Protein-based biomaterials are an important class of materials for applications in biotechnology and medicine. The exquisite control of their composition, stereochemistry, and chain length offers unique opportunities to engineer biofunctionality, biocompatibility, and biodegradability into these materials. Here, we report the synthesis of a thermally responsive peptide polymer-based hydrogel composed of a recombinant elastin-like polypeptide (ELP) that rapidly forms a reversibly cross-linked hydrogel by the formation of intermolecular disulfide cross-links. To do so, we designed and synthesized ELPs that incorporate periodic cysteine residues (cELPs), and show that cELPs are thermally responsive protein polymers that display rapid gelation under physiologically relevant, mild oxidative conditions. Gelation of cELPs, at concentrations as low as 2.5 wt%, occurs in ~2.5 min upon addition a low concentration of hydrogen peroxide (0.3 wt%). We show the utility of these hydrogels for the sustained release of a model protein in vitro, and demonstrate the ability of this injectable biomaterial to pervade tumors to maximize tumor coverage and retention time upon intratumoral injection. cELPs represent a new class of injectable reversibly cross-linked hydrogels with properties intermediate between ELP coacervates and chemically cross-linked ELP hydrogels that will find useful applications in drug delivery and tissue engineering.
hydrogel; thermally responsive material; cross-linking; drug delivery
Vibrio coralliilyticus is a Gram-negative bacterium found in seawater and is associated with diseased marine organisms. Strains of V. coralliilyticus have been shown to infect coral from multiple genera. We report the draft genome sequence of V. coralliilyticus strain OCN008, the third V. coralliilyticus genome to be sequenced.
Prescription medication costs increase financial burden, often leading individuals to engage in intentional nonadherence. Little is known about what specific medication cost-coping strategies individuals with arthritis employ.
The purposes of this study are (1) to identify characteristics of individuals with arthritis who self-report prescription medication cost-coping strategies and (2) to examine the association between medication cost-coping strategies and health status.
Seven hundred twenty-nine people self-reporting arthritis and prescription medication use completed a telephone survey. Adjusted regression models examined medication cost-coping strategies and five health status outcomes.
Participants reported engaging in cost-coping strategies due to medication costs. Those borrowing money had worse psychosocial health and greater disability; those with increasing credit card debt reported worse physical functioning, self-rated health, and greater helplessness. Medication underuse was associated with worse psychosocial health, greater disability, and depressive symptoms.
Individuals with arthritis use multiple strategies to cope with medication costs, and these strategies are associated with adverse physical and psychosocial health status.
Medication cost; Medication underuse; Coping strategies; Health status outcomes; Arthritis
Pollen flow from a 0.46 ha plot of genetically engineered (GE) Prunus domestica located in West Virginia, USA was evaluated from 2000–2010. Sentinel plum trees were planted at distances ranging from 132 to 854 m from the center of the GE orchard. Plots of mixed plum varieties and seedlings were located at 384, 484 and 998 m from the GE plot. Bee hives (Apis mellifera) were dispersed between the GE plum plot and the pollen flow monitoring sites. Pollen-mediated gene flow from out of the GE plum plot to non-GE plums under the study conditions was low, only occurring at all in 4 of 11 years and then in only 0.31% of the 12,116 seeds analyzed. When it occurred, gene flow, calculated as the number of GUS positive embryos/total embryos sampled, ranged from 0.215% at 132 m from the center of the GE plum plot (28 m from the nearest GE plum tree) to 0.033–0.017% at longer distances (384–998 m). Based on the percentage of GUS positive seeds per individual sampled tree the range was 0.4% to 12%. Within the GE field plot, gene flow ranged from 4.9 to 39%. Gene flow was related to distance and environmental conditions. A single year sample from a sentinel plot 132 m from the center of the GE plot accounted for 65% of the total 11-year gene flow. Spatial modeling indicated that gene flow dramatically decreased at distances over 400 m from the GE plot. Air temperature and rainfall were, respectively, positively and negatively correlated with gene flow, reflecting the effects of weather conditions on insect pollinator activity. Seed-mediated gene flow was not detected. These results support the feasibility of coexistence of GE and non-GE plum orchards.
This study examines whether substance using women exposed to a lifetime sexual trauma (n = 457) are distinguishable from substance using women exposed to non-sexual trauma (n = 275) in terms of demographics, psychopathology and high-risk sexual behaviors. Baseline data were collected from out-of-treatment substance using women enrolled in an HIV prevention study. Logistic regression analyses revealed that when demographics, psychopathology and lifetime indicators of sexual risk were assessed simultaneously, poor health, depression, antisocial personality disorder and lifetime sex-trading were associated with sexual trauma exposure. When these significant factors were controlled, the experience of sexual trauma predicted recent (past 4 month) high risk sexual behaviors such as higher than average sexual partners. Treatment efforts with women who have experienced a sexual trauma may be enhanced by the inclusion of assessments of physical and mental health needs as well as sexual risk awareness training.
Sexual trauma exposure; HIV-risk; Substance dependence
The development of a vaccine against cytomegalovirus (CMV) has been designated as a high priority and adolescent females are a likely target population for CMV vaccination. A self-administered, internet-based survey was developed using constructs from the Health Belief Model to identify factors that may be associated with parental acceptance of a CMV vaccine for their adolescent daughters. Data from 516 parents were analyzed, the majority of whom were female, white, and college educated. Parental acceptance of a CMV vaccine was generally high. Perceived benefits of vaccine were independently associated with vaccine acceptance while history of previous vaccine refusal, concerns about safety and cost of the vaccine were negatively associated. These findings provide initial data on factors that are likely to influence parental acceptance of a CMV vaccine for adolescent girls.
Acceptance; Cytomegalovirus; Adolescents; Parents
The morbidity and mortality from donation of a right hepatic lobe for living donor liver transplantation (LDLT) is an important issue for this procedure. We report the prevalence of severe psychiatric postoperative complications from the Adult-to-Adult Living Donor Liver Transplantation Cohort study (A2ALL), which was established to define the risks and benefits of LDLT for donors and recipients.
Severe psychiatric complications were evaluated in all donors from the A2ALL study who were evaluated between 1998 and February 2003.
Of the 392 donors, 16 (4.1%) had one or multiple psychiatric complications, including three severe psychiatric complications (suicide, accidental drug overdose, and suicide attempt).
Despite extensive preoperative screening, some donors experience severe psychiatric complications, including suicide, after liver donation. Psychiatric assessment and monitoring of liver donors may help to understand and prevent such tragic events.
Transplantation; Psychiatric; Morbidity; Liver
1. To test whether alteration of the vocal fold medial surface contour can improve phonation. 2. To demonstrate that implant material properties affect vibration even when implant is deep to the vocal fold lamina propria.
Induced phonation of excised human larynges.
Thirteen larynges were harvested within 24 hours post-mortem. Phonation threshold pressure (PTP) and flow (PTF) were measured before and after vocal fold injections using either calcium hydroxylapatite (CaHA) or hyaluronic acid (HA). Small-volume injections (median 0.0625 mL) were targeted to the infero-medial aspect of the thyroarytenoid (TA) muscle. Implant locations were assessed histologically.
The effect of implantation on PTP was material-dependent. CaHA tended to increase PTP, whereas HA tended to decrease PTP (Wilcoxon test P = 0.00013 for onset). In contrast, the effect of implantation on PTF was similar, with both materials tending to decrease PTF (P = 0.16 for onset). Histology confirmed implant presence in the inferior half of the vocal fold vertical thickness.
Taken together, these data suggested the implants may have altered the vocal fold medial surface contour, potentially resulting in a less convergent or more rectangular glottal geometry as a means to improve phonation. An implant with a closer viscoelastic match to vocal fold cover is desirable for this purpose, as material properties can affect vibration even when the implant is not placed within the lamina propria. This result is consistent with theoretical predictions and implies greater need for surgical precision in implant placement and care in material selection.
Vocal fold contour; phonation threshold pressure; phonation threshold flow; vocal fold injection; excised larynx
The purpose of this case series was to describe immediate changes to weight and lipid profiles after a 21-day Standard Process whole food supplement and dietary modification program.
Changes in weight and lipid profiles were measured for 7 participants (6 men and 1 woman) participating in a 21-day program. The dietary modifications throughout the Standard Process program were consumption of (1) unlimited fresh or frozen vegetables and fruits and preferably twice as many vegetables as fruits, (2) ½ to 1 cup of cooked lentils or brown rice each day, (3) 4 to 7 teaspoons of cold pressed oils per day, and (4) at least 64 oz of water a day. After day 10 of the program, participants were allowed to consume 1 to 2 servings of baked, broiled, or braised poultry or fish per day. Participants consumed a whey protein–based shake as meal replacement 2 times per day. Nutritional supplementation included a cleanse product on days 1 to 7, soluble fiber supplementation including oat bran concentrate and apple pectin on all days, and “green food” supplementation on days 8 to 21.
Weight loss ranged between 5.2 (2.4 kg) and 19.9 lb (9.0 kg) (average, 11.7 lb; 5.3 kg). Total cholesterol levels decreased with ranges between 11 and 77 mg/dL, and low-density lipoprotein cholesterol levels decreased in a range between 7 and 67 mg/dL.
After participating in a dietary program, the 7 participants demonstrated short-term weight loss and improvements in their lipid profiles.
Weight reduction programs; Overweight; Obesity
The synthesis of a 4-dibenzocyclooctynol (DIBO) functionalized polyethylene glycol (PEG) and fabrication of hydrogels via strain-promoted, metal-free, azide-alkyne cycloaddition is reported. The resulting hydrogel materials provide a versatile alternative in which to encapsulate cells that are sensitive to photochemical or chemical crosslinking mechanisms.
hydrogel; click chemistry; human mesenchymal stem cell; cycloaddition
When hospitalized older adults have impaired cognition, family members or other surrogates must communicate with clinicians to provide information and make medical decisions for the patient. The present study describes communication experiences of surrogates who recently made a major medical decision for a hospitalized older adult.
Semi-structured interviews about a recent hospitalization.
Two hospitals both affiliated with 1 large medical school: an urban, public hospital; and a university-affiliated tertiary referral hospital.
Surrogates were eligible if they had recently made a major medical decision for a hospitalized patient aged 65 or older and were available for an interview within 1 month (2-5 months if the patient died).
Interviews were audio-recorded, transcribed, and analyzed using methods of grounded theory.
We interviewed 35 surrogates. They were 80% female, 44% white and 56% African American. Three primary themes emerged. We found the Nature of Surrogate/Clinician Relationships was best characterized as a relationship with a “team” of clinicians rather than individual clinicians due to frequent staff changes and multiple clinicians. Surrogates reported their Communication Needs, including frequent communication, information, and emotional support. Surrogates valued communication from any member of the clinical team, including nurses, social workers, and physicians. Third, surrogates described Trust and Mistrust, which were formed largely through surrogates’ communication experiences.
In the hospital, surrogates form relationships with a “team” of clinicians rather than with individuals. Yet effective communication and expressions of emotional support frequently occur and are highly valued by surrogates. Future interventions should focus on meeting surrogates’ needs for frequent communication, high levels of information and emotional support.
Communication; Proxy; Physician-patient relations
The morphology of lesions in mouse models of osteoarthritis (OA) has not been comprehensively characterized, in part because current histological assessments of OA focus primarily on articular cartilage. In the present study, sections of murine stifle joints with naturally occurring (aged animals) and surgically induced (destabilized medial meniscus, DMM) OA were examined using a newly developed histological grading scheme that includes quantitative measurements and semiquantitative grades to evaluate multiple joint tissues.
The data collected was analyzed using Principal Components Analysis (PCA); factor scores for each joint were generated. Individual parameters and factor scores were compared between surgical groups and among age groups. For comparison, the original Mankin Histological-Histochemical Grading System (HHGS) also was applied.
Overall, lesions were most severe in the medial tibial plateaus. Significant changes in articular cartilage and neighboring bone were identified in surgically induced models and in naturally occurring disease. Mean factor scores provided a comprehensive evaluation of joint changes. An important new finding was that chondrocyte cell death within the articular cartilage was a commonly identified lesion and its extent significantly increased with age. While the Mankin HHGS detected significant overall differences in OA severity between surgical groups, it was not sensitive in detecting age related differences, nor did it provide information regarding changes in individual tissues.
These results demonstrate the utility of this newly developed murine OA grading scheme in identifying lesions in articular cartilage and in other joint tissues. Surgically induced changes were similar to those occurring naturally with aging.
osteoarthritis; histology; murine; morphometry
There is discrepancy in the literature regarding the degree to which old age affects muscle bioenergetics. These discrepancies are likely influenced by several factors, including variations in physical activity (PA) and differences in the muscle group investigated. To test the hypothesis that age may affect muscles differently, we quantified oxidative capacity of tibialis anterior (TA) and vastus lateralis (VL) muscles in healthy, relatively sedentary younger (8 YW, 8 YM; 21–35 years) and older (8 OW, 8 OM; 65–80 years) adults. To investigate the effect of physical activity on muscle oxidative capacity in older adults, we compared older sedentary women to older women with mild-to-moderate mobility impairment and lower physical activity (OIW, n = 7), and older sedentary men with older active male runners (OAM, n = 6). Oxidative capacity was measured in vivo as the rate constant, kPCr, of postcontraction phosphocreatine recovery, obtained by 31P magnetic resonance spectroscopy following maximal isometric contractions. While kPCr was higher in TA of older than activity-matched younger adults (28%; p = 0.03), older adults had lower kPCr in VL (23%; p = 0.04). In OIW compared with OW, kPCr was lower in VL (~45%; p = 0.01), but not different in TA. In contrast, OAM had higher kPCr than OM (p = 0.03) in both TA (41%) and VL (54%). In older adults, moderate-to-vigorous PA was positively associated with kPCr in VL (r = 0.65, p < 0.001) and TA (r = 0.41, p = 0.03). Collectively, these results indicate that age-related changes in oxidative capacity vary markedly between locomotory muscles, and that altered PA behavior may play a role in these changes.
skeletal muscle; bioenergetics; physical function; metabolism; aging; mitochondria
To determine whether shared epitope (SE)–containing HLA–DRB1 alleles are associated with rheumatoid arthritis (RA) in African Americans and whether their presence is associated with higher degrees of global (genome-wide) genetic admixture from the European population.
In this multicenter cohort study, African Americans with early RA and matched control subjects were analyzed. In addition to measurement of serum anti–cyclic citrullinated peptide (anti-CCP) antibodies and HLA–DRB1 genotyping, a panel of >1,200 ancestry-informative markers was analyzed in patients with RA and control subjects, to estimate the proportion of European ancestry.
The frequency of SE-containing HLA–DRB1 alleles was 25.2% in African American patients with RA versus 13.6% in control subjects (P = 0.00005). Of 321 patients with RA, 42.1% had at least 1 SE-containing allele, compared with 25.3% of 166 control subjects (P = 0.0004). The mean estimated percent European ancestry was associated with SE-containing HLA–DRB1 alleles in African Americans, regardless of disease status (RA or control). As reported in RA patients of European ancestry, there was a significant association of the SE with the presence of the anti-CCP antibody: 86 (48.9%) of 176 patients with anti-CCP antibody–positive RA had at least 1 SE allele, compared with 36 (32.7%) of 110 patients with anti-CCP antibody–negative RA (P = 0.01, by chi-square test).
HLA–DRB1 alleles containing the SE are strongly associated with susceptibility to RA in African Americans. The absolute contribution is less than that reported in RA among populations of European ancestry, in which ~50–70% of patients have at least 1 SE allele. As in Europeans with RA, the SE association was strongest in the subset of African American patients with anti-CCP antibodies. The finding of a higher degree of European ancestry among African Americans with SE alleles suggests that a genetic risk factor for RA was introduced into the African American population through admixture, thus making these individuals more susceptible to subsequent environmental or unknown factors that trigger the disease.
Immigrant adolescents are one of the fastest growing segments of our population, yet we know little about how schools prepare them for citizenship. Although prior research suggests that high school civics education, academic achievement, and a sense of connection increase political participation in early adulthood, we do not know if these processes apply to immigrant youth. Using longitudinal, nationally representative data from the Adolescent Health and Academic Achievement study (AHAA) and the National Longitudinal Study of Adolescent Health (Add Health), we employ multilevel models to investigate the effects of formal and informal school curricula on early adult voting and registration. We find that children of immigrant parents who take more high school social studies coursework have higher levels of reported voter registration and voting. In addition, attending a high school where students have a greater sense of connection or where parents have more education are important predictors of registration and voting, regardless of immigrant status.
The unregulated activity of inteins during expression and consequent side reactions during work-up limits their widespread use in biotechnology and chemical biology. Therefore, we exploited a mechanism-based approach to regulate intein autocatalysis for biotechnological application. The system, inspired by our previous structural studies, is based on reversible trapping of the intein’s catalytic cysteine residue through a disulfide bond. Using standard mutagenesis, the disulfide trap can be implemented to impart redox control over different inteins and for a variety of applications both in vitro and in Escherichia coli. Thereby, we first enhanced the output for bioconjugation in intein-mediated protein ligation, also referred to as expressed protein ligation, where precursor recovery and product yield were augmented fourfold to sixfold. Second, in bioseparation experiments, the redox trap boosted precursor recovery and product yield twofold. Finally, the disulfide-trap intein technology stimulated development of a novel bacterial redox sensor. This sensor reliably identified hyperoxic E. coli harboring mutations that disrupt the reductive pathways for thioredoxin and glutathione, against a background of wild-type cells.
redox regulation; expressed protein ligation; bioseparations; redox sensor
We examined whether a current major depressive episode (MDE) at baseline predicted crack use and arrests at follow-up among women enrolled in drug court.
Primary analyses used zero-inflated Poisson (ZIP) and zero-inflated negative binomial (ZINB) regression analyses to predict both yes/no and number of 1) days of crack use and 2) arrests at 4-month follow-up from current (30-day) MDE. Secondary analyses addressed risk conferred by current versus past MDE.
Participants were 261 women in drug court.
MDE was assessed using the Diagnostic Interview Schedule. Days using crack and number of arrests were assessed using the Washington University Risk Behavior Assessment for Women.
Having a current MDE predicted likelihood of crack use, but not days of crack use among those who used. Current MDE did not predict presence or number of arrests at the 4-month follow-up. Women with current MDE were more likely to be using crack at follow-up than were those with recent (31+ days to 12 months) but not current MDE (OR = 5.71); past MDE did not increase risk of crack use.
First, predictors of yes/no crack use and arrests were different from predictors of numbers of these behaviors, illustrating the importance of analyses that address both. Second, current (30-day) MDE, but not past MDE, increases risk of crack use among women in drug court, implying that MDE-related risk of crack use could be lessened by effective depression treatment.
fluorescent probes; protein engineering; enzyme catalysis; peptides
To examine children’s comprehension of verb phrase (VP) ellipsis constructions in light of their automatic, online structural processing abilities and conscious, metalinguistic reflective skill.
Forty-two children ages 5 through 12 years listened to VP ellipsis constructions involving the strict/sloppy ambiguity (e.g., “The janitor untangled himself from the rope and the fireman in the elementary school did too after the accident.”) in which the ellipsis phrase (“did too”) had 2 interpretations: (a) strict (“untangled the janitor”) and (b) sloppy (“untangled the fireman”). We examined these sentences at a normal speech rate with an online cross-modal picture priming task (n = 14) and an offline sentence–picture matching task (n = 11). Both tasks were also given with slowed speech input (n = 17).
Children showed priming for both the strict and sloppy interpretations at a normal speech rate but only for the strict interpretation with slowed input. Offline, children displayed an adultlike preference for the sloppy interpretation with normal-rate input but a divergent pattern with slowed speech.
Our results suggest that children and adults rely on a hybrid syntax-discourse model for the online comprehension and offline interpretation of VP ellipsis constructions. This model incorporates a temporally sensitive syntactic process of VP reconstruction (disrupted with slow input) and a temporally protracted discourse effect attributed to parallelism (preserved with slow input).
verb phrase ellipsis; anaphors; cross-modal priming; online; offline; language comprehension; speech rate
Congenital cytomegalovirus (CMV) is a leading cause of disability, including sensorineural hearing loss, developmental delay, and mental retardation. Although the seroprevalence of CMV and associated exposure and behavioral risk factors have been reported in adolescent females, limited data exists in males.
Serum was obtained from males (aged 12–17 years) from 6/2006 – 7/2007 in Cincinnati, OH, Galveston, TX, and Nashville, TN and tested for CMV IgG antibody using a commercial assay. Participants completed a computer assisted screening interview to assess seven risk categories.
A total of 397 adolescent males were screened and 165 (47%) were seropositive. African American race, older age, and exposure to children ≤3 years of age in the home were significant predictors of CMV infection in the univariate analysis. Hispanic ethnicity, group living situations, saliva sharing behaviors, and intimate sexual contact were not associated with CMV infection. However, among those with a history of sexual contact, the number of life time partners was associated with CMV. In the final multivariate model, CMV seroprevalence was significantly higher in African American subjects (OR 1.99 (95% CI [1.27, 2.95]) and subjects >14 years of age (OR 1.1 (95%CI [1.00, 1.28]. With each additional risk factor, males had a 1.6x increased risk of CMV.
This study indicates that CMV infections are common in adolescent males, increase with age, and are associated with African American race. Further study is needed to understand these risk factors in preparation for a CMV vaccine targeted at both adolescent males and females.
This study indicates CMV infections are common in adolescent males, increase with age, and are associated with African Americans. Further study is needed to understand these risk factors in preparation for a CMV vaccine targeted at adolescent males and females.
computer assisted screening interview (CASI); Cytomegalovirus (CMV); Confidence Intervals (CIs); Enzyme Linked Immunosorbent Assay (ELISA); Standard deviation (SD)
17β-estradiol (E2) plays important roles in functions of many tissues. E2 effects are mediated by estrogen receptor (ER) α and β. ERs regulate transcriptions through estrogen responsive element (ERE)-dependent and ERE-independent modes of action. ER binding to ERE constitutes the basis of the ERE-dependent pathway. Direct/indirect ER interactions with transcription complexes define the ERE-independent signaling. ERs share functional features. Ligand-bound ERs nevertheless induce distinct transcription profiles. Live cell imaging indicates a dynamic nature of gene expressions by highly mobile ERs. However, the relative contribution of ER mobility at the ERE-independent pathway to the overall kinetics of ER mobility remains undefined. We used fluorescent recovery after photo-bleaching (FRAP) approach to assess the ligand-mediated mobilities ERE binding-defective ERs, EREBD. The decrease in ERα mobility with E2 or the selective ER modulator 4-hydroxyl-tamoxifen (4HT) was largely due to the interaction of the receptor with ERE. Thus, ERα bound to E2 or 4HT mediates transcriptions from the ERE-independent pathway with remarkably fast kinetics that contributes fractionally to the overall motility of the receptor. The antagonist ICI 182,780 immobilized ERαs. The mobilities of ERβ and ERβEBD in the presence of ligands were indistinguishable kinetically. Thus, ERβ mobility is independent of the nature of ligands and the mode of interaction with target sites. Chimeric ERs indicated that the carboxyl-termini are critical regions for the subtype-specific mobility. Therefore, while ERs are highly mobile molecules interacting with target sites with fast kinetics, an indication of the hit-and-run model of transcription, they differ mechanistically to modulate transcriptions.
Ligand; Nuclear Mobility; FRAP; ERE Binding; Estrogen Receptor α; Estrogen Receptor β
The purpose of this study was to conduct a systematic review of the literature of cardiovascular factors pertaining to incident Alzheimer disease (AD).
A systematic literature review was conducted of all studies of cardiovascular risk factors for incident AD listed in PUBMED in English from 2000–2007. Risk factors included hypertension, diabetes, exercise, alcohol intake, smoking, B complex vitamins, homocysteine, stroke, atrial fibrillation, APOE, lipids, and diet. Inclusion criteria consisted of diagnoses of incident AD and longitudinal studies with cohorts of 500 or more.
Individual clinically defined risk factors such as hypertension and diabetes were not significantly associated with increased risk for AD. The strength of the association for hypertension could be considerably strengthened by changing criteria such as midlife measurements or using higher cutoffs for systolic blood pressure. APOE ε4 was the most consistent risk factor. Interactions between risk factors modify risk particularly for hypertension and diabetes. Interactions modifying risk were also found for exercise and physical function, APOE ε4, diabetes and cholesterol.
In this review the evidence that single clinically defined cardiovascular risk factors are significantly associated with incident Alzheimer disease is inconsistent at best. The strength of the association of cardiovascular risk factors and AD can be influenced greatly by changing the parameters of measurement of risk factors and by identifying interactions between the factors.
incident Alzheimer disease; cardiovascular risk factors; interactions
Innate immune cells respond to microbial invaders using pattern recognition receptors that detect conserved microbial patterns. Among the cellular processes stimulated downstream of pattern recognition machinery is the initiation of autophagy, which plays protective roles against intracellular microbes. We have shown recently that Dictyostelium discoideum, which takes up bacteria for nutritive purposes, may employ pattern recognition machinery to respond to bacterial prey, as D. discoideum cells upregulate bactericidal activity upon stimulation by lipopolysaccharide (LPS). Here we extend these findings, showing that LPS treatment leads to induction of autophagosomal maturation in cells responding to the bacteria Staphylococcus aureus. Cells treated with the autophagy-inducing drug rapamycin clear internalized bacteria at an accelerated rate, while LPS-enhanced clearance of bacteria is reduced in cells deficient for the autophagy-related genes atg1 and atg9. These findings link microbial pattern recognition with autophagy in the social amoeba D. discoideum.
Dictyostelium discoideum; autophagy; Staphylococcus aureus; innate immunity; LPS; pattern recognition; phagocytosis; lysosome
Osteoarthritis (OA) is one of the most frequently occurring musculoskeletal diseases, posing a significant public health problem due to its impact on pain and disability. Traditional risk factors fail to account for all of the risk observed for OA outcomes. In recent years, our view of disease causation has broadened to include health risks that are created by an individual’s socioeconomic circumstances. Early research into social determinants has focused on social position and explored factors related to the individual such as education, income and occupation. Results from these investigations suggest that low education attainment and nonprofessional occupation are associated with poorer arthritis outcomes. More recently, research has expanded to examine how one’s neighborhood socioeconomic environment may be relevant to OA outcomes. This narrative review proposes a framework to help guide our understanding of how social context may interact with pathophysiological processes and individual-level variables to influence health outcomes in those living with OA.
osteoarthritis; sociall determinant; socioeconomic status