Search

The present systematic review examined imaging findings in the Auditory Neuropathy Spectrum Disorder (ANSD) population.

Background The present study compared the central auditory processing abilities using electrophysiological tests in children with non-syndromic cleft lip and palate (NSCLP) and their age-matched control group.Method Thirty children aged 7 to 15 years were recruited for the study. Participants were divided into 2 groups. The clinical group (children with NSCLP) comprised 15 children, while the control group (craniofacially typical peers) comprised 15 children with normal hearing sensitivity and auditory processing skills. Electrophysiological tests, including auditory brainstem responses (ABR), binaural interaction component (BIC) of ABR, auditory late latency responses (ALLR), and P300 were assessed.Results The results showed deviant responses in ABR, BIC, and ALLR in children with NSCLP compared to craniofacially typical counterparts. However, no significant difference was observed in P300 between the two groups.Conclusion Children with NSCLP may be at a higher risk of central auditory processing disorder due to their abnormal neural transmission in the auditory nervous system. Also, assessing auditory processing abilities in children with NSCLP should include electrophysiological tests in the test battery for additional information regarding neural transmission.

Background: Tinnitus is the perception of sound when there is no external sound stimulus. Individuals with tinnitus may have altered neurological system corresponding to the auditory pathway. Therefore, central auditory processing abilities, which rely on the central auditory pathway, may be affected. This study reviewed the published studies regarding the impact of tinnitus on central auditory processing abilities. Main text: A total of 3087 studies were identified, of which 18 fulfilled the eligibility criteria and were included in the review. The included studies scored good or fair in the quality assessment checklist. The review showed that individuals who had tinnitus with normal hearing sensitivity performed poorly on temporal resolution tests, speech perception in noise, localization, and auditory memory. However, temporal patterning and dichotic tests were not shown to be affected by tinnitus. Conclusion: The audiologists involved in tinnitus assessment are recommended to include central auditory processing tests in routine evaluation for the early diagnosis and intervention for subjects with tinnitus.

Survival of trophoblast cells in the low oxygen environment of human placentation requires metalloproteinase-mediated shedding of HBEGF and downstream signaling. A matrix metalloproteinase (MMP) antibody array and quantitative RT-PCR revealed upregulation of MMP2 post-transcriptionally in human first trimester HTR-8/SVneo trophoblast cells and placental villous explants exposed to 2% O2. Specific MMP inhibitors established the requirement for MMP2 in HBEGF shedding and upregulation. Because α-amanitin inhibited the upregulation of HBEGF, differentially expressed genes were identified by next-generation sequencing of RNA from trophoblast cells cultured at 2% O2for 0, 1, 2 and 4 h. Nine genes, all containing HIF-response elements, were upregulated at 1 h, but only HSPA6 (HSP70B’) remained elevated at 2–4 h. The HSP70 chaperone inhibitor VER 155008 blocked upregulation of both MMP2 and HBEGF at 2% O2, and increased apoptosis. However, both HBEGF upregulation and apoptosis were rescued by exogenous MMP2. Proximity ligation assays demonstrated interactions between HSP70 and MMP2, and between MMP2 and HBEGF, supporting the concept that MMP2-mediated shedding of HBEGF, initiated by HSP70, contributes to trophoblast survival at the low O2concentrations encountered during the first trimester, and is essential for successful pregnancy outcomes. Trophoblast survival during human placentation, when oxygenation is minimal, required HSP70 activity, which mediated MMP2 accumulation and the transactivation of anti-apoptotic ERBB signaling by HBEGF shedding.

ABSTRACTThe proper establishment and organogenesis of the placenta is crucial for intrauterine fetal growth and development. Endometrial invasion by the extravillous trophoblast cells, as well as formation of the syncytiotrophoblast (STB), are of vital importance for placental function. Trophoblast migration and invasion is often compared to tumor metastasis, which uses many of the same molecular mechanisms. However, unlike cancer cells, both initiation and the extent of trophoblast invasion are tightly regulated by feto-maternal cross-talk, which when perturbed, results in a wide range of abnormalities. Multiple factors control the trophoblast, including cytokines and hormones, which are subject to transcriptional regulatory networks. The relevance of epigenetics in transcriptional regulation of trophoblast differentiation and invasion, as well as in the onset of placenta-related pregnancy disorders, became recognized decades ago. Although, there has been tremendous progress in uncovering the molecular foundation of placental development, there is still much to be learned about the epigenetic machinery, and its role in trophoblast differentiation and invasion.This review will provide an overview of the epigenetic control of trophoblast differentiation and invasion. It will also highlight the major epigenetic mechanisms involved in pregnancy complications related to placental deficiencies.

ABSTRACTWe previously reported that Rv1860 protein from Mycobacterium tuberculosisstimulated CD4+and CD8+T cells secreting gamma interferon (IFN-?) in healthy purified protein derivative (PPD)-positive individuals and protected guinea pigs immunized with a DNA vaccine and a recombinant poxvirus expressing Rv1860 from a challenge with virulent M. tuberculosis. We now show Rv1860-specific polyfunctional T (PFT) cell responses in the blood of healthy latently M. tuberculosis-infected individuals dominated by CD8+T cells, using a panel of 32 overlapping peptides spanning the length of Rv1860. Multiple subsets of CD8+PFT cells were significantly more numerous in healthy latently infected volunteers (HV) than in tuberculosis (TB) patients (PAT). The responses of peripheral blood mononuclear cells (PBMC) from PAT to the peptides of Rv1860 were dominated by tumor necrosis factor alpha (TNF-a) and interleukin-10 (IL-10) secretions, the former coming predominantly from non-T cell sources. Notably, the pattern of the T cell response to Rv1860 was distinctly different from those of the widely studied M. tuberculosisantigens ESAT-6, CFP-10, Ag85A, and Ag85B, which elicited CD4+T cell-dominated responses as previously reported in other cohorts. We further identified a peptide spanning amino acids 21 to 39 of the Rv1860 protein with the potential to distinguish latent TB infection from disease due to its ability to stimulate differential cytokine signatures in HV and PAT. We suggest that a TB vaccine carrying these and other CD8+T-cell-stimulating antigens has the potential to prevent progression of latent M. tuberculosisinfection to TB disease.

Fetal trophoblast cells obtained noninvasively early in gestation provided fetal DNA for comprehensive targeted sequencing across the genome.

The epidermal growth factor (EGF) family member, heparin binding EGF-like growth factor (HBEGF), is present in the uterus at the time of embryo implantation and is expressed in invading trophoblast cells of the placenta indicating its central role in implantation and subsequent placentation. Previous work has demonstrated that HBEGF protein levels are dramatically upregulated in trophoblast cells cultured at low (2%) O2without a change in HBEGF mRNA. Therefore, it can be hypothesized that HBEGF is translationally regulated by O2in trophoblast cells where it prevents apoptosis during the first trimester when O2levels are ~2%. MicroRNAs (miRNAs) are small non-coding RNA species that primarily target the 3' untranslated region (3'UTR) of mRNA and regulate translation. They are transcribed as pri-miRNAs by RNA Polymerase II and are subsequently processed by nuclear proteins Drosha and DGCR8 into shorter pre-miRNA precursors. After export into the cytoplasm, pre-miRNAs are processed into their mature form. MicroRNAs specifically bind to target transcripts and, due to imperfect base pairing, can alter translation of mRNA. A miRNA-mediated mechanism could be responsible for the translational regulation of HBEGF by O2concentration. In this study the role of miRNA in regulating translation of HBEGF mRNA through its 3'UTR was investigated. The potential role of miRNA in the targeted regulation of HBEGF biosynthesis was examined by RNAi knockdown of the miRNA-processing protein, DGCR8, in HTR-8/SVneo human first trimester trophoblast cells by transfection of siRNA using siPORT NeoFX transfection agent. Western blots with antibody against DGCR8 and toxicity assays were used to optimize conditions. HBEGF quantified by ELISA did not increase when DGCR8 was knocked down at 20% O2, indicating that HBEGF expression was not repressed by miRNA. However, the upregulation of HBEGF at 2% O2was inhibited. A dual luciferase reporter construct (psiCHECK-2) containing the intact HBEGF 3'UTR or specific subregions was implemented to examine its translational regulatory potential. The intact 3'UTR reduced luciferase activity (p=0.008). However, the isolated 5' and 3' regions of the 3'UTR increased reporter activity by 4- to 5-fold (p<0.05) when the central domain was removed. These findings suggest that miRNAs alter interaction between inhibitory elements in the central domain of the 3'UTR and flanking elements to increase HBEGF translation. It is concluded that HBEGF is not transcriptionally regulated by O2in human trophoblast cells, but is translationally regulated through the interaction of miRNA with the HBEGF 3'UTR. Supported by the intramural research program of NICHD/NIH.