Witches Ways of Knowing: The Adult Learning Process in Joining Social Groups

This study explored what motivates adults to engage in learning that leads to membership in a marginalized social group and the nature of their learning process. By interviewing a sample of Wiccans, we discovered an intense internal motivation that endures over years and an integrated, holistic learning process

Perspective Transformation Over Time: A Two-year Follow-up Study of HIV-Positive Adults

This study investigated the stability of a perspective transformation over time. The findings confirmed that perspective transformations, at least in our sample, are irreversible; we also discovered that meaning schemes continue to change

Role of unfolded proteins in lung disease.

The lungs are exposed to a range of environmental toxins (including cigarette smoke, air pollution, asbestos) and pathogens (bacterial, viral and fungal), and most respiratory diseases are associated with local or systemic hypoxia. All of these adverse factors can trigger endoplasmic reticulum (ER) stress. The ER is a key intracellular site for synthesis of secretory and membrane proteins, regulating their folding, assembly into complexes, transport and degradation. Accumulation of misfolded proteins within the lumen results in ER stress, which activates the unfolded protein response (UPR). Effectors of the UPR temporarily reduce protein synthesis, while enhancing degradation of misfolded proteins and increasing the folding capacity of the ER. If successful, homeostasis is restored and protein synthesis resumes, but if ER stress persists, cell death pathways are activated. ER stress and the resulting UPR occur in a range of pulmonary insults and the outcome plays an important role in many respiratory diseases. The UPR is triggered in the airway of patients with several respiratory diseases and in corresponding experimental models. ER stress has been implicated in the initiation and progression of pulmonary fibrosis, and evidence is accumulating suggesting that ER stress occurs in obstructive lung diseases (particularly in asthma), in pulmonary infections (some viral infections and in the setting of the cystic fibrosis airway) and in lung cancer. While a number of small molecule inhibitors have been used to interrogate the role of the UPR in disease models, many of these tools have complex and off-target effects, hence additional evidence (eg, from genetic manipulation) may be required to support conclusions based on the impact of such pharmacological agents. Aberrant activation of the UPR may be linked to disease pathogenesis and progression, but at present, our understanding of the context-specific and disease-specific mechanisms linking these processes is incomplete. Despite this, the ability of the UPR to defend against ER stress and influence a range of respiratory diseases is becoming increasingly evident, and the UPR is therefore attracting attention as a prospective target for therapeutic intervention strategies

Robert James Baker (1942-2018), Obituary

First paragraph: On 30 March 2018, the science of mammalogy and the American Society of Mammalogists lost one of the most influential figures of the last half-century. Robert James Baker died quietly at his home in Lubbock, Texas (Fig. 1). He was born on 8 April 1942 to James Simeon Baker and Laura Cooper in Warren, Arkansas. His father was killed during World War II and his mother remarried, resulting in his growing up with six half-siblings. According to Robert’s autobiography in Going afield (330—number refers to specific publication in “Bibliography”), he spent a good deal of his youth with his grandparents on a 100-acre farm in the West Gulf Coastal Plain of southeastern Arkansas. He identified his maternal grandmother, “Grandma Rosie,” as his best friend and his greatest influence during these years. His marriage to Jean Joyner on 19 August 1961 ended in divorce in 1975, but the marriage resulted in a daughter, April Baker-Padilla, and two grandchildren, Jason Baker and Faith Padilla. Robert was married to his wife of 39 years, Laura Kyle (M.D.), on 28 May 1978 in Lubbock. Their son, Robert Kyle Baker, preceded his father in death, which was a tragedy from which neither Robert nor Laura ever completely recovered

Bitopic binding mode of an M1 muscarinic acetylcholine receptor agonist associated with adverse clinical trial outcomes

The realisation of the therapeutic potential of targeting the M1 muscarinic acetylcholine receptor (M1 mAChR) for the treatment of cognitive decline in Alzheimer's disease has prompted the discovery of M1 mAChR ligands showing efficacy in alleviating cognitive dysfunction in both rodents and humans. Among these is GSK1034702, described previously as a potent M1 receptor allosteric agonist, which showed pro-cognitive effects in rodents and improved immediate memory in a clinical nicotine withdrawal test but induced significant side-effects. Here we provide evidence using ligand binding, chemical biology and functional assays to establish that rather than the allosteric mechanism claimed, GSK1034702 interacts in a bitopic manner at the M1 mAChR such that it can concomitantly span both the orthosteric and an allosteric binding site. The bitopic nature of GSK1034702 together with the intrinsic agonist activity and a lack of muscarinic receptor subtype selectivity reported here, all likely contribute to the adverse effects of this molecule in clinical trials. We conclude that these properties, whilst imparting beneficial effects on learning and memory, are undesirable in a clinical candidate due to the likelihood of adverse side effects. Rather, our data supports the notion that "pure" positive allosteric modulators showing selectivity for the M1 mAChR with low levels of intrinsic activity would be preferable to provide clinical efficacy with low adverse responses

Seasonal Patterns in Stable Isotope and Fatty Acid Profiles of Southern Stingrays (Hypanus americana) at Stingray City Sandbar, Grand Cayman

Ecotourism opportunities in the marine environment often rely heavily on provisioning to ensure the viewing of cryptic species by the public. However, intentional feeding of wildlife can impact numerous aspects of an animals’ behavior and ecology. Southern stingrays (Hypanus americana) provisioned at Stingray City Sandbar (SCS) in Grand Cayman have altered diel activity patterns and decreased measures of health. This study looked at seasonal changes in stable isotope (SI) and fatty acid (FA) profiles of provisioned stingrays at SCS. Plasma δ15N was higher in male stingrays (11.86 ± 1.71‰) compared to females (10.70 ± 1.71‰). Lower values for δ15N in males and females were measured in October during low tourist season, suggesting stingrays may be forced to rely on native prey items to supplement the decreased amount of provisioned squid available during this time. Plasma FA profiles were significantly different between sexes and across sampling time points, with FAs 22:6n3, 16:0, 20:5n3, 18:1n3C, 18:0 and 18:1n9T contributing to dissimilarity scores between groups. Dietary FAs primarily contributed to differences between males and females lending further evidence to differences in foraging patterns at SCS, likely due to intraspecific competition. Further, canonical analysis of principal coordinates (CAP) analysis of FA profiles suggest similar diets during peak tourist season and differences in diet between males and females during the low season. This study demonstrates alterations in feeding ecology in stingrays at SCS which is of critical importance for effective management of the SCS aggregation

Probing Single- to Multi-Cell Level Charge Transport in Geobacter Sulfurreducens DL-1

Microbial fuel cells, in which living microorganisms convert chemical energy into electricity, represent a potentially sustainable energy technology for the future. Here we report the single-bacterium level current measurements of Geobacter sulfurreducens DL-1 to elucidate the fundamental limits and factors determining maximum power output from a microbial fuel cell. Quantized stepwise current outputs of 92(±33) and 196(±20) fA are generated from microelectrode arrays confined in isolated wells. Simultaneous cell imaging/tracking and current recording reveals that the current steps are directly correlated with the contact of one or two cells with the electrodes. This work establishes the amount of current generated by an individual Geobacter cell in the absence of a biofilm and highlights the potential upper limit of microbial fuel cell performance for Geobacter in thin biofilms.Chemistry and Chemical Biolog

Emergency department-based peer support for opioid use disorder: Emergent functions and forms

Emergency department (ED)-based peer support programs aimed at linking persons with opioid use disorder (OUD) to medication for addiction treatment and other recovery services are a promising approach to addressing the opioid crisis. This brief report draws on experiences from three states' experience with such programs funded by the SAMHSA Opioid State Targeted Repose (STR) grants. Core functions of such programs include: Integration of peer supports in EDs; Alerting peers of eligible patients and making the patient aware of peer services; and connecting patients with recovery services. Qualitative data were analyzed using a general inductive approach conducted in 3 steps in order to identify forms utilized to fulfill these functions. Peer integration differed in terms of peer's physical location and who hired and supervised peers. Peers often depend on ED staff to alert them to potential patients while people other than the peers often first introduce potential patients to programming. Programs generally schedule initial appointments for recovery services for patients, but some programs provide a range of other services aimed at supporting participation in recovery services. Future effectiveness evaluations of ED-based peer support programs for OUD should consistently report on forms used to fulfill core functions

Predictors for mortality and loss to follow-up among children receiving anti-retroviral therapy in Lilongwe, Malawi

To determine predictors of mortality in children on anti-retroviral therapy (ART) who attended the Paediatric HIV Clinic at Kamuzu Central Hospital in Lilongwe, Malawi