Dynamics of hydration water in deuterated purple membranes explored by neutron scattering

The function and dynamics of proteins depend on their direct environment, and much evidence has pointed to a strong coupling between water and protein motions. Recently however, neutron scattering measurements on deuterated and natural-abundance purple membrane (PM), hydrated in H2O and D2O, respectively, revealed that membrane and water motions on the ns–ps time scale are not directly coupled below 260 K (Wood et al. in Proc Natl Acad Sci USA 104:18049–18054, 2007). In the initial study, samples with a high level of hydration were measured. Here, we have measured the dynamics of PM and water separately, at a low-hydration level corresponding to the first layer of hydration water only. As in the case of the higher hydration samples previously studied, the dynamics of PM and water display different temperature dependencies, with a transition in the hydration water at 200 K not triggering a transition in the membrane at the same temperature. Furthermore, neutron diffraction experiments were carried out to monitor the lamellar spacing of a flash-cooled deuterated PM stack hydrated in H2O as a function of temperature. At 200 K, a sudden decrease in lamellar spacing indicated the onset of long-range translational water diffusion in the second hydration layer as has already been observed on flash-cooled natural-abundance PM stacks hydrated in D2O (Weik et al. in J Mol Biol 275:632–634, 2005), excluding thus a notable isotope effect. Our results reinforce the notion that membrane-protein dynamics may be less strongly coupled to hydration water motions than the dynamics of soluble proteins

Objectively measured early physical activity after total hip or knee arthroplasty

Although reduced early physical function after total hip- and knee arthroplasty (THA/TKA) is well-described, the underlying reasons have not been clarified with detailed studies on pathophysiological mechanisms related to recovery, thereby prohibiting advances in rehabilitation. Thus, we aimed to describe early post-THA/TKA physical activity measured by actigraphy and potential underlying pathophysiological mechanisms related to recovery in a well-defined cohort of THA and TKA patients. Daytime-activity was measured from 2 days before until 13 (THA) or 20 (TKA) days after surgery. The primary outcome was individualized recovery in activity, with secondary analyses of activity-intensities and association to the perioperative factors: sex, age, BMI, hemoglobin (hgb), C-reactive protein and postoperative pain. Eighty-one THA/TKA-patients were examined. A large inter-individual variation in early physical activity was found. On a group level, activity was significantly reduced compared to preoperatively the first 2 (THA) or 3 (TKA) weeks after surgery (mean-difference - 64 counts × 10 3/day, p &lt; 0.001 and - 78 counts × 10 3/day, p &lt; 0.001, respectively). All activity-intensities were affected with the largest decline in high intense activity. A slight overall improvement in activity was seen during the postoperative phase [THA: 1%/day (SD 2.15); TKA: 0.7%/day (SD 1.04)], but approximately 30% of THA and 20% of TKA patients had reduced and declining activity. Hgb, CRP, BMI (THA) and postoperative pain (TKA) were only weakly associated with impaired physical activity. Physical activity was reduced the first weeks following THA/TKA, but with large inter-individual variations in recovery profiles. No single pathogenic factor was associated with a poor recovery. Early risk stratified interventions are needed in patients on a suboptimal course. </p

Loss of function of the retinoid-related nuclear receptor (RORB) gene and epilepsy

Genetic generalized epilepsy (GGE), formerly known as idiopathic generalized epilepsy, is the most common form of epilepsy and is thought to have predominant genetic etiology. GGE are clinically characterized by absence, myoclonic, or generalized tonic-clonic seizures with electroencephalographic pattern of bilateral, synchronous, and symmetrical spike-and-wave discharges. Despite their strong heritability, the genetic basis of generalized epilepsies remains largely elusive. Nevertheless, recent advances in genetic technology have led to the identification of numerous genes and genomic defects in various types of epilepsies in the past few years. In the present study, we performed whole-exome sequencing in a family with GGE consistent with the diagnosis of eyelid myoclonia with absences. We found a nonsense variant (c.196C>T/p.(Arg66*)) in RORB, which encodes the beta retinoid-related orphan nuclear receptor (RORβ), in four affected family members. In addition, two de novo variants (c.218T>C/p.(Leu73Pro); c.1249_1251delACG/p.(Thr417del)) were identified in sporadic patients by trio-based exome sequencing. We also found two de novo deletions in patients with behavioral and cognitive impairment and epilepsy: a 52-kb microdeletion involving exons 5–10 of RORB and a larger 9q21-microdeletion. Furthermore, we identified a patient with intellectual disability and a balanced translocation where one breakpoint truncates RORB and refined the phenotype of a recently reported patient with RORB deletion. Our data support the role of RORB gene variants/CNVs in neurodevelopmental disorders including epilepsy, and especially in generalized epilepsies with predominant absence seizures