Search Results (6)

Background/Objectives: Hearing aids can be used as a treatment for tinnitus. There are indications that this treatment is most effective when the tinnitus pitch falls in the frequency range of amplification of the hearing aid. Then, the hearing aid provides masking of the tinnitus. Alternatively, it has been suggested that a gap in the amplification around the tinnitus pitch would engage lateral inhibition and thereby reduce the tinnitus. Methods: To test these ideas, we conducted a randomized controlled trial. Patients were fitted with hearing aids using three different amplification schemes: (1) standard amplification according to the NAL-NL2 prescription procedure, (2) boosted amplification at the tinnitus frequency to enhance tinnitus masking, and (3) notch-filtered amplification at the tinnitus frequency to engage lateral inhibition and suppress tinnitus. The goal was to compare the boosted and notched amplification schemes to standard amplification. The primary outcome measure was tinnitus handicap as measured by the Tinnitus Functional Index (TFI). The trial was designed as a double-blind Latin square balanced crossover study. Eighteen tinnitus patients with moderate hearing loss were included. All of them were experienced hearing aid users. After two weeks of initial adaptation to the new hearing aids with standard settings, each setting was tried for four weeks. Results: There was an average reduction of 6.9 points on the TFI score after the adaptation phase, possibly due to a placebo effect. The TFI score did not differ significantly from the standard setting after using the notched or the boosted settings. Although notched amplification performed better than boosted amplification, this difference did not reach the clinical significance level. Regardless of the TFI outcomes, most participants had an individual preference for a particular setting. This preference was approximately uniformly distributed across the three amplification schemes. Conclusions: Notch-filtered and boosted amplification did not provide better tinnitus suppression than standard amplification. The individual preferences highlighted the importance of tailor-made approaches to hearing aid amplification in clinical practice. Further studies should explore the differences among patient’s tinnitus and their preference for a hearing aid setting. Full article

S355NL structural steel is extensively employed in bridges, ships, and power station equipment owing to its excellent tensile strength, weldability, and low-temperature toughness. However, pronounced fluctuations in its Charpy impact energy at low temperatures significantly compromise the reliability and service life of critical components. In this study, vacuum-induction-melted ingots of S355NL steel containing 0–0.086 wt.% rare earth cerium were prepared. The effects of Ce on microstructures, inclusions, and impact toughness were systematically investigated using optical microscopy (OM), scanning electron microscopy (SEM), electron backscatter diffraction (EBSD), and Charpy V-notch testing. The results indicate that appropriate Ce additions (0.0011–0.0049 wt.%) refine the average grain size from 5.27 μm to 4.88 μm, reduce the pearlite interlamellar spacing from 204 nm to 169 nm, and promote the transformation of large-size Al₂O₃-MnS composite inclusions into fine, spherical, Ce-rich oxysulfides. Charpy V-notch tests at –50 °C reveal that 0.0011 wt.% Ce enhances both longitudinal (269.7 J) and transverse (257.4 J) absorbed energies while minimizing anisotropy (E_t/E_l  =  1.01). Conversely, excessive Ce addition (0.086 wt.%) leads to coarse inclusions and deteriorates impact performance. These findings establish an optimal Ce window (0.0011–0.0049 wt.%) for microstructural and inclusion engineering to enhance the low-temperature impact toughness of S355NL steel. Full article

The origin and evolution of genes are central themes in evolutionary biology and genomics, shedding light on how molecular innovations shape biological complexity and adaptation. This review explores the principal mechanisms underlying gene emergence in eukaryotes, including gene duplication, de novo gene birth, horizontal gene transfer, viral gene domestication, and exon shuffling. We examine the population dynamics that govern the fixation of new genes, their functional integration, and the selective forces acting upon them—from purifying selection to adaptive innovation. Examples such as NOTCH2NL and SRGAP2C, which originated through recent segmental duplications followed by neofunctionalization, illustrate how duplicate-derived de novo genes can play a key role in human brain development. In addition, we highlight the emerging relevance of nuclear architecture in determining the evolutionary fate of new genes, offering a spatial dimension to gene innovation. We also discuss methodological approaches for detecting new genes and inferring selection, and finally, we highlight the emerging role of the human pangenome in revealing hidden gene diversity and its implications for evolutionary and biomedical research. Understanding gene innovation not only enhances our grasp of evolutionary processes but also informs clinical studies on disease susceptibility and human uniqueness. Full article

Pediatric high-grade glioma (pHGG) encompasses a wide range of gliomas with different genomic, epigenomic, and transcriptomic features. Almost 50% of pHGGs present a mutation in genes coding for histone 3, including the subtype harboring the H3.3-G34 mutation. In this context, histone mutations are frequently associated with mutations in TP53 and ATRX, along with PDGFRA and NOTCH2NL amplifications. Moreover, the H3.3-G34 histone mutation induces epigenetic changes in immune-related genes and exerts modulatory functions on the microenvironment. Also, the functionality of the blood–brain barrier (BBB) has an impact on treatment response. The prognosis remains poor with conventional treatments, thus eliciting the investigation of additional and alternative therapies. Promising molecular targets include PDGFRA amplification, BRAF mutation, EGFR amplification, NF1 loss, and IDH mutation. Considering that pHGGs harboring the H3.3-G34R mutation appear to be more susceptible to immunotherapies (ITs), different options have been recently explored, including immune checkpoint inhibitors, antibody mediated IT, and Car-T cells. This review aims to summarize the knowledge concerning cancer biology and cancer-immune cell interaction in this set of pediatric gliomas, with a focus on possible therapeutic options. Full article

In his influential book “Evolution by Gene Duplication”, Ohno postulated that frameshift mutation could lead to a new function after duplication, but frameshift mutation is generally thought to be deleterious, and thus drew little attention in functional innovation in duplicate evolution. To this end, we here report an exhaustive survey of the genomes of human, mouse, zebrafish, and fruit fly. We identified 80 duplicate genes that involved frameshift mutations after duplication. The frameshift mutation preferentially located close to the C-terminus in most cases (55/88), which indicated that a frameshift mutation that changed the reading frame in a small part at the end of a duplicate may likely have contributed to adaptive evolution (e.g., human genes NOTCH2NL and ARHGAP11B) otherwise too deleterious to survive. A few cases (11/80) involved multiple frameshift mutations, exhibiting various patterns of modifications of the reading frame. Functionality of duplicate genes involving frameshift mutations was confirmed by sequence characteristics and expression profile, suggesting a potential role of frameshift mutation in creating functional novelty. We thus showed that genomes have non-negligible numbers of genes that have experienced frameshift mutations following gene duplication. Our results demonstrated the potential importance of frameshift mutations in molecular evolution, as Ohno verbally argued 50 years ago. Full article

Over the past few years, human-specific genes have received increasing attention as potential major contributors responsible for the 3-fold difference in brain size between human and chimpanzee. Accordingly, mutations affecting these genes may lead to a reduction in human brain size and therefore, may cause or contribute to microcephaly. In this review, we will concentrate, within the brain, on the cerebral cortex, the seat of our higher cognitive abilities, and focus on the human-specific gene ARHGAP11B and on the gene family comprising the three human-specific genes NOTCH2NLA, -B, and -C. These genes are thought to have significantly contributed to the expansion of the cerebral cortex during human evolution. We will summarize the evolution of these genes, as well as their expression and functional role during human cortical development, and discuss their potential relevance for microcephaly. Furthermore, we will give an overview of other human-specific genes that are expressed during fetal human cortical development. We will discuss the potential involvement of these genes in microcephaly and how these genes could be studied functionally to identify a possible role in microcephaly. Full article