exist under symmetric forcing and boundary conditionsA theory is proposed based on the energy flux equator sensitivity to the perturbed asymmetric heating when the ITCZ moves off the equator [ABSTRACT FROM AUTHOR]

LGBTQ+ individuals face unique barriers to participation in ecology. Such barriers are particularly relevant during fieldwork, including physical and discriminatory risks, increased isolation and noninclusive infrastructure.To make science and fieldwork more accessible to LGBTQ+ people, we must consider safety and survival needs along with personal LGBTQ+ affirmation. In this paper, we discuss alleviating barriers to participation in field ecology, identify best practices for institutions and provide advice for LGBTQ+ field researchers and heterosexual advocates.Synthesis and applications. We recommend that mentors and institutions take action on the safety, financial, medical and administrative support needed by field researchers who are lesbian, gay, bisexual, trans, queer or other marginalized gender and sexual identities (LGBTQ+) field researchers. We also suggest that LGBTQ+ field ecologists prioritize their wellbeing and safety, and recommend maintaining connection to LGBTQ+ communities and identities during isolating fieldwork. [ABSTRACT FROM AUTHOR]

Background: Spinal cord damage is a hallmark of Friedreich's ataxia (FRDA), but its progression and clinical correlates remain unclear. Objective: The objective of this study was to perform a characterization of cervical spinal cord structural damage in a large multisite FRDA cohort. Methods: We performed a cross‐sectional analysis of cervical spinal cord (C1–C4) cross‐sectional area (CSA) and eccentricity using magnetic resonance imaging data from eight sites within the ENIGMA‐Ataxia initiative, including 256 individuals with FRDA and 223 age‐ and sex‐matched control subjects. Correlations and subgroup analyses within the FRDA cohort were undertaken based on disease duration, ataxia severity, and onset age. Results: Individuals with FRDA, relative to control subjects, had significantly reduced CSA at all examined levels, with large effect sizes (d > 2.1) and significant correlations with disease severity (r < −0.4). Similarly, we found significantly increased eccentricity (d > 1.2), but without significant clinical correlations. Subgroup analyses showed that CSA and eccentricity are abnormal at all disease stages. However, although CSA appears to decrease progressively, eccentricity remains stable over time. Conclusions: Previous research has shown that increased eccentricity reflects dorsal column (DC) damage, while decreased CSA reflects either DC or corticospinal tract (CST) damage, or both. Hence our data support the hypothesis that damage to the DC and damage to CST follow distinct courses in FRDA: developmental abnormalities likely define the DC, while CST alterations may be both developmental and degenerative. These results provide new insights about FRDA pathogenesis and indicate that CSA of the cervical spinal cord should be investigated further as a potential biomarker of disease progression. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

In the central nervous system (CNS), execution of programmed cell death (PCD) is crucial for proper neurodevelopment. However, aberrant activation of these pathways in adult CNS leads to neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). How a cell dies is critical, as it can drive local immune activation and tissue damage. Classical apoptosis engages several mechanisms to evoke "immunologically silent" responses, whereas other forms of programmed death such as pyroptosis, necroptosis, and ferroptosis release molecules that can potentiate immune responses and inflammation. In ALS, a fatal neuromuscular disorder marked by progressive death of lower and upper motor neurons, several cell types in the CNS express machinery for multiple PCD pathways. The specific cell types engaging PCD, and ultimate mechanisms by which neuronal death occurs in ALS are not well defined. Here, we provide an overview of different PCD pathways implicated in ALS. We also examine immune activation in ALS and differentiate apoptosis from necrotic mechanisms based on downstream immunological consequences. Lastly, we highlight therapeutic strategies that target cell death pathways in the treatment of neurodegeneration and inflammation in ALS. [ABSTRACT FROM AUTHOR]

Objective: We aimed to determine the prevalence of abnormal umbilical artery (UA), uterine artery (UtA), middle cerebral artery (MCA) and cerebroplacental ratio (CPR) Doppler, and their relationship with adverse perinatal outcomes in women undergoing routine antenatal care in the third trimester. Design Prospective cohort. Setting: Kagadi Hospital, Uganda. Population: Non‐anomalous singleton pregnancies. Methods: Women underwent an early dating ultrasound and a third‐trimester Doppler scan between 32 and 40 weeks of gestation, from 2018 to 2020. We handled missing data using multiple imputation and analysed the data using descriptive methods and a binary logistic regression model. Main outcome measures: Composite adverse perinatal outcome (CAPO), perinatal death and stillbirth. Results: We included 995 women. The mean gestational age at Doppler scan was 36.9 weeks (SD 1.02 weeks) and 88.9% of the women gave birth in a health facility. About 4.4% and 5.6% of the UA pulsatility index (PI) and UtA PI were above the 95th percentile, whereas 16.4% and 10.4% of the MCA PI and CPR were below the fifth percentile, respectively. Low CPR was strongly associated with stillbirth (OR 4.82, 95% CI 1.09–21.30). CPR and MCA PI below the fifth percentile were independently associated with CAPO; the association with MCA PI was stronger in small‐for‐gestational‐age neonates (OR 3.75, 95% CI 1.18–11.88). Conclusion: In late gestation, abnormal UA PI was rare. Fetuses with cerebral blood flow redistribution were at increased risk of stillbirth and perinatal complications. Further studies examining the predictive accuracy and effectiveness of antenatal Doppler ultrasound screening in reducing the risk of perinatal deaths in low‐ and middle‐income countries are warranted. Blood flow redistribution to the fetal brain is strongly associated with stillbirths in low‐resource settings. Blood flow redistribution to the fetal brain is strongly associated with stillbirths in low‐resource settings. This article includes Author Insights, a video abstract available at https://vimeo.com/bjogabstracts/authorinsights17115. [ABSTRACT FROM AUTHOR]

Background: Staphylococcus aureus cause diseases both in humans and animals. These diseases range from mild to fatal infections thus necessitating development of a specific molecular method for detection of pathogenic S. aureus. Objectives: To identify and analyze genetic profile of pathogenic S. aureus using bacteriophage based genetic biomarkers. Methods: Using culture and biochemical methods, 148 S. aureus (87 %) were isolated from 170 raw milk samples taken from 10 dairy farms in Marsabit and Isiolo counties in Northern Kenya between June 2016 and February 2017. The samples were collected directly from dairy lactating cows previously diagnosed with S. aureus in a follow‐up study. The isolates were analyzed by PCR and sequencing of beta hemolysin (hlb) gene. The genetic relationship between five Kenyan S. aureus isolates and five isolates previously identified was inferred. Results: From the 96 isolates screened for hlb gene, 75 (78.1%) tested positive. Some of the positive isolates yielded a band size of 975 bp, while others 1100 bp. Through Basic Local Alignment Search Tool (BLAST) search analysis, the two different band sizes (975 bp and 1100 bp) were both confirmed to be hlb gene from S. aureus isolates indicating that the difference in band size may have been due to deletions that were detected in the 975 bp hlb gene. Some S. aureus isolates from Kenya appeared to be closely related to isolates from other parts of the world, while some showed a distant relationship. Conclusions: Phage‐derived hlb gene is a suitable molecular marker for detection of pathogenic S. aureus. [ABSTRACT FROM AUTHOR]

Background: Non‐invasive assessment of maladaptive innate immune responses in the brains of Alzheimer's disease (AD) patients is a critical unmet need; such techniques have the potential to not only improve diagnosis and disease monitoring, but also serve as endpoints in clinical trials of novel therapeutics. Positron emission tomography (PET) imaging of the translocator protein 18 kDa (TSPO) is a widely used experimental approach for assessing inflammation in vivo but is limited by its lack of cell specificity and inability to discriminate between beneficial and adverse immune responses. We developed the first PET probe targeting triggering receptor expressed on myeloid cells 1 (TREM1) and demonstrated its ability to specifically detect CNS‐infiltrating pathogenic peripheral myeloid cells (e.g., macrophages, monocytes, neutrophils) in the context of neurological disease. Herein, we assess the utility of TREM1‐PET compared to TSPO‐PET for detecting innate immune responses in the 5XFAD mouse model of AD. Method: 5XFAD and wild‐type (WT) 6–7‐month‐old mice underwent 10 min static TREM1‐ and TSPO‐PET/CT imaging. TSPO‐PET was performed 50–60 minutes post‐intravenous injection of [18F]GE‐180 (175.1±13.8 μCi). TREM1‐PET was performed 20 hours following intravenous injection of [64Cu]TREM1‐mAb (94.75±4.96 μCi). Tracer binding was quantified in the cortex, hippocampus, thalamus, and whole brain using a semi‐automated brain atlas‐based approach. CD68 immunostaining of brain tissue was performed to assess microglia/macrophage activation. Result: TREM1‐PET quantification revealed significantly increased [64Cu]TREM1‐mAb binding in the hippocampus (1.37‐vs‐1.14 %ID/g, p=0.02) and thalamus (1.00‐vs‐0.76 %ID/g, p=0.04) of 6–7‐month‐old 5XFAD compared to WT mice (Fig 1A). Elevated TREM1‐PET binding was observed in the cortex (1.77‐vs‐1.62 %ID/g, p=0.14) and whole brain (1.64‐vs‐1.46 %ID/g, p=0.08) but did not reach significance. TSPO‐PET imaging demonstrated significantly increased [18F]GE‐180 binding in all regions (cortex: 2.36‐vs‐1.48 %ID/g; p=0.0003, hippocampus: 2.59‐vs‐1.52 %ID/g, p<0.0001, thalamus: 2.18‐vs‐1.20 %ID/g, p<0.0001, whole brain: 2.55‐vs‐1.66 %ID/g, p=0.0003, Fig. 1B). CD68 staining confirmed increased microglia/macrophage activation in cortical, hippocampal, and thalamic regions (Fig 2). Conclusion: Differential regional binding patterns were observed with TREM1‐ and TSPO‐PET imaging. Notably, increased TREM1‐PET signal in 5XFAD animals suggests a role for peripheral myeloid cells in AD. Longitudinal whole‐body TREM1‐ and TSPO‐PET imaging in this model is currently underway. [ABSTRACT FROM AUTHOR]

The paper estimates the likely effects of the AfCFTA on the east african community(EAC) countries. The paper adopts two approaches. First, a trend analysis of the EAC exports and imports to and from the rest of Africa and the world at large using data from the Trade Map database. Second, we use the WITS‐SMART analytical framework. It is established that the EAC countries mainly export agricultural commodities and products, and minerals, which are not likely to be readily imported by the rest of Africa. This is because between 2001 and 2018, the African continent heavily relied on external markets for exports and imports. Therefore, signing the AfCFTA agreement is a welcome step, but it may not necessarily increase EAC trade with the rest of African and intra‐African trade. Results for the trade effects suggest a mixed effect among the EAC countries. All the EAC countries incur tariff revenue losses, although this varies in absolute amounts and proportions. Whereas Uganda and Burundi experience positive welfare effects, Kenya, Tanzania, and Rwanda experience negative welfare effects. The policy implications include: a need to build capacity for production; pursue product diversification and sophistication; innovate and attract investments; adopt high international products standards; and target industrialization as a must. [ABSTRACT FROM AUTHOR]

The evolution of seed size may be influenced by intrinsic attributes of populations, such as mating system and extrinsic factors, such as climate. Several hypotheses propose that the evolution of self‐fertilization from an outcrossing progenitor will be accompanied by a reduction in seed size, but this prediction has not been rigorously tested. Many studies report that the mean seed size of populations or taxa is associated with long‐term climate conditions. Here, we examined the effects on seed size of both mating system and climate within a single genus.In the California wildflower genus, Clarkia (Onagraceae), we sampled seeds from 58 populations representing three pairs of sister taxa; each pair included a predominantly outcrossing and a facultatively selfing taxon. We then examined the independent effects on population mean seed size of mating system, elevation, long‐term (30‐year) climate conditions, and climate anomalies (the deviation between conditions in the year of collection and the long‐term mean), focusing on maximum monthly temperature (Tmax), cumulative moisture deficit and cumulative precipitation (PPT) during Clarkia's growing season (fall, winter and spring).In each taxon pair, the selfing taxon had smaller seeds than the outcrosser. Local, long‐term (1921–1980 and 1981–2000) mean Tmax, PPT and elevation were independently and negatively associated with seed size. Long‐term means for Tmax and PPT explain geographical variation in seed size better than climate anomalies in the year of collection.Synthesis. We corroborated two key hypotheses concerning the drivers of geographical variation in mean seed size. Small seeds in Clarkia co‐evolve with selfing (although the mechanism remains elusive) and in response to chronically warm and wet conditions. The effect of long‐term mean precipitation on seed size differs qualitatively from the effect of precipitation anomalies; relatively large seeds are produced in populations experiencing wetter‐than‐normal years. Ongoing climate change may therefore generate conflicting selection on seed size in Clarkia: intensifying drought is likely to lead to an evolutionary increase in seed size due to its effects on seedling survivorship, while climate‐driven declines in pollinators or selection favouring more rapid reproduction may promote the evolution of self‐pollination, facilitating the evolution of smaller seeds. [ABSTRACT FROM AUTHOR]

Black soldier fly (BSF) larvae, Hermetia illucens L. (Diptera: Stratiomyidae), bio‐convert organic side streams into high‐quality biomass, the composition of which largely depends on the side stream used. In the present study, BSF larvae were reared on feed substrates composed of dried brewers' spent grains, each supplemented with either water, waste brewer's yeast, or a mixture of waste brewer's yeast and cane molasses to obtain 12 different substrates: barley/water, barley/yeast, barley/yeast/molasses, malted barley/water, malted barley/yeast, malted barley/yeast/molasses, malted corn/water, malted corn/yeast, malted corn/yeast/molasses, sorghum‐barley/water, sorghum‐barley/yeast, and sorghum‐barley/yeast/molasses. The crude protein, fat, ash, and mineral contents of the BSF larvae fed each feed substrate were quantified by chemical analyses. The effect of substrate, supplementation, and their interaction on crude protein, fat, and ash contents of BSF larval body composition was significant. Calcium, phosphorus, and potassium were the most abundant macrominerals in the larvae and their concentrations differed significantly among substrates. These findings provide important information to support the use of BSF larval meal as potential new source of nutrient‐rich and sustainable animal feed ingredients to substitute expensive and scarce protein sources such as fishmeal and soya bean meal. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells are at the forefront of immunotherapies, as they have potent innate cytolytic effects on cancer cells. The success of NK cell therapies requires that they overcome immunosuppression in the tumor microenvironment. Tumors produce immunosuppressive factors like transforming growth factor beta (TGF‐β) that inhibit the effector functions of NK cells. Silencing of TGF‐beta signaling in NK cells is a potential approach to enhance their functions. However, transfection of NK cells by conventional methods is challenging. Here, we report the development of a nanoparticle (NP) system that delivers small interfering RNA for the TGF‐β receptor 2 (TGFBR2) into NK cells to restore their activation against cancer cells. Manganese dioxide NPs were synthesized by the reduction of potassium permanganate by poly (allylamine), which effectively complexed siRNA and protected it from degradation. The NPs were cytocompatible with NK cells and, upon loading with TGFBR2 siRNA, resulted in a 90% knockdown of the TGFBR2 receptor. NP‐mediated TGFBR2 receptor knockdown protected NK cells against TGF‐β suppression, which was studied in both two‐dimensional and three‐dimensional lung cancer cell culture systems. Namely, NK cells treated with TGFBR2 siRNA loaded NPs demonstrated higher interferon gamma production, infiltration, and killing of lung cancer cells compared with control NK cells. This study demonstrates the feasibility of NP‐mediated RNA interference in NK cells to increase their resilience to the immunosuppressive environments in solid tumors. [ABSTRACT FROM AUTHOR]

Objective: Prostate cancer (PC) and its treatment often result in chronic, negative side-effects that affect both patients and their romantic partners. Illness uncertainty is a chronic stressor that impacts PC patients and their partners and, if left unmanaged, predicts decreased interpersonal functioning and quality of life (QOL) after treatment is complete. This study explored associations among psychosocial constructs, measured from both partners during the first year following a PC diagnosis, to better understand both partners' experiences and identify potential intervention targets for improving QOL.Methods: Couples (N = 165) in which one partner was undergoing treatment for PC were recruited from the Duke University Medical Center of Urology. Patients and their partners were surveyed at four time points: diagnosis and 1-, 6-, and 12-months post treatment. An Actor-Partner Interdependence Model (APIM) framework was used to examine associations among perceived partner support, nonsupportive behaviors, illness uncertainty, relationship satisfaction, and physical and mental QOL.Results: Partners feeling more supported at diagnosis was related to patients feeling more supported at 6 months. When patients' illness uncertainty decreased between diagnosis and 1 month, partners reported feeling more supported and engaging in fewer nonsupportive behaviors at 6-months post-treatment. Finally, partners' reports of support at 6 months predicted patients' 12-month ratings of physical and mental QOL and relationship satisfaction.Conclusions: Findings highlight psychological interdependence between PC patients and their partners. Future interventions to improve long-term QOL in couples facing PC may benefit by targeting both partner support and illness uncertainty. [ABSTRACT FROM AUTHOR]

We document the configuration and emergent simulation features from the Geophysical Fluid Dynamics Laboratory (GFDL) OM4.0 ocean/sea ice model. OM4 serves as the ocean/sea ice component for the GFDL climate and Earth system models. It is also used for climate science research and is contributing to the Coupled Model Intercomparison Project version 6 Ocean Model Intercomparison Project. The ocean component of OM4 uses version 6 of the Modular Ocean Model and the sea ice component uses version 2 of the Sea Ice Simulator, which have identical horizontal grid layouts (Arakawa C-grid). We follow the Coordinated Ocean-sea ice Reference Experiments protocol to assess simulation quality across a broad suite of climate-relevant features. We present results from two versions differing by horizontal grid spacing and physical parameterizations: OM4p5 has nominal 0.5° spacing and includes mesoscale eddy parameterizations and OM4p25 has nominal 0.25° spacing with no mesoscale eddy parameterization. Modular Ocean Model version 6 makes use of a vertical Lagrangian-remap algorithm that enables general vertical coordinates. We show that use of a hybrid depth-isopycnal coordinate reduces the middepth ocean warming drift commonly found in pure z* vertical coordinate ocean models. To test the need for the mesoscale eddy parameterization used in OM4p5, we examine the results from a simulation that removes the eddy parameterization. The water mass structure and model drift are physically degraded relative to OM4p5, thus supporting the key role for a mesoscale closure at this resolution. [ABSTRACT FROM AUTHOR]

Abstract: Using a nonhydrostatic model based on a version of Geophysical Fluid Dynamics Laboratory's FV3 dynamical core at a cloud‐resolving resolution in radiative‐convective equilibrium (RCE) configuration, the sensitivity of the mean RCE climate to the magnitude and scale‐selectivity of the divergence damping is explored. Divergence damping is used to reduce small‐scale noise in more realistic configurations of this model. This sensitivity is tied to the strength (and width) of the convective updrafts, which decreases (increases) with increased damping and acts to organize the convection, dramatically drying out the troposphere and increasing the outgoing longwave radiation. Increased damping also results in a much‐broadened precipitation probability distribution and larger extreme values, as well as reduction in cloud fraction, which correspondingly decreases the magnitude of shortwave and longwave cloud radiative effects. Solutions exhibit a monotonic dependence on the strength of the damping and asymptotically converge to the inviscid limit. While the potential dependence of RCE simulations on resolution and microphysical assumptions are generally appreciated, these results highlight the potential significance of the choice of subgrid numerical diffusion in the dynamical core. [ABSTRACT FROM AUTHOR]

The striatum is a well‐known region affected in Huntington disease (HD). However, other regions, including the visual cortex, are implicated. We have identified previously an abnormal energy response in the visual cortex of patients at an early stage of HD using 31P magnetic resonance spectroscopy (31P MRS). We therefore sought to further characterize these metabolic alterations with 1H MRS using a well‐validated semi‐localized by adiabatic selective refocusing (semi‐LASER) sequence that allows the measurement of an expanded number of neurometabolites. Ten early affected patients [Unified Huntington Disease Rating Scale (UHDRS), total motor score = 13.6 ± 10.8] and 10 healthy volunteers of similar age and body mass index (BMI) were recruited for the study. We performed 1H MRS in the striatum – the region that is primarily affected in HD – and the visual cortex. The protocol allowed a reliable quantification of 10 metabolites in the visual cortex and eight in the striatum, compared with three to five metabolites in previous 1H MRS studies performed in HD. We identified higher total creatine (p < 0.05) in the visual cortex and lower glutamate (p < 0.001) and total creatine (p < 0.05) in the striatum of patients with HD compared with controls. Less abundant neurometabolites [glutamine, γ‐aminobutyric acid (GABA), glutathione, aspartate] showed similar concentrations in both groups. The protocol allowed the measurement of several additional metabolites compared with standard vendor protocols. Our study points to early changes in metabolites involved in energy metabolism in the visual cortex and striatum of patients with HD. Decreased striatal glutamate could reflect early neuronal dysfunction or impaired glutamatergic neurotransmission. [ABSTRACT FROM AUTHOR]

Background: Chronic activation of macrophages/microglia plays a critical role in the onset and progression of neurological diseases, including Alzheimer's. While PET imaging could enable non‐invasive visualization and quantification of activated macrophages/microglia in vivo, most available PET tracers are nonspecific for macrophages/microglia (Lambert, 2009). To address this need, we developed [18F]OP‐801, a synthetic hydroxyl dendrimer‐based PET tracer that is selectively (>95%) taken up by reactive macrophages/microglia across the blood‐brain barrier (Alnasser, 2018). Here, we evaluated the ability of [18F]OP‐801 to detect activated macrophages/microglia in the 5XFAD murine model of Alzheimer's compared to an established neuroinflammation imaging approach (translocator protein 18 kDa [TSPO]‐PET, using [18F]GE180). Method: [18F]OP‐801 (150‐250 μCi) was injected intravenously into female 5XFAD (TG) mice (n=12) and age/sex‐matched wild types (WT, n=7) at 3.75 and 5 months old. Sensitivity of [18F]OP‐801 was compared to [18F]GE180 by assessing brain signal‐to‐background ratios. [18F]GE180 (150‐250 μCi) was administered to a subset of TG (n=5) and WT (n=4) 3.75‐months‐old mice. Static 10‐minute PET/CT images were acquired at 50‐60 minutes post‐injection for both tracers. VivoQuant brain atlas was fit to CT images and fused to PET to quantify uptake in specific brain regions. Result: In this model, macrophage/microglial activation is associated with amyloid plaque formation and can be detected using immunohistochemistry between 2‐4 months. Image quantification revealed 3‐fold higher PET signal in 3.75‐months‐old TG compared to WT mice using [18F]OP‐801, whereas [18F]GE180 signal provided no significant difference in brain regions known to contain activated microglia: cortex and hippocampus (Figure 1, Table 1). Significant differences in [18F]OP‐801 uptake were observed between 5‐months‐old TG and WT mice in cortex (p=0.005) (TG: 0.26±0.095%ID/g, WT: 0.11±0.041%ID/g), hippocampus (p=0.017) (TG: 0.18±0.065%ID/g, WT: 0.10±0.026%ID/g) and whole brain (p=0.004) (TG: 0.20±0.082%ID/g, WT: 0.10±0.039%ID/g). TG had almost 5‐fold higher [18F]OP‐801 signal compared to WT mice (Table 2). Conclusion: These results suggest that [18F]OP‐801 can detect early stage neuroinflammation with higher sensitivity than TSPO‐PET. We are currently replicating this study in a larger cohort of 5XFAD mice to correlate PET image findings with immunohistochemistry. [18F]OP‐801 is shows promise for visualizing the progression of neuroinflammation with high specificity and sensitivity, warranting further preclinical investigation. [ABSTRACT FROM AUTHOR]

Background: To understand whether patient-reported experiences with lung cancer may create teachable moments (TM) for their relatives as evidenced by shifts in their risk perceptions, affective response, and self-image and in turn, motivation to quit smoking.Methods: Patients at a comprehensive cancer center (n = 152) completed a survey within 6 months of lung cancer diagnosis to assess their cancer-related symptoms and openness and enumerated relatives who were smokers. Relative smokers (n = 218) then completed a survey assessing their risk perceptions, affective response, and self-image as a smoker related to the patient's diagnosis (TM mechanisms), and their motivation to quit smoking. Cross-sectional mediation and moderation analyses were conducted to explore the links between patient-reported experiences, and relatives' TM mechanisms, and motivation to quit smoking.Results: Relative-reported affect was a significant mediator of the association between patient-reported symptoms and relative smoker's desire to quit. Relatives' self-image was a significant moderator of the association between patient-reported symptoms and relative smoker's desire to quit, such that patients' reported symptoms were associated with relatives' desire to quit only when the relative smoker reported a generally positive self-image as a smoker. No evidence was found for moderated mediation. However, the link between symptoms and negative affect was moderated by perceptions of risk.Conclusion: Whether smokers experience a family member's lung cancer as a TM is influenced by multiple interrelated cognitive and affective factors that warrant further exploration. Clearer understanding of these factors could inform how to re-invigorate and sustain this motivation to promote concrete actions toward smoking cessation. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

ABSTRACT While the effects of disc degeneration on compression and rotation motions have been studied, there is no data for shear loading. Clinical research has shown that those with low back pain (a potential consequence of degeneration) experience a 75% greater lateral shear force than those without it. Therefore, the aim was to compare the effect of degeneration on spine segment stiffness and phase angle in each of six degree of freedom (6DOF) loading directions. Fourteen intact functional spinal units (FSU) were dissected from human lumbar spines (mean (SD) age 76.2 (11) years, Thompson grades 3 ( N = 5, mild), 4 ( N = 6, moderate), 5 ( N = 3, severe)). Each FSU was tested in ±6DOFs while subjected to a physiological preload, hydration, and temperature (37°C) conditions in a hexapod robot. A one-way ANOVA between degenerated groups was performed on stiffness and phase angle for each DOF. Significant differences in stiffness were found between mild and moderate degenerative groups in lateral shear ( p = 0.001), and axial rotation ( p = 0.001), where moderate degeneration had decreased stiffness. For phase angle, significant differences were seen in anterior shear ( p = 0.017), and axial rotation ( p = 0.026), where phase angle for mild degeneration was less than moderate. Trends of stiffness and phase angle changes between degenerative groups were similar within each DOF. Clinically, the identification of the DOFs that are most affected by degeneration could be used in rehabilitation to improve supplemental stabilization of core muscle groups. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1399-1409, 2016. [ABSTRACT FROM AUTHOR]

Objectives: Prostate cancer may affect quality of life in men diagnosed as well as their spouses. Changes in health may disrupt the couple's relationship functioning which disrupts recovery. This study examined how mental and physical health relates to relationship satisfaction for couples at diagnosis through the year following treatment.Methods: Patients with stage I-II prostate cancer and their spouses (N = 159 couples) were recruited from a urology clinic and completed questionnaires at diagnosis, 1 month, 6 months, and 12 months post prostatectomy on demographics, mental and physical health quality of life, and relationship satisfaction. The Actor-Partner Interdependence Model was employed to examine effects of each partners' mental and physical health on their own and their partner's relationship satisfaction.Results: Patients and spouses had declined mental and physical health at 1 month post-surgery. Health improved at 6 and 12 months but did not fully return to pre-surgery levels. Actor effects showed that patient's physical health consistently predicted own relationship satisfaction. Both patient's and spouse's mental health consistently related to their own relationship satisfaction. Partner effects showed that patient's and spouse's physical health had an effect on each other's relationship satisfaction at 1 month. Spouse's mental health predicted patient's relationship satisfaction throughout the year following treatment.Conclusion: The effects of patient and spouse mental and physical health quality of life on their own as well as their partner's relationship satisfaction differed across time which will inform psychosocial interventions for couples with prostate cancer. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Natural auditory scenes possess highly structured statistical regularities, which are dictated by the physics of sound production in nature, such as scale-invariance. We recently identified that natural water sounds exhibit a particular type of scale invariance, in which the temporal modulation within spectral bands scales with the centre frequency of the band. Here, we tested how neurons in the mammalian primary auditory cortex encode sounds that exhibit this property, but differ in their statistical parameters. The stimuli varied in spectro-temporal density and cyclo-temporal statistics over several orders of magnitude, corresponding to a range of water-like percepts, from pattering of rain to a slow stream. We recorded neuronal activity in the primary auditory cortex of awake rats presented with these stimuli. The responses of the majority of individual neurons were selective for a subset of stimuli with specific statistics. However, as a neuronal population, the responses were remarkably stable over large changes in stimulus statistics, exhibiting a similar range in firing rate, response strength, variability and information rate, and only minor variation in receptive field parameters. This pattern of neuronal responses suggests a potentially general principle for cortical encoding of complex acoustic scenes: while individual cortical neurons exhibit selectivity for specific statistical features, a neuronal population preserves a constant response structure across a broad range of statistical parameters. [ABSTRACT FROM AUTHOR]

Motivated by findings that energetically consistent subgrid dissipation schemes can improve eddy-permitting ocean simulations, this work investigates the impact of the subgrid dissipation scheme on low-resolution atmospheric dynamical cores. A kinetic energy-conserving dissipation scheme is implemented in the model adding a negative viscosity term that injects back into the eddy field the kinetic energy dissipated by horizontal hyperdiffusion. The kinetic energy-conserving scheme enhances numerical convergence when horizontal resolution is changed with fixed vertical resolution and gives superior low-resolution results. Improvements are most obvious for eddy kinetic energy but also found in other fields, particularly with strong or little scale-selective horizontal hyperdiffusion. One advantage of the kinetic energy-conserving scheme is that it reduces the sensitivity of the model to changes in the subgrid dissipation rate, providing more robust results. [ABSTRACT FROM AUTHOR]

Purpose To determine whether neurochemical concentrations obtained at two MRI sites using clinical 3T scanners can be pooled when a highly optimized, nonvendor short-echo, single-voxel proton MRS pulse sequence is used in conjunction with identical calibration and quantification procedures. Methods A modified semi-LASER sequence ( TE = 28 ms) was used to acquire spectra from two brain regions (cerebellar vermis and pons) on two Siemens 3T scanners using the same B0 and B1 calibration protocols from two different cohorts of healthy volunteers ( N = 24-33 per site) matched for age and body mass index. Spectra were quantified with LCModel using water scaling. Results The spectral quality was very consistent between the two sites and allowed reliable quantification of at least 13 metabolites in the vermis and pons compared with 3-5 metabolites in prior multisite magnetic resonance spectroscopy trials using vendor-provided sequences. The neurochemical profiles were nearly identical at the two sites and showed the feasibility to detect interindividual differences in the healthy brain. Conclusion Highly reproducible neurochemical profiles can be obtained on different clinical 3T scanners at different sites, provided that the same, optimized acquisition and analysis techniques are used. This will allow pooling of multisite data in clinical studies, which is particularly critical for rare neurological diseases. Magn Reson Med 73:1718-1725, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Spinocerebellar ataxias (SCAs) belong to polyglutamine repeat disorders and are characterized by a predominant atrophy of the cerebellum and the pons. Proton magnetic resonance spectroscopy (1H MRS) using an optimized semiadiabatic localization by adiabatic selective refocusing (semi-LASER) protocol was performed at 3 T to determine metabolite concentrations in the cerebellar vermis and pons of a cohort of patients with SCA1 (n = 16), SCA2 (n = 12), SCA3 (n = 21), and SCA7 (n = 12) and healthy controls (n = 33). Compared with controls, patients displayed lower total N-acetylaspartate and, to a lesser extent, lower glutamate, reflecting neuronal loss/dysfunction, whereas the glial marker, myoinositol ( myo-Ins), was elevated. Patients also showed higher total creatine as reported in Huntington's disease, another polyglutamine repeat disorder. A strong correlation was found between the Scale for the Assessment and Rating of Ataxia and the neurometabolites in both affected regions of patients. Principal component analyses confirmed that neuronal metabolites (total N-acetylaspartate and glutamate) were inversely correlated in the vermis and the pons to glial ( myo-Ins) and energetic (total creatine) metabolites, as well as to disease severity (motor scales). Neurochemical plots with selected metabolites also allowed the separation of SCA2 and SCA3 from controls. The neurometabolic profiles detected in patients underlie cell-specific changes in neuronal and astrocytic compartments that cannot be assessed by other neuroimaging modalities. The inverse correlation between metabolites from these two compartments suggests a metabolic attempt to compensate for neuronal damage in SCAs. Because these biomarkers reflect dynamic aspects of cellular metabolism, they are good candidates for proof-of-concept therapeutic trials. © 2015 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Failures in trials for Alzheimer's disease (AD) may be attributable to inadequate dosing, population selection, drug inefficacy, or insufficient design optimization. The Coalition Against Major Diseases (CAMD) was formed in 2008 to develop drug development tools (DDT) to expedite drug development for AD and Parkinson's disease.1 CAMD led a process that successfully advanced a clinical trial simulation (CTS) tool for AD through the formal regulatory review process at the US Food and Drug Administration (FDA) and European Medicines Agency (EMA). [ABSTRACT FROM AUTHOR]

BACKGROUND Few studies to date have used the cancer diagnosis as a teachable moment to promote healthy behavior changes in survivors of cancer and their family members. Given the role of obesity in the primary and tertiary prevention of breast cancer, the authors explored the feasibility of a mother-daughter weight loss intervention. METHODS A randomized controlled trial of a mailed weight loss intervention was undertaken among 68 mother-daughter dyads (n = 136), each comprised of a survivor of breast cancer (AJCC stage 0-III) and her adult biological daughter. All women had body mass indices ≥ 25 kg/m2 and underwent in-person assessments at baseline, 6 months, and 12 months, with accelerometry and exercise capacity performed on a subset of individuals. All women received a personalized workbook and 6 newsletters over a 1-year period that promoted weight loss; exercise; and a nutrient-rich, low-energy density diet. A total of 25 dyads received individually tailored instruction (INDIVIDUAL), 25 dyads received team-tailored instruction (TEAM), and 18 dyads received standardized brochures (CONTROL). RESULTS The trial met its accrual target, experienced 90% retention, and caused no serious adverse events. Significant differences in baseline to 12-month changes were observed between INDIVIDUAL versus CONTROL mothers for body mass index, weight, and waist circumference (WC); significant differences also were observed in the WC of corresponding daughters ( P < .05). Significant differences were found between INDIVIDUAL versus CONTROL and TEAM versus CONTROL dyads for WC ( P = .0002 and .018, respectively), minutes per week of physical activity ( P = .031 and .036, respectively), and exercise capacity ( P = .047 for both). CONCLUSIONS Significant improvements in lifestyle behaviors and health outcomes are possible with tailored print interventions directed toward survivors of cancer and their family members. For greater impact, more research is needed to expand this work beyond the mother-daughter dyad. Cancer 2014;120:2522-2534. © 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. [ABSTRACT FROM AUTHOR]

The article reviews the book "The Return of the Chaos Monsters, and Other Backstories of the Bible," by Gregory Mobley.

Background: Alcohol is heavily consumed in sub-Saharan Africa and affects HIV transmission and treatment and is difficult to measure. Our goal was to examine the test characteristics of a direct metabolite of alcohol consumption, phosphatidylethanol (PEth). Methods: Persons infected with HIV were recruited from a large HIV clinic in southwestern Uganda. We conducted surveys and breath alcohol concentration (BRAC) testing at 21 daily home or drinking establishment visits, and blood was collected on day 21 ( n = 77). PEth in whole blood was compared with prior 7-, 14-, and 21-day alcohol consumption. Results: (i) The receiver operator characteristic area under the curve (ROC-AUC) was highest for PEth versus any consumption over the prior 21 days (0.92; 95% confidence interval [CI]: 0.86 to 0.97). The sensitivity for any detectable PEth was 88.0% (95% CI: 76.0 to 95.6) and the specificity was 88.5% (95% CI: 69.8 to 97.6). (ii) The ROC-AUC of PEth versus any 21-day alcohol consumption did not vary with age, body mass index, CD4 cell count, hepatitis B virus infection, and antiretroviral therapy status, but was higher for men compared with women ( p = 0.03). (iii) PEth measurements were correlated with several measures of alcohol consumption, including number of drinking days in the prior 21 days (Spearman r = 0.74, p < 0.001) and BRAC ( r = 0.75, p < 0.001). Conclusions: The data add support to the body of evidence for PEth as a useful marker of alcohol consumption with high ROC-AUC, sensitivity, and specificity. Future studies should further address the period and level of alcohol consumption for which PEth is detectable. [ABSTRACT FROM AUTHOR]

An in vitro ruminal gas production study was conducted to assess the effect of yeast supplementation on rumen fermentation of tanniniferous tropical browse mixtures prepared by mixing Berchemia discolor with Acacia brevispica, Acacia elatior, Acacia mellifera, Balanites aegyptiaca, Grewia bicolor or Zizyphus mucronata in a 1:1 dry weight ratio. The six browse mixtures were incubated with buffered rumen fluid alone or supplemented with dried Japanese Sake yeast (JSY) or polyethylene glycol (PEG). Ruminal gas production characteristics were evaluated using the Gompertz equation. The JSY addition increased gas production volume ( P < 0.05) and numerically increased the maximum gas production rate constant. Time to reach the maximum gas production rate was shortened by PEG addition as compared to the JSY and control treatments. It is possible that JSY promoted the rumen microbial activity in addition to forming complexes with tannins thereby upgrading the in vitro ruminal digestion of tropical browse mixtures. [ABSTRACT FROM AUTHOR]

Deregulation of protein kinases is associated with numerous diseases, making them important targets for drug discovery. The majority of drugs target the catalytic site of these proteins, but due to the high level of similarity within the ATP binding sites of protein kinases, it is often difficult to achieve the required pharmacological selectivity. In this study, we describe the identification and subsequent analysis of water patterns in the ATP binding sites of 171 protein kinase structures, comprising 19 different kinases from various branches of the kinome, and demonstrate that structurally similar binding sites often have significantly different water patterns. We show that the observed variations in water patterns of different, but structurally similar kinases can be exploited in the structure-based design of potent and selective kinase inhibitors. Proteins 2011; © 2011 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The rapidly expanding market for monoclonal antibody and Fc-fusion-protein therapeutics has increased interest in improving the productivity of mammalian cell lines, both to alleviate capacity limitations and control the cost of goods. In this study, we evaluated the responses of an industrial CHO cell line producing an Fc-fusion-protein to hyperosmotic stress, a well-known productivity enhancer, and compared them with our previous studies of murine hybridomas (Shen and Sharfstein, Biotechnol Bioeng. 2006;93:132–145). In batch culture studies, cells showed substantially increased specific productivity in response to increased osmolarity as well as significant metabolic changes. However, the final titer showed no substantial increase due to the decrease in viable cell density. In fed batch cultures, hyperosmolarity slightly repressed the cellular growth rate, but no significant change in productivity or final titer was detected. To understand the transcriptional responses to increased osmolarity and relate changes in gene expression to increased productivity and repressed growth, proprietary CHO microarrays were used to monitor the transcription profile changes in response to osmotic stress. A set of osmotically regulated genes was generated and classified by extracting their annotations and functionalities from online databases. The gene list was compared with results previously obtained from similar studies of murine-hybridoma cells. The overall transcriptomic responses of the two cell lines were rather different, although many functional groups were commonly perturbed between them. Building on this study, we anticipate that further analysis will establish connections between productivity and the expression of specific gene(s), thus allowing rational engineering of mammalian cells for higher recombinant-protein productivity. © 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2010 [ABSTRACT FROM AUTHOR]

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In an attempt to engage students' higher-order thinking skills, we developed a documentary filmmaking project for our introduction to theology course. By documenting certain aspects of the theology of John Wesley and John Henry Newman (God, creation, revelation, Jesus, the church), students were able to delve deeply into these themes, better understanding them and their interrelationships. The project helped the students to actively practice historical theology, rather than passively learn about it through lectures. In addition, the project emphasized research skills, quality of writing and creative production, and a professional presentation at a screening. [ABSTRACT FROM AUTHOR]

The feeding value of five browse foliages ( Acacia brevispica, Acacia mellifera, Berchemia discolor, Zizyphus mucronata and Maerua angolensis) grown in semiarid area of Kenya were evaluated. Their chemical composition including polyphenolics and in vitro gas production characteristics were determined. The biological activity of the polyphenolics was assessed as the increases in gas production profiles and in vitro true dry matter (DM) and organic matter (OM) digestibility after in vitro incubation with or without addition of polyethylene glycol (PEG) as a tannin binding reagent. The intake and palatability ranking of the browse foliages by goats and sheep were also investigated. The browse foliages had variable crude protein content (149.5–248.6 g/kg DM) and variable content of neutral detergent fiber (205.1–424.0 g/kg DM). The content of total extractable tannins was generally low (2.4–34.8 g/kg DM). At 24 h of incubation, Z. mucronata produced the highest gas volume, while after 48 h of incubation, B. discolor produced the highest gas volume. M. angolensis had the least gas production potential within the browse foliages. Addition of PEG increased gas production except in A. mellifera and M. angolensis. However, PEG addition did not have any significant effect on in vitro true DM and OM digestibility except in B. discolor, which decreased. The rank order of preference (highest to least) for goats was A. brevispica, Z. mucronata, B. discolor, A. mellifera and M. angolensis while the rank order of preference for sheep was A. brevispica, B. discolor, A. mellifera, Z. mucronata and M. angolensis. The goats had higher intakes of all the browse foliages than sheep. The result of this study highlights the higher feeding value of the browse species as supplemental feed with low quality basal diet with both of animal species except M. angolensis. [ABSTRACT FROM AUTHOR]

Although trichoepitheliomas (TEs) are commonly regarded as benign tumors of follicular origin, the natural history of multiple familial trichoepitheliomas (MFT) and their risk for malignancy has been unclear. We describe a 57-year-old male with numerous skin-colored firm papules and plaques present on the central face since 6 years of age. Recently, some lesions had enlarged and ulcerated. Other family members were similarly affected. Biopsies from multiple lesions showed TEs both alone and associated with basal cell carcinoma (BCC) in the same section, suggesting the secondary development of BCCs within TEs. Many prior reports of BCCs arising within TEs in patients with presumed MFT were likely misdiagnosed cases of nevoid BCC. This report is a compelling example of MFT in which BCCs evolved secondarily. Awareness of the potential for the evolution of carcinoma in patients with MFT is important in the management of these patients. [ABSTRACT FROM AUTHOR]

Tuberculosis is a major cause of death worldwide. Understanding of the pathogenicity of Mycobacterium tuberculosis has been advanced by gene analysis and has led to the identification of genes that are important for intracellular survival in macrophages. One of these genes encodes HsaD, a meta-cleavage product (MCP) hydrolase that catalyzes the hydrolytic cleavage of a carbon--carbon bond in cholesterol metabolism. This paper describes the production of HsaD as a recombinant protein and, following crystallization, the determination of its three-dimensional structure to 2.35 Å resolution by X-ray crystallography at the Diamond Light Source in Oxfordshire, England. To the authors' knowledge, this study constitutes the first report of a structure determined at the new synchrotron facility. The volume of the active-site cleft of the HsaD enzyme is more than double the corresponding active-site volumes of related MCP hydrolases involved in the catabolism of aromatic compounds, consistent with the specificity of HsaD for steroids such as cholesterol. Knowledge of the structure of the enzyme facilitates the design of inhibitors. [ABSTRACT FROM AUTHOR]