The Early Spatio-Temporal Correlates and Task Independence of Cerebral Voice Processing Studied with MEG

The selectivity of the ubiquitin–26 S proteasome system (UPS) for a particular substrate protein relies on the interaction between a ubiquitin-conjugating enzyme (E2, of which a cell contains relatively few) and a ubiquitin–protein ligase (E3, of which there are possibly hundreds). Post-translational modifications of the protein substrate, such as phosphorylation or hydroxylation, are often required prior to its selection. In this way, the precise spatio-temporal targeting and degradation of a given substrate can be achieved. The E3s are a large, diverse group of proteins, characterized by one of several defining motifs. These include a HECT (homologous to E6-associated protein C-terminus), RING (really interesting new gene) or U-box (a modified RING motif without the full complement of Zn2+-binding ligands) domain. Whereas HECT E3s have a direct role in catalysis during ubiquitination, RING and U-box E3s facilitate protein ubiquitination. These latter two E3 types act as adaptor-like molecules. They bring an E2 and a substrate into sufficiently close proximity to promote the substrate's ubiquitination. Although many RING-type E3s, such as MDM2 (murine double minute clone 2 oncoprotein) and c-Cbl, can apparently act alone, others are found as components of much larger multi-protein complexes, such as the anaphase-promoting complex. Taken together, these multifaceted properties and interactions enable E3s to provide a powerful, and specific, mechanism for protein clearance within all cells of eukaryotic organisms. The importance of E3s is highlighted by the number of normal cellular processes they regulate, and the number of diseases associated with their loss of function or inappropriate targeting.

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Elucidating cyclic AMP signaling in subcellular domains with optogenetic tools and fluorescent biosensors

Biochemical Society Transactions ◽

10.1042/bst20190246 ◽

2019 ◽

Vol 47 (6) ◽

pp. 1733-1747 ◽

Cited By ~ 3

Author(s):

Christina Klausen ◽

Fabian Kaiser ◽

Birthe Stüven ◽

Jan N. Hansen ◽

Dagmar Wachten

Keyword(s):

Cyclic Amp ◽

Adenosine Monophosphate ◽

Adenylyl Cyclases ◽

Temporal Precision ◽

Fluorescent Biosensors ◽

Subcellular Domains ◽

Spatio Temporal ◽

Hydrolysis Of ◽

Shed Light ◽

Cyclic Amp Signaling

The second messenger 3′,5′-cyclic nucleoside adenosine monophosphate (cAMP) plays a key role in signal transduction across prokaryotes and eukaryotes. Cyclic AMP signaling is compartmentalized into microdomains to fulfil specific functions. To define the function of cAMP within these microdomains, signaling needs to be analyzed with spatio-temporal precision. To this end, optogenetic approaches and genetically encoded fluorescent biosensors are particularly well suited. Synthesis and hydrolysis of cAMP can be directly manipulated by photoactivated adenylyl cyclases (PACs) and light-regulated phosphodiesterases (PDEs), respectively. In addition, many biosensors have been designed to spatially and temporarily resolve cAMP dynamics in the cell. This review provides an overview about optogenetic tools and biosensors to shed light on the subcellular organization of cAMP signaling.

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When Hearing Does Not Mean Understanding: On the Neural Processing of Syntactically Complex Sentences by Listeners With Hearing Loss

Journal of Speech Language and Hearing Research ◽

10.1044/2020_jslhr-20-00262 ◽

2021 ◽

pp. 1-13

Author(s):

Margreet Vogelzang ◽

Christiane M. Thiel ◽

Stephanie Rosemann ◽

Jochem W. Rieger ◽

Esther Ruigendijk

Keyword(s):

Hearing Loss ◽

Sentence Processing ◽

Secondary Task ◽

Sentence Comprehension ◽

Inferior Frontal Gyrus ◽

Normal Hearing ◽

Cognitive Demands ◽

Sentence Complexity ◽

Complex Sentences ◽

And Task

Purpose Adults with mild-to-moderate age-related hearing loss typically exhibit issues with speech understanding, but their processing of syntactically complex sentences is not well understood. We test the hypothesis that listeners with hearing loss' difficulties with comprehension and processing of syntactically complex sentences are due to the processing of degraded input interfering with the successful processing of complex sentences. Method We performed a neuroimaging study with a sentence comprehension task, varying sentence complexity (through subject–object order and verb–arguments order) and cognitive demands (presence or absence of a secondary task) within subjects. Groups of older subjects with hearing loss ( n = 20) and age-matched normal-hearing controls ( n = 20) were tested. Results The comprehension data show effects of syntactic complexity and hearing ability, with normal-hearing controls outperforming listeners with hearing loss, seemingly more so on syntactically complex sentences. The secondary task did not influence off-line comprehension. The imaging data show effects of group, sentence complexity, and task, with listeners with hearing loss showing decreased activation in typical speech processing areas, such as the inferior frontal gyrus and superior temporal gyrus. No interactions between group, sentence complexity, and task were found in the neuroimaging data. Conclusions The results suggest that listeners with hearing loss process speech differently from their normal-hearing peers, possibly due to the increased demands of processing degraded auditory input. Increased cognitive demands by means of a secondary visual shape processing task influence neural sentence processing, but no evidence was found that it does so in a different way for listeners with hearing loss and normal-hearing listeners.

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The Production of Gesture and Speech by People With Aphasia: Influence of Communicative Constraints

Journal of Speech Language and Hearing Research ◽

10.1044/2019_jslhr-l-19-0020 ◽

2019 ◽

Vol 62 (12) ◽

pp. 4417-4432 ◽

Cited By ~ 2

Author(s):

Carola de Beer ◽

Jan P. de Ruiter ◽

Martina Hielscher-Fastabend ◽

Katharina Hogrefe

Keyword(s):

Language Impairment ◽

Daily Living ◽

Linguistic Performance ◽

Task Effects ◽

Communicative Abilities ◽

Gesture Production ◽

And Task ◽

Group Effects

Purpose People with aphasia (PWA) use different kinds of gesture spontaneously when they communicate. Although there is evidence that the nature of the communicative task influences the linguistic performance of PWA, so far little is known about the influence of the communicative task on the production of gestures by PWA. We aimed to investigate the influence of varying communicative constraints on the production of gesture and spoken expression by PWA in comparison to persons without language impairment. Method Twenty-six PWA with varying aphasia severities and 26 control participants (CP) without language impairment participated in the study. Spoken expression and gesture production were investigated in 2 different tasks: (a) spontaneous conversation about topics of daily living and (b) a cartoon narration task, that is, retellings of short cartoon clips. The frequencies of words and gestures as well as of different gesture types produced by the participants were analyzed and tested for potential effects of group and task. Results Main results for task effects revealed that PWA and CP used more iconic gestures and pantomimes in the cartoon narration task than in spontaneous conversation. Metaphoric gestures, deictic gestures, number gestures, and emblems were more frequently used in spontaneous conversation than in cartoon narrations by both participant groups. Group effects show that, in both tasks, PWA's gesture-to-word ratios were higher than those for the CP. Furthermore, PWA produced more interactive gestures than the CP in both tasks, as well as more number gestures and pantomimes in spontaneous conversation. Conclusions The current results suggest that PWA use gestures to compensate for their verbal limitations under varying communicative constraints. The properties of the communicative task influence the use of different gesture types in people with and without aphasia. Thus, the influence of communicative constraints needs to be considered when assessing PWA's multimodal communicative abilities.

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