Falcipain-2 and falcipain-3 are critical hemoglobinases of Plasmodium falciparum, the most virulent human malaria parasite. We have determined the 2.9 Å crystal structure of falcipain-2 in complex with the epoxysuccinate E64 and the 2.5 Å crystal structure of falcipain-3 in complex with the aldehyde leupeptin. These complexes represent the first crystal structures of plasmodial cysteine proteases with small molecule inhibitors and the first reported crystal structure of falcipain-3. Our structural analyses indicate that the relative shape and flexibility of the S2 pocket are affected by a number of discrete amino acid substitutions. The cumulative effect of subtle differences, including those at “gatekeeper” positions, may explain the observed kinetic differences between these two closely related enzymes.

Background Lung cancer morbidity and mortality may increase the risk for distress in couples facing this malignancy. Purpose We examined the prevalence of psychological and relationship distress in lung cancer patients and their spouses, predictors of psychological distress for both, and whether relationship satisfaction moderated the relation between patient and spouse distress. Methods Participants (169 patients and 167 spouses) completed questionnaires provided during clinic appointments at baseline (within one month of treatment initiation) and through the mail 3 and 6 months later. Analyses were from the baseline data. Results In total, 34.6% of patients and 36.4% of spouses reported psychological distress. Patient and spouse distress were correlated, depending on the symptom examined. Only 10.9% of patients and 14.1% of spouses reported distressed spousal relationships. Distress predictors for patients included less positive social interaction support, more behavioral disengagement and self-distraction coping, and the spouse reporting less use of humor for coping. Predictors for spouses included more behavioral disengagement and substance use coping, more blaming the patient for causing the cancer, and the patient using more behavioral disengagement coping. Relationship satisfaction moderated the association between each partner's distress. Conclusions Psychosocial counseling for lung cancer patients should include spouses and target decreasing individual distress and enhancing relationship satisfaction.

Each of the 30 human amyloid diseases is associated with the aggregation of a particular precursor protein into amyloid fibrils. In transthyretin amyloidosis (ATTR), mutant or wild-type forms of the serum carrier protein transthyretin (TTR), synthesized and secreted by the liver, convert to amyloid fibrils deposited in the heart and other organs. The current standard of care for hereditary ATTR is liver transplantation, which replaces the mutant gene with the wild-type gene. However, the procedure is often followed by cardiac deposition of wild-type TTR secreted by the new liver. Here we find that amyloid fibrils extracted from autopsied and explanted hearts of ATTR patients robustly seed wild-type TTR into amyloid fibrils in vitro. Cardiac-derived ATTR seeds can accelerate fibril formation of wild-type and monomeric TTR at acidic pH and under physiological conditions, respectively. We show that this seeding is inhibited by peptides designed to complement structures of TTR fibrils. These inhibitors cap fibril growth, suggesting an approach for halting progression of ATTR.

Dry regenerable sorbent technology is one of the emerging technologies as a cost-effective and energyefficient technology for CO 2 capture from flue gas. Six sodium-based dry regenerable sorbents were prepared by spray-drying techniques. Their physical properties and reactivities were tested to evaluate their applicability to a fluidized-bed or fast transport-bed CO 2 capture process. Each sorbents contained 20-50 wt% of Na 2 CO 3 or NaHCO 3 . All sorbents except for Sorb NX30 were insufficient with either attrition resistance or reactivity, or both properties. Sorb NX30 sorbent satisfied most of the physical requirements for a commercial fluidizedbed reactor process along with good chemical reactivity. Sorb NX30 sorbent had a spherical shape, an average size of 89 µm, a size distribution of 38-250 µm, and a bulk density of approximately 0.87 g/mL. The attrition index (AI) of Sorb NX30 reached below 5% compared to about 20% for commercial fluidized catalytic cracking (FCC) catalysts. CO 2 sorption capacity of Sorb NX30 was approximately 10 wt % (>80% sorbent utilization) in the simulated flue gas condition compared with 6 of 30 wt % MEA solution (33% sorbent utilization). All sorbents showed almost-complete regeneration at temperatures less than 120 °C.

ObjectivesTo test whether loneliness is associated with the risk of cognitive impairment up to 11 years later in a European sample of middle‐aged and older adults. The study examines whether this association is independent of measures of social isolation, depression, and other risk factors for cognitive impairment and dementia.MethodsParticipants (N = 14 114) from the Survey of Health, Ageing and Retirement in Europe (SHARE) answered a single item on loneliness at baseline and were assessed for cognitive impairment every 2‐to‐3 years for 11 years. Participants who scored at least 1.5 standard deviations below the age‐graded mean on both a memory recall task and verbal fluency task were classified as impaired. A three‐item measure of loneliness was available for a sample of respondents followed up to 4 years.ResultsFeeling lonely was associated with increased risk of incident cognitive impairment (HR = 1.31, 95%CI = 1.19‐1.44), after accounting for age, sex, education, and SHARE country strata. The association was robust but reduced in magnitude when controlling for clinical and behavioral risk factors, health‐related activity limitations, social isolation, social disengagement, and depressive symptoms. The association was not moderated by socio‐demographic factors and was also apparent when using the three‐item loneliness scale instead of the single‐item measure.ConclusionsThese findings expand the extant literature on loneliness and the risk of cognitive impairment in older adulthood. Loneliness is one modifiable factor that can be intervened prior to the development of severe impairment or dementia.

The combined use of two non-invasive serum biomarkers (APRI and FIB-4) could stratify HCC risk for chronic HBV-infected patients with LLV.

The tetrameric protein transthyretin is a transporter of retinol and thyroxine in blood, cerebrospinal fluid, and the eye, and is secreted by the liver, choroid plexus, and retinal epithelium, respectively. Systemic amyloid deposition of aggregated transthyretin causes hereditary and sporadic amyloidoses. A common treatment of patients with hereditary transthyretin amyloidosis is liver transplantation. However, this procedure, which replaces the patient's variant transthyretin with the WT protein, can fail to stop subsequent cardiac deposition, ultimately requiring heart transplantation. We recently showed that preformed amyloid fibrils present in the heart at the time of surgery can template or seed further amyloid aggregation of native transthyretin. Here we assess possible interventions to halt this seeding, using biochemical and EM assays. We found that chemical or mutational stabilization of the transthyretin tetramer does not hinder amyloid seeding. In contrast, binding of the peptide inhibitor TabFH2 to ex vivo fibrils efficiently inhibits amyloid seeding by impeding self-association of the amyloiddriving strands F and H in a tissue-independent manner. Our findings point to inhibition of amyloid seeding by peptide inhibitors as a potential therapeutic approach. Transthyretin amyloidosis (ATTR) 2 is a fatal disease caused by the abnormal aggregation of the protein transthyretin (TTR). TTR, a transporter of retinol and thyroxine in blood, cerebrospinal fluid, and the eye, is secreted by the liver, choroid plexus, and retinal epithelium, respectively. TTR amyloid

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