The identification of tyrosine as a common key residue in unrelated H-2Kd restricted antigenic peptides.

We have compared the activity of several Kd- or Ld-restricted antigenic peptides as competitors in a functional competition assay using cytolytic T lymphocyte (CTL) clones. All of four unrelated Kd-restricted peptides tested could compete with each other but not with the Ld-restricted peptide P91A-. 12-24 (P91A). Moreover, the P91A peptide failed to compete with the four Kd-restricted peptides. In contrast, another Ld-restricted peptide [mouse cytomegalovirus (MCMV) pp89 167-176] could clearly compete with both Kd- and Ld-restricted peptides. The comparison of a series of modified MCMV pp89 peptides suggested that distinct structural features allow the interaction of the peptide with the two different MHC class I molecules. We showed previously that the competitor activity of two different Kd-restricted antigenic peptides was reduced substantially upon Ala substitution of the single Tyr residues present in these peptides. We now show a similar effect for two additional Kd-restricted peptides. Our results thus suggest that Tyr may function as an 'anchor' residue for many antigenic peptides that bind to the Kd molecule. Molecular modeling of the presumed antigen-binding site of the Kd molecule revealed the presence of two deep cavities that may be involved in binding peptide amino acid side chains. A model illustrating one possible interaction of a Tyr-containing peptide with the Kd molecule is presented.     

Pseudomembranous collagenous colitis with superimposed drug damage

Pseudomembranous collagenous colitis is a rare pathological condition, not related to infectious agents, and characterized by thickening of the subepithelial collagen and formation of pseudomembranes. We report one such case, which responded to budesonide treatment after failures of previous approaches given, being unaware of the correct diagnosis.     

Nodular extramedullary hematopoiesis involving the adrenal gland. An uncommon cause of adrenal "incidentaloma"

Adrenal extramedullary hematopoiesis may occur in association with various hematologic diseases. Its identification is invariably incidental, imaging of the lesion is poorly specific and the diagnosis requires the histological examination. We report a case of extramedullary hematopoiesis involving the right adrenal gland in a patient with hereditary spherocytosis. The literature on this entity has been reviewed and the differential with other conditions involving the adrenal gland and showing hematopoietic tissue infiltration is discussed.     

Spatial transfer of adaptation of scanning voluntary saccades in humans

The properties and neural substrates of the adaptive mechanisms that maintain over time the accuracy of voluntary, internally triggered saccades are still poorly understood. Here, we used transfer tests to evaluate the spatial properties of adaptation of scanning voluntary saccades. We found that an adaptive reduction of the size of a horizontal rightward 7 degrees saccade transferred to other saccades of a wide range of amplitudes and directions. This transfer decreased as tested saccades increasingly differed in amplitude or direction from the trained saccade, being null for vertical and leftward saccades. Voluntary saccade adaptation thus presents bounded, but large adaptation fields, suggesting that at least part of the underlying neural substrate encodes saccades as vectors.     

Assessing the impact of transcatheter aortic valve replacement on myocardial work indices and left ventricular diastolic function in aortic valve stenosis patients

Background

Aortic valve stenosis (AS) is the most common valvular heart disease worldwide. When timely intervention is performed, aortic valve replacement can improve patients' quality and duration of life. Load-independent left ventricular (LV) functional assessments, such as myocardial work indices (MWIs) and LV diastolic function parameters, could help clinicians decide on the optimal timing of intervention.

Aims

To evaluate the reliability of MWI in AS patients and the changes in MWI and LV diastolic function after transcatheter aortic valve replacement (TAVR).

Methods

We enrolled 53 consecutive patients with severe AS undergoing TAVR admitted between March 2021 and November 2021. MWIs and LV diastolic function were assessed before and after TAVR for each patient.

Results

All MWIs and LV diastolic function indices improved after TAVR. The degree of MWIs improvement was higher in patients with lower prior-TAVR MWI values, while the more severe the impairment of diastolic function, the greater the post-TAVR benefit.

Conclusion

The introduction of myocardial work parameters into the routine assessment of patients with AS could improve our understanding of cardiac performance and aid in identifying the optimal timing for surgical or percutaneous treatment.     

Somatotopy and temporal dynamics of sensorimotor interactions: evidence from double afferent inhibition

Moving and interacting with the world requires that the sensory and motor systems share information, but while some information about tactile events is preserved during sensorimotor transfer the spatial specificity of this information is unknown. Afferent inhibition (AI) studies, in which corticospinal excitability (CSE) is inhibited when a single tactile stimulus is presented before a transcranial magnetic stimulation pulse over the motor cortex, offer contradictory results regarding the sensory‐to‐motor transfer of spatial information. Here, we combined the techniques of AI and tactile repetition suppression (the decreased neurophysiological response following double stimulation of the same vs. different fingers) to investigate whether topographic information is preserved in the sensory‐to‐motor transfer in humans. We developed a double AI paradigm to examine both spatial (same vs. different finger) and temporal (short vs. long delay) aspects of sensorimotor interactions. Two consecutive electrocutaneous stimuli (separated by either 30 or 125 ms) were delivered to either the same or different fingers on the left hand (i.e. index finger stimulated twice or middle finger stimulated before index finger). Information about which fingers were stimulated was reflected in the size of the motor responses in a time‐constrained manner: CSE was modulated differently by same and different finger stimulation only when the two stimuli were separated by the short delay (P = 0.004). We demonstrate that the well‐known response of the somatosensory cortices following repetitive stimulation is mirrored in the motor cortex and that CSE is modulated as a function of the temporal and spatial relationship between afferent stimuli.     

Conformations of twisted parallel beta-sheets and the origin of chirality in protein structures.

An analysis of the conformational properties of parallel beta-pleated sheets suggests that an important factor in the generation of beta-sheet twist is the preference for nonplanar peptide bond distortions that impart local left-handed helical character to polypeptide chains. It is demonstrated that the introduction of such chiral distortions, which result from the tetrahedral deformation of the peptide nitrogen atoms, naturally produces right-twisted beta-sheet structures with optimal hydrogen bond geometry.