Word-specific cortical activity as revealed by the mismatch negativity

Neurophysiological brain activity evoked by individual spoken words and pseudowords was recorded and the mismatch negativity (MMN), an automatic index of experience-dependent auditory memory traces, was calculated. Consistent with earlier reported results, the MMN response to word-final syllables was enhanced compared with that elicited by the same syllables placed in a pseudoword context. Here we now demonstrate that the enhancement of the MMN elicited by two individual words showed different scalp topographies. The early word-specific brain activity is consistent with the assumption that the memory traces activated by individual words are carried by large neuronal ensembles that differ in their distributions over the cortex. Current source estimates localized the between-word differences in the right hemisphere and in parieto-occipital left-hemispheric areas. The differential brain responses to individual words appeared as early as ∼100 ms after the recognition points of the words, suggesting that their specific memory traces become active almost immediately after the information in the acoustic input is sufficient for word identification.     

Chemically synthesized solid phase oligosaccharide probes for carbohydrate-binding receptors. Interactions of the E-, L- and P-selectins with sialyl-Le(x) and O-sulphated forms linked to biotin or to polyacrylamide

There is a growing interest in chemically defined oligosaccharide reagents for identifying proteins that bind carbohydrates and determining the specificities of carbohydrate-binding proteins. Here, we compare three sets of chemically synthesized commercially available oligosaccharide conjugates as immobilized probes, for the binding signals that they elicit with known carbohydrate-binding receptors of the immune system, the E-, P- and L-selectins. The first set of conjugates is of oligosaccharides linked to biotin via a nine-carbon spacer. The second and third sets are multivalent derivatives in which the oligosaccharides are linked, via a three-carbon spacer to poly[N-(2-hydroxyethyl)acrylamide] (PAA) or to biotinylated PAA with an average of 20% substitution of the hydroxyethyl-amide groups by carbohydrate. The conjugates were immobilized on streptavidin-coated microwells if biotinylated, otherwise by drying in uncoated wells. The most robust binding curves, overall, were with the biotinylated PAA derivatives of the ligands immobilized on streptavidin wells. These reagents have permitted a reevaluation of selectin binding signals elicited by sialyl-Lewis(x) (SLe(x)) analogues having sulphate at position 6 of the galactose (6'SuSLe(x)) or of the N-acetylglucosamine (6SuSLe(x)). The results clarify the role of 6SuSLe(x), rather then 6'SuSLe(x), as a ligand for the selectins.     

Content of Autoantibodies to Bradykinin and β-Amyloid1-42 as a Criterion for Biochemical Differences between Alzheimer's Dementias

We measured serum content of autoantibodies to -amyloid protein A_1-42, its neurotoxic fragment A_25-35, vasopressin, bradykinin, thrombin, antithrombin III, ₂-macroglobulin, and angiotensin II in patients with various forms of Alzheimer's dementias, including presenile and senile dementias of the Alzheimer type. The ratio of antibradykinin and anti-A_1-42 autoantibody contents differed by 39% in these patients. Our results can be used for the development of a new biochemical method for differential diagnostics of dementias of the Alzheimer type.     

New Calicivirus isolated from walrus

The nucleotide sequence and genome organization of a new member of Caliciviridae was determined. Cell culture inoculated with fecal matter from walrus was used to recover fragments of a new virus by Suppression Subtractive Hybridization (SSH). The isolate was identified as a member of the Vesivirus genus of Caliciviridae and designated the name Walrus Calicivirus (WCV). Sets of PCR primers spanning the entire putative genome were designed using known sequences of other vesiviruses. The assembled genome was 8289 nucleotides (nt) long and shared no more than 87% identity with sequences of the other members of the genus Vesivirus. The largest open reading frame (ORF1) between positions 4-5646 encoded a polyprotein. ORF2, found at position 5652-7778, encoded a putative capsid protein. ORF3 overlapped ORF2 and encoded a small basic protein. Comparative analysis of multiple caliciviral capsid proteins was performed to propose a uniform capsid structural organization for this viral family.     

On-line compensation for perturbations of a reaching movement is cerebellar dependent: support for the task dependency hypothesis

Although the cerebellum has been shown to be critical for the acquisition and retention of adaptive modifications in certain reflex behaviors, this structures role in the learning of motor skills required to execute complex voluntary goal-directed movements still is unclear. This study explores this issue by analyzing the effects of inactivating the interposed and dentate cerebellar nuclei on the adaptation required to compensate for an external elastic load applied during a reaching movement. We show that cats with these nuclei inactivated can adapt to predictable perturbations of the forelimb during a goal-directed reach by including a compensatory component in the motor plan prior to movement initiation. In contrast, when comparable compensatory modifications must be triggered on-line because the perturbations are applied in randomized trials (i.e., unpredictably), such adaptive responses cannot be executed or reacquired after the interposed and dentate nuclei are inactivated. These findings provide the first demonstration of the condition-dependent nature of the cerebellums contribution to the learning of a specific volitional task.     

Evolutionary Classification of Homeodomains

Purpose and Methods: We performed multiple comparisons between available amino acid (aa) sequences of homeodomain(HOM)-containing proteins from a wide spectrum of animals to create an evolutionary classification of the proteins. Results: Based on results of statistical and special computational analyses of over 500 homeodomain aa sequences (HOMs) a novel system of concepts describing complex structural correlations between homologous proteins is proposed. This system includes such notions as differentiated isofunctionality of aa, chemotype, stereotype, local functional motifs, gradual conservativeness of aa positions, and group-specific domain patterns, as well as major categories of the evolutionary classification of HOMs (Division, Type, Branch, Class, Family, Series, Variety, Sort). Using this approach, a complete structural systematics of HOMs belonging to proteomes of eukaryotic animals is proposed. Conclusions: The proposed structural classification of HOMs is in full agreement with the bulk of experimental data revealing complex functional similarities and differences among HOMs in terms of their expression patterns in developing embryos. It turn, this classification can provide answers regarding homology among homeodomains when experimental data are conflicting.     

Relevance of O-acetyl and phosphoglycerol groups for the antigenicity of Streptococcus pneumoniae serotype 18C capsular polysaccharide

Capsular polysaccharides are important virulence factors of Streptococcus pneumoniae. The polysaccharide has been used as a component of vaccines against pneumococcal diseases either as plain polysaccharide or better conjugated to a protein. The last one is the vaccine of choice to target child protection. The immune responses depend on several polysaccharide physicochemical properties that can be affected during either purification or modification in the case of conjugate vaccines. In serotype 18C, the repeating unit has a complex structure having a branched pentasaccharide with two apparently labile subtituents: glycerol-phosphate and O-acetyl group. The loss of these groups may potentially reduce the ability of the 18C polysaccharide to induce the desired immune response. Therefore, the relationship of both groups with the antigenicity and immunogenicity of 18C capsular polysaccharide is explored. It is shown that glycerol-phosphate must be preserved for conserving adequate antigenicity of the 18C capsular polysaccharide. At the same time, it was proved that O-acetyl groups do not play any role for the antigenicity and immunogenicity.     

Another (Internal) Epineurium: Beyond the Anatomical Barriers of Nerves

The epineurium has been accepted as the outer anatomical barrier of the peripheral nerves. Our objective was to characterize the microanatomy of the layers surrounding nerves using different tissue-specific staining methods. Two hundred forty-two cross sections of human sciatic and median nerves, and brachial plexuses of eight fresh unembalmed cadavers, were examined. The samples were fixed in formaldehyde solution and stained with hematoxylin–eosin, Masson's trichrome, or epithelial membrane antigen under standard conditions. Because epithelial membrane antigen only stains the perineurium, we demonstrated using hematoxylin–eosin and Masson's trichrome that there were different collagen layers inside and outside the nerves. All fascicles had a collagen layer that surrounded the perineurium and were in close contact with it, with no adipose tissue between them. Unlike the perineurium, this layer, an “internal epineurium,” contained no cells, and it surrounded one or a small group of fascicles. Bundling these fascicles or small groups of fascicles together was the true epineurium, and between the true and internal epineurium, we consistently found an adipose-containing compartment. More proximal to this, the tibial and common peroneal nerves were bundled together by another collagen layer, the circumneurium, which also had a fat-cell-containing compartment deep to it. There were scattered collagen fibers among the adipocytes. Using tissue-specific staining, we were able to demonstrate a collagen layer, the “internal epineurium.” Outside the nerves, we identified several fat-containing concentric compartments. Those compartments were limited by collagen fiber layers that were also similar to the epineurium. Clin. Anat. 33:199–206, 2020. © 2019 Wiley Periodicals, Inc.