Argyrophilic grain disease differs from other tauopathies by lacking tau acetylation

Post-translational modifications play a key role in tau protein aggregation and related neurodegeneration. Because hyperphosphorylation alone does not necessarily cause tau aggregation, other post-translational modifications have been recently explored. Tau acetylation promotes aggregation and inhibits tau’s ability to stabilize microtubules. Recent studies have shown co-localization of acetylated and phosphorylated tau in AD and some 4R tauopathies. We developed a novel monoclonal antibody against acetylated tau at lysine residue 274, which recognizes both 3R and 4R tau, and used immunohistochemistry and immunofluorescence to probe 22 cases, including AD and another eight familial or sporadic tauopathies. Acetylated tau was identified in all tauopathies except argyrophilic grain disease (AGD). AGD is an age-associated, common but atypical 4R tauopathy, not always associated with clinical progression. Pathologically, AGD is characterized by neuropil grains, pre-neurofibrillary tangles, and oligodendroglial coiled bodies, all recognized by phospho-tau antibodies. The lack of acetylated tau in these inclusions suggests that AGD represents a distinctive tauopathy. Our data converge with previous findings to raise the hypothesis that AGD could play a protective role against the spread of AD-related tau pathology. Tau acetylation as a key modification for the propagation tau toxicity deserves further investigation.     

Predoctoral interns’ nondisclosure in supervision

Abstract

In interviews with 14 counseling center predoctoral interns regarding a significant nondisclosure in supervision, eight interns reported good supervisory relationships and six indicated that they experienced problematic supervisory relationships. Nondisclosures for the interns in good supervisory relationships related to personal reactions to clients, whereas nondisclosures for interns in problematic supervisory relationships related to global dissatisfaction with the supervisory relationship. In both groups, interns mentioned concerns about evaluation and negative feelings as typical reasons for nondisclosure. Additional reasons for nondisclosure for interns in problematic supervision were power dynamics, inhibiting demographic or cultural variables, and the supervisor's theoretical orientation. Both groups described negative effects of nondisclosure on themselves and their relationships with clients. Interns in problematic supervision also reported that nondisclosures had negative effects on the supervisory relationship.     

Stabbing energy and force required for pocket-knives to pierce ribs

Purpose

In addition to reconstructing the course of events, the medical examiner will often have to answer questions regarding the force necessary to inflict a certain injury in stabbing incidents. Several groups have examined the force needed to penetrate soft-tissue and clothing; however, no studies addressing the energy needed for penetrating ribs exist. Therefore, we decided to investigate this force on an animal model.

Method

Ribs from healthy, 8 to 10-month-old pigs were used as a substitute for human ribs. These ribs were then stabbed either transversely or longitudinally with two different pocket-knife blades, namely a Swiss Army pocket knife and a sturdier pocket knife (Classic Schnitzmesser, Herbertz Solingen) dropped from a drop-tower at defined heights and therefore defined energies.

Results

Longitudinally orientated stabs showed complete piercing of the ribs at approximately 11 Joules (J) or with a stabbing force in excess of 906 Newton (N) for both blade types. Transversely orientated stabs, however, displayed complete piercing between 11 and 16 J, or in excess of 1198 N, with the sturdy pocket knife tending to require a little more energy than the Swiss army pocket knife.

Conclusions

Young adult porcine ribs are completely pierced by pocket knife blades at energies between 11 and 16 J. Assuming the porcine ribs are comparable to those ribs of young adult humans, our results indicate that a complete penetration of the chest wall through the ribs by stabbing with a pocket knife is rather easily achieved.

     

An overview of the potential strategies for NK cell‐based immunotherapy for acute myeloid leukemia

Patients with acute myeloid leukemia (AML) have relatively low survival rates compared to patients with other pediatric cancers. Relapse is frequent with conventional treatment and is a major cause of morbidity and mortality. Natural killer (NK) cells offer an alternative approach to chemotherapy that combats relapse by substantially eradicating AML blasts. New methods for enhancing NK cell activation and expression of the activating ligand on target malignant cells will increase the likelihood of success with this approach. We review these latest discoveries in NK cell‐based therapy for AML and delineate recent advances in sensitizing AML cells to NK cell‐mediated immunosurveillance.     

Nonstructural proteins NS2-3 and NS4A of classical swine fever virus: essential features for infectious particle formation

The nonstructural protein NS2-3 of pestiviruses undergoes tightly regulated processing. For bovine viral diarrhea virus it was shown that uncleaved NS2-3 is required for infectious particle formation while cleaved NS3 is essential for genome replication. To further investigate the functions of NS2-3 and NS4A in the pestivirus life cycle, we established T7 RNA polymerase-dependent trans-complementation for p7-NS2-3-4A of classical swine fever virus (CSFV). Expression of NS2-3 and NS4A in trans restored the production of infectious particles from genomes lacking NS2-3 expression. Co-expression of cleaved NS4A was essential. None of the enzymatic activities harbored by NS2-3 were required for infectious particle formation. Importantly, expression of uncleavable NS2-3 together with NS4A rescued infectious particles from a genome lacking NS2, demonstrating that cleaved NS2 per se has no additional essential function. These data indicate that NS2-3 and NS3, each in association with NS4A, have independent functions in the CSFV life cycle.