Hearing impairment is the most commonly occurring condition that affects the ability of humans to communicate. More than 50% of the cases of profound early-onset deafness are caused by genetic factors. Over 40 loci for non-syndromic deafness have been genetically mapped, and mutations in several genes have been shown to cause hearing loss. Mutations in the gene encoding connexin 26 (GJB2) cause both autosomal recessive and dominant forms of hearing impairment. To study the possible involvement of other members of the connexin family in hereditary hearing impairment, we cloned the gene (GJB3) encoding human gap junction protein beta-3 using homologous EST searching and nested PCR. GJB3 was mapped to human chromosome 1p33-p35. Mutation analysis revealed that a missense mutation and a nonsense mutation of GJB3 were associated with high-frequency hearing loss in two families. Moreover, expression of Gjb3 was identified in rat inner ear tissue by RT-PCR. These findings suggest that mutations in GJB3 may be responsible for bilateral high-frequency hearing impairment.

BackgroundLittle is known about the clinical features and treatment of Chinese patients with Parkinson disease (PD).MethodsA large cross-sectional survey of clinical features, medication use, and motor complications was conducted in 901 consecutive PD patients, from 42 randomly selected university-affiliated hospitals in four urban economic regions of China, between December 2006 and May 2007.ResultsThe 901 PD patients had age range 30 to 88, and median disease duration 50 months. Most (737, 81.8%) used L-dopa (median 375 mg/day), and often added low doses of other antiparkinsonian agents. Among L-dopa-treated patients, the prevalence of motor complications was low (dyskinesias: 8.5%; motor fluctuations: 18.6%), even among patients with disease duration ≥11 years (dyskinesias: 18.1%; motor fluctuations: 42.2%). Higher L-dopa use was associated with higher occurrence of dyskinesias (OR 2.44; 95% CI 1.20-5.13) and motor fluctuations (OR 2.48; 95% CI 1.49-4.14). Initiating PD treatment with L-dopa alone (OR 0.46; 95% CI 0.22-0.95) or in combination with other medications (OR 0.41; 95% CI 0.19-0.87) was associated with less dyskinesia than treatment initiated with non-L-dopa medication.ConclusionsMany Chinese PD patients are treated with low-dose L-dopa and added low-dose antiparkinsonian agents, with a low prevalence of motor complications, which might be influenced by Chinese culture.

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1 *04 subtypes best accounted for the association, strongest with HLA-DRB1 *04:04 and HLA-DRB1 *04:07, and intermediary with HLA-DRB1 *04:01 and HLA-DRB1 *04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1 *04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1 *04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.

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In order to study the characteristics of fine grained polycrystalline metals, it is important to recognize the function of grain boundaries (GB), crystal defects such as dislocation and/or nanoscale voids, since the fraction of GB increases as grain sizes decreases, the deformation process of these metals could be different from those in larger size grains. In this study, we first evaluate the hypothesis that GB behaves as dislocation source and sink during the deformation of fine grained metal, then compare the behavior between GB and a tiny defect from the view point of dislocation source and sink phenomena. Since continuous dislocation supplies could be considered as the key issue to improve the toughness of fine grained metals, this concept could be helpful to design next generation polycrystalline metals.