Project description:A promising approach to understanding the mechanistic basis of speech is to study disorders that affect speech without compromising other cognitive or motor functions. Stuttering, also known as stammering, has been linked to mutations in the lysosomal enzyme-targeting pathway, but how this remarkably specific speech deficit arises from mutations in a family of general "cellular housekeeping" genes is unknown. To address this question, we asked whether a missense mutation associated with human stuttering causes vocal or other abnormalities in mice. We compared vocalizations from mice engineered to carry a mutation in the Gnptab (N-acetylglucosamine-1-phosphotransferase subunits alpha/beta) gene with wild-type littermates. We found significant differences in the vocalizations of pups with the human Gnptab stuttering mutation compared to littermate controls. Specifically, we found that mice with the mutation emitted fewer vocalizations per unit time and had longer pauses between vocalizations and that the entropy of the temporal sequence was significantly reduced. Furthermore, Gnptab missense mice were similar to wild-type mice on an extensive battery of non-vocal behaviors. We then used the same language-agnostic metrics for auditory signal analysis of human speech. We analyzed speech from people who stutter with mutations in this pathway and compared it to control speech and found abnormalities similar to those found in the mouse vocalizations. These data show that mutations in the lysosomal enzyme-targeting pathway produce highly specific effects in mouse pup vocalizations and establish the mouse as an attractive model for studying this disorder.
Project description:Chronic levodopa treatment for Parkinson's disease often results in the development of abnormal involuntary movement, known as L-dopa-induced dyskinesia (LIDs). Studies suggest that LIDs may be associated with aberrant corticostriatal plasticity. Using in vivo extracellular recordings from identified Type I and Type II medium spiny striatal neurons, chronic L-dopa treatment was found to produce abnormal corticostriatal information processing. Specifically, after chronic L-dopa treatment in dopamine-depleted rats, there was a transition from a cortically evoked long-term depression (LTD) to a complementary but opposing form of plasticity, long-term potentiation, in Type II "indirect" pathway neurons. In contrast, LTD could still be induced in Type I neurons. Interestingly, the one parameter that correlated best with dyskinesias was the inability to de-depress established LTD in Type I medium spiny striatal neurons. Taken as a whole, we propose that the induction of LIDs is due, at least in part, to an aberrant induction of plasticity within the Type II indirect pathway neurons combined with an inability to de-depress established plastic responses in Type I neurons. Such information is critical for understanding the cellular mechanisms underlying one of the major caveats to L-dopa therapy.
Project description:There is a notable shift toward more repression and criminalization in sex work policies, in Europe and elsewhere. So-called neo-abolitionism reduces sex work to trafficking, with increased policing and persecution as a result. Punitive "demand reduction" strategies are progressively more popular. These developments call for a review of what we know about the effects of punishing and repressive regimes vis-à-vis sex work. From the evidence presented, sex work repression and criminalization are branded as "waterbed politics" that push and shove sex workers around with an overload of controls and regulations that in the end only make things worse. It is illustrated how criminalization and repression make it less likely that commercial sex is worker-controlled, non-abusive, and non-exploitative. Criminalization is seriously at odds with human rights and public health principles. It is concluded that sex work criminalization is barking up the wrong tree because it is fighting sex instead of crime and it is not offering any solution for the structural conditions that sex work (its ugly sides included) is rooted in. Sex work repression travels a dead-end street and holds no promises whatsoever for a better future. To fight poverty and gendered inequalities, the criminal justice system simply is not the right instrument. The reasons for the persistent stigma on sex work as well as for its present revival are considered.
Project description:OBJECTIVES:Several trials have been published examining the role of antibiotics in dog bite wound management. A meta-analysis of these suggests that there is very little benefit to routine antibiotic prescription in these patients. All papers however incorporated rigorous wound care regimens involving large volume irrigation. METHODS:The authors undertook a telephone survey to investigate wound care and prescribing practice in bite wound management in accident and emergency and minor injury units in the Yorkshire region. RESULTS:Twenty one departments were contacted. Only 10% of departments routinely irrigate these wounds. Antibiotics are prescribed routinely in 71%. CONCLUSIONS:Management of dog bite wounds would not seem to be evidence based in most departments in this sample.
Project description:IntroductionParkinson disease is associated with various nonmotor symptoms, including rare respiratory dysfunction events. However, patients with Parkinson disease often have comorbid medical problems, such as respiratory distress, and differentiating nonmotor symptoms can be difficult.Case presentationA 78-year-old male presented with repetitive shortness of breath. He was diagnosed with Parkinson disease and chronic obstructive pulmonary disease (COPD) several years prior. His symptoms were ambiguous between acute COPD exacerbation and levodopa-related nonmotor symptoms of Parkinson disease. To clarify the underlying cause, we performed the levodopa challenge test. After the patient complained of dyspnea following levodopa administration, levodopa-induced respiratory dysfunction was diagnosed. After adjusting antiparkinson medication, the patient's respiratory symptoms gradually improved.ConclusionRespiratory dysfunction as a nonmotor symptom of Parkinson disease can be caused by levodopa medication. To determine whether the symptoms are induced by levodopa, the levodopa challenge test may be useful in clarifying symptoms related to antiparkinson medication.
Project description:Homonyms are a critical test case for investigating how the brain resolves ambiguity in language and, more generally, how context influences semantic processing. Previous neuroimaging studies have associated processing of homonyms with greater engagement of regions involved in executive control of semantic processing. However, the precise role of these areas and the involvement of semantic representational regions in homonym comprehension remain elusive. We addressed this by combining univariate and multivariate fMRI analyses of homonym processing. We tested whether multi-voxel activation patterns could discriminate between presentations of the same homonym in different contexts (e.g., bark following tree vs. bark following dog). The ventral anterior temporal lobe, implicated in semantic representation but not previously in homonym comprehension, showed this meaning-specific coding, despite not showing increased mean activation for homonyms. Within inferior frontal gyrus (IFG), a key site for semantic control, there was a dissociation between pars orbitalis, which also showed meaning-specific coding, and pars triangularis, which discriminated more generally between semantically related and unrelated word pairs. IFG effects were goal-dependent, only occurring when the task required semantic decisions, in line with a top-down control function. Finally, posterior middle temporal cortex showed a hybrid pattern of responses, supporting the idea that it acts as an interface between semantic representations and the control system. The study provides new evidence for context-dependent coding in the semantic system and clarifies the role of control regions in processing ambiguity. It also highlights the importance of combining univariate and multivariate neuroimaging data to fully elucidate the role of a brain region in semantic cognition.
Project description:Research on infant vocal development has provided notable insights into vocal interaction with caregivers, elucidating growth in foundations for language through parental elicitation and reaction to vocalizations. A role for infant vocalizations produced endogenously, potentially providing raw material for interaction and a basis for growth in the vocal capacity itself, has received less attention. We report that in laboratory recordings of infants and their parents, the bulk of infant speech-like vocalizations, or "protophones", were directed toward no one and instead appeared to be generated endogenously, mostly in exploration of vocal abilities. The tendency to predominantly produce protophones without directing them to others occurred both during periods when parents were instructed to interact with their infants and during periods when parents were occupied with an interviewer, with the infants in the room. The results emphasize the infant as an agent in vocal learning, even when not interacting socially and suggest an enhanced perspective on foundations for vocal language.
Project description:Levodopa-induced dyskinesia (LID) is a persistent behavioral sensitization that develops after repeated levodopa (L-DOPA) exposure in Parkinson disease (PD) patients. we used reduced representation bisulfite sequencing to determine the methylation status of cytosines genome wide at base pair resolution following a parkinsonian-like lesion and LID development. Due to the enrichment of RRBS, we focused our analysis to cytosines in a CpG context and observed extensive locus-specific changes in DNA methylation, including a preponderance of demethylation, in the dorsal striatum following the development of dyskinetic behaviors in our animal model system. Changes in DNA methylation were concentrated in putative regulatory regions of many genes known to be aberrantly transcribed following L-DOPA exposure and enriched for genes relevant to mechanisms of synaptic plasticity. In the areas of the genome exhibiting the highest levels of effect, the magnitudes of change to methylation were strongly correlated with dyskinetic behaviors.
Project description:This study used LENA recording devices to capture infants' home language environments and examine how qualitative differences in adult responding to infant vocalizations related to infant vocabulary. Infant-directed speech and infant vocalizations were coded in samples taken from daylong home audio recordings of 13-month-old infants. Infant speech-related vocalizations were identified and coded as either canonical or non-canonical. Infant-directed adult speech was identified and classified into different pragmatic types. Multiple regressions examined the relation between adult responsiveness, imitating, recasting, and expanding and infant canonical and non-canonical vocalizations with caregiver-reported infant receptive and productive vocabulary. An interaction between adult like-sound responding (i.e., the total number of imitations, recasts, and expansions) and infant canonical vocalizations indicated that infants who produced more canonical vocalizations and received more adult like-sound responses had higher productive vocabularies. When sequences were analyzed, infant canonical vocalizations that preceded and followed adult recasts and expansions were positively associated with infant productive vocabulary. These findings provide insights into how infant-adult vocal exchanges are related to early vocabulary development.