The problematic and numerous side effects of PUVA (psoralen and UVA) and other treatments currently in use for vitiligo, have justified the search for an alternative treatment. In this study, the use of khellin, a naturally occurring furochromone, which is similar in structure to psoralens, is explored as an alternative treatment for vitiligo. When khellin is combined with UVA (KUVA), it is reported to repigment vitiligo skin as effectively as PUVA photochemotherapy, but without the adverse effects reported with PUVA. The exact mechanism for khellin-induced repigmentation is still to be determined and no cell biological studies have yet been done to elucidate its mechanism of action. The specific aim of this project was to set up an in vitro tissue culture system to determine the direct effects of khellin, UVA and KUVA on melanocyte proliferation and pigmentation. Studies were carried out on cultures of a human melanoma cell line (Mel-1), normal human melanocytes and 3T3 mouse fibroblasts. Cell proliferation assays revealed that the proliferation of melanoma cells and melanocytes were increased after exposure to khellin for four days at concentrations ranging from 1nM to 0.5mM. A peak of proliferation was obtained at 0.01mM khellin, which stimulated proliferation of melanoma cells and melanocytes by 2.3 5-fold and 2.1- fold, respectively. In contrast, khellin decreased proliferation of fibroblasts over the entire concentration range tested. At concentrations of 0.5mM and above, khellin was cytotoxic to both melanocytic cells and fibroblasts. Cytotoxic assays revealed that 1mM khellin was equally cytotoxic to both melanoma cells and fibroblasts. In addition, these assays revealed that the proliferative response observed with 0.01mM and 0.1mM khellin, did not mask an underlying cytotoxic effect. Exposure to single doses of UVA between 150-280mJ/cm², increased proliferation of melanoma cells with maximal proliferation at 250mJ/cm², while the proliferation of normal melanocytes and fibroblasts were unaffected by this UVA dose. More significantly than khellin or UVA alone, the treatment with the combination of khellin and UVA (KUVA) stimulated proliferation of the melanocytic cells. The combination of 0.01mM khellin plus a single dose of UVA at 250mJ/cm² was the most effective treatment. KUVA combination treatments were found to be more cytotoxic to the fibroblasts than khellin or UVA alone. To test the effect of khellin, UVA and KUVA on melanogenesis, standard radiometric assays were carried out. The combination of khellin and UVA enhanced melanogenesis of the melanocytic cells more significantly than khellin alone or UVA alone. The dose of 0.01mM khellin plus 250mJ/cm² UVA (maximal proliferative dose) increased melanogenesis of the melanocytes by 290% above the untreated control melanocytes. To determine whether khellin and KUVA act by increasing levels of melanogenic proteins, western blot analyses were carried out. The results revealed that there were no differences in the amounts of TRP-2 and tyrosinase in the melanocytic cells treated with khellin alone. In contrast, those treated with KUVA (or UVA alone) had increased levels of the glycosylated form of the enzymes and also possibly had increased levels of the de nova form of the enzymes. These results suggest that UVA might be enhancing glycosylation of melanogenic enzymes and provides a novel insight into the possible mechanism for UVA-induced melanogenesis. The results also revealed that 3T3 fibroblasts expressed the non-glycosylated form of TRP-2, as described by others. In conclusion, this study suggests a model in which khellin acts directly on melanocytic cells by acting as a mitogen and a melanogen at non-toxic concentrations. Khellin possibly increases melanogenesis by acting post-translationally or antagonizing or removing an inhibitor of the melanogenic pathway. The melanocyte-specific effect of khellin and even more so KUVA, seems to suggest that khellin acts along the signal transduction pathways which increases both proliferation and melanogenesis in melanocytes, possibly via endothelin-1 pathways.

Infectious diseases, including helminthiases, are estimated to cause 16.1% of global cancer cases. While certain helminths are conclusive causes of cancer, others have been shown to reduce the disease. It is currently unknown why differing helminth infections promote or prevent cancer development and progression, or which cellular mechanisms are altered following exposure. Using several in vitro and in vivo techniques, this study aimed to determine the effect that certain helminths have on the progression of cervical and colorectal cancer. The results revealed that antigen from the hookworm Nippostrongylus brasiliensis significantly reduced cervical cancer cell migration and the expression of two markers of metastasis: vimentin and N-cadherin. Importantly, N. brasiliensis antigen significantly lowered the expression of cell-surface vimentin, while decreasing Human Papillomavirus type16 pseudovirion internalization. In vivo infection with N. brasiliensis significantly decreased vimentin expression within the female genital tract, confirming the relevance of these in vitro findings. Furthermore, exposure to antigen from the gastrointestinal nematode Heligmosomoides polygyrus decreased the in vitro proliferation of human and mouse colorectal cancer cells and simultaneously increased the expression of cell cycle regulator proteins, p53 and p21. Surprisingly, while antigen from H. polygyrus inhibited human colorectal cancer cell migration, it had the opposite effect on mouse colorectal cancer cells, suggesting that its impact on colorectal cancer migration may be, at the very least, species dependent. Using a syngeneic tumour model, the excretory-secretory product from H. polygyrus was shown to significantly increase tumour growth and the expansion of regulatory T cells and neutrophils in the tumour. Similarly, in a model of colitis-associated colorectal cancer this antigen significantly worsened pathology in a TGF-β dependent manner. Undoubtedly, the knowledge gained from this study will contribute to the limited understanding about helminths and the effect that these parasites have on cancer progression.

Includes bibliographical references. / Since the start of the HIV/AIDS pandemic in the 1980s, over 75 million individuals have been infected with the virus and it has been the cause of approximately 36 million deaths worldwide. With such a high morbidity and mortality in HIV-1 infected individuals, there is a need to find ways of controlling the disease. Development of an HIV-1 vaccine would help in the fight against HIV/AIDS. It is clear that other prevention strategies poorly reach vulnerable groups such as intravenous drug users and people living in war zones. More importantly, they generally provide very transient protection and do not provide the durable and affordable protection that could be expected from a vaccine. Antiretroviral therapy (ART) may be effective in reducing death and morbidity; but, treatment is life-long and ART is not a cure. However, producing immunogens that elicit neutralising antibodies that are protective against HIV-1 acquisition has proven difficult. This is not only because of the genetic diversity of the viruses circulating in the human population but is also as a result of an incomplete understanding of how to design effective immunogens based on the known targets for broadly neutralising antibodies (BnAbs). The availability of more potential targets for BnAbs is also an important goal. In this project, we designed a system to help identify novel targets of BnAbs if one or more does exist. We selected the QH343.A10 virus as the basis for this system. We found this virus to be moderately resistant to sera and resistant to all the BnAbs we initially tested against it (which target various epitopes on the HIV-1 envelope). QH343.A10 is resistant to monoclonal antibodies (mAbs) b12 (anti-CD4-binding site), 2G12 (anti-V3/glycan), 2F5 and 4E10 (both anti-membrane proximal external region). Of note, the virus is resistant to the extremely broad and potent mAb VRC01 (anti-CD4-bs). QH343.A10 was also found to be resistant to neutralisation by soluble CD4 (sCD4). This made the virus attractive to use in our system as antibodies that recognise QH343.A10 in the same manner as these mAbs are also unlikely to neutralise the virus. Therefore, we tested the ability of 474 serum samples, from ART-naïve chronically HIV-1-infected individuals from a Cape Town cohort, to neutralise QH343.A10. Sixty-six sera (14%) were able to neutralise the virus by an ID50 value of 150 or higher and were retained for further analysis. The sera which recognise the MPER, CD4-bs and V3/glycan regions in a similar way to the mAbs that are unable to neutralise QH343.A10 would presumably be similarly unable to neutralise the virus. Thus, just by identifying sera able to neutralise QH343.A10, we propose that we are already partially enriched against sera that recognise these three targets. Because we expected this enrichment to be only partially effective, we then systematically tested for and removed QH343.A10-recoginising sera that recognised the MPER, the V2/glycan-site and V3/glycan region. For technical reasons, we have not yet attempted to remove sera that recognise QH343.A10 through the CD4-binding site and CD4-inducible site (3BC176 mAb site), which are both targets for BnAbs. After exclusion of sera recognising the MPER, V2/glycan-site and V3/glycan region, we were left with 19 samples. We analysed neutralisation breadth and potency of these remaining 19 serum samples as we wanted to retain sera containing potent BnAbs. We remained with 12 sera samples which were broad and potent and did not detectably neutralise QH343.A10 through the MPER, V2/glycan -site or V3/glycan region. In this manner, we believe we have selected heavily for sera that could plausibly neutralise QH343.A10 through the recognition of a novel target of BnAbs. We propose that further study of this very select set of sera taken from a large serum cohort may allow identification of a novel target of broadly neutralising anti-HIV-1 antibodies, if such a target does exist. Our unique system can be used to screen a large panel of serum samples and allows the scientist to focus on those few samples that are broadly neutralising but do not detectably neutralise most of the already identified targets of broadly neutralising anti-HIV-1 antibodies.

Bacterial vaginosis (BV) and periodontal disease (PD) are conditions characterised by reduction of healthy bacterial communities in the vaginal and oral microbiomes respectively. Both BV and PD are associated with an increased risk of preterm labour and negative birth outcomes, yet it is unknown whether PD and BV are independent risk factors or may be interrelated. Understanding the health risks associated with pregnancies in young women is critical for developing new preventative interventions and for informing guidelines. Current knowledge of what constitutes a healthy microbiome is largely based on North American studies and may not be applicable to the South African population. This study characterises the oral and vaginal microbiome of South African female adolescents and investigates the association between alterations in oral bacterial diversity and BV in young South African women. DNA was extracted from matched lateral vaginal wall, saliva and periodontal samples and V4 16S sequencing was performed using MiSeq technology. The composition of the core oral microbiome of South African female adolescents was found to be similar to descriptive studies published in other populations. We additionally report a description the vaginal microbiome that is in agreement with previous studies in the South African population. PD-associated bacterial species were enriched in the oral microbiome of women with clinically diagnosed BV and in those with Lactobacillus iners dominant vaginal community types (VCTs) compared to asymptomatic women and those with L. crispatus dominated VCTs respectively. While this data provides evidence in support of a relationship between oral and vaginal dysbiosis, it unclear in which compartment bacterial dysbiosis would originate, should the association holds true.

Schistosomiasis is one of the most debilitating tropical diseases with the potential to cause morbidity and mortality in infected populations unless well controlled. Current control measures are limited to treatment with praziquantel. A rather alarming situation given i) the inability of the drug to directly target the pathogenic eggs, ii) the emergence of praziquantel-resistant schistosomes, iii) the persistence of tissue fibro-proliferative destruction caused by the trapped parasite eggs, even after treatment. Intestinal and liver immunopathology are pathognomonic of schistosomiasis and generally result from the host inadequate Th2 and or Th17 responses to the egg-derived antigens. Failure to control these immune responses causes the most of the detriment to the infected host, highlighting the need for a better understanding of the regulatory mechanisms which might help prevent excessive immune responsiveness and the ensuing immunopathology. A Basic leucine zipper transcription factor ATF-like 2 (BATF2) which belongs to a family of transcription factors critical in the control of inflammatory responses has gained enormous momentum recently as a potential target to immune deregulation during cancer and infectious diseases. We reasoned that an eventual BATF2 influence on the host immune response during schistosomiasis might unveil its anti-disease potency and greatly facilitate the quest for a novel control strategy against the immunopathology during schistosomiasis. Addressing this in our present study, BATF2-deficient mice were used and characterized for immunological and physiological parameters during steady state and Schistosomiasis. Although the liver showed a reduced pro-fibrotic response, there was a notable increase of several pro-fibrotic cytokines (TNF-α, IFN-ƴ, TGF-β and IL-13) Which further translated into an elevated level of granulomatous inflammation and fibrosis in the gut of S. mansoni infected BATF-2-deficient mice when compared to the liver tissues of BATF2-deficient mice and both livers and intestines of infected littermate controls indicating that BATF2 appears to have a tissue-specific role on the regulation of fibrogranulomatous inflammation during schistosomiasis. Therefore, BATF2 has a critical, and hitherto unappreciated, role in mediating the regulation of gut fibrogranulomatous response so as to promote host survival during schistosomiasis.

The aim of this project was to compare the breadth and magnitude of CFP10 and ESAT6-specific CD8 T cell responses in individuals with latent Mycobacterium tuberculosis (MTB) infection (LTBI) and active TB disease, and further define MTB-specific CD8 T cell phenotypes associated with latent infection and active disease. Ex vivo IFN? Elispots and proliferation assays were used to identify immunodominant ESAT6 and CFP10 15mer peptides targeted by CD8 T cells in LTBI and TB donors. A multiparameter flow cytometry panel was designed and optimized to assess turnover, susceptibility to apoptosis and terminal differentiation/senescence in CD8 T cells from TB and LTBI donors. Bcl-2, Ki67,CD95, CD57, CD127 and IFNγ were thus measured in each group.

Background: Tuberculosis (TB) remains a global health challenge and a quarter of the global population is infected with latent TB. It is a single infection that causes most deaths and was the number one cause of death in South Africa in 2017. Bacille Calmette-Guerin (BCG) remains the only licensed vaccine for protection against TB. Although TB primarily occurs as a pulmonary infection after inhalation of Mycobacterium tuberculosis (M. tuberculosis) bacilli, it can disseminate to other organs causing extra-pulmonary TB (EPTB). Approximately 5-15% of EPTB cases are attributed to central nervous system tuberculosis (CNS-TB) which commonly manifests as TB meningitis. CNS-TB is a severe form of TB associated with high morbidity and about 50% mortality due to inconclusive diagnosis and treatment challenges. Children and immunocompromised adults like those coinfected with HIV/AIDS are higher risk groups for the development of CNS-TB. Pathogenesis of CNS-TB occurs as a secondary infection during haematogenous dissemination of pulmonary TB to the brain parenchyma and meninges where inflammation occurs after rupture of rich foci into the subarachnoid space. Mechanisms by which M. tuberculosis infects the CNS and specific cell types targeted are not fully characterized. Little is understood of the cells that regulate CNS-TB, their respective functions, their cellular interactions, and contributions to the overall protection of the CNS. Most studies have focussed on microglia and macrophages as the preferential targeted antigen-presenting cells (APCs) by M. tuberculosis and neglected dendritic cells (DCs) to an extent because no consensus had been reached regarding the presence of DCs in a healthy CNS. Both myeloid (APCs) and T cells contribute to protection against CNS-TB. This study characterized the dendritic cell, microglial, macrophage, and T cell responses during mycobacterial infection of the CNS. We also investigated the modulation of T cells by DCs during CNS-TB. Methodology and Results: Wild-type female C57BL/6J mice were intracerebrally (i.c.) infected with M. tuberculosis H37Rv or Mycobacterium bovis BCG while control animals were saline inoculated and naive mice. Mice were euthanized at weeks 2, 4, 6, and organs harvested for experimental analysis. Histology results detected acid-fast bacilli using Ziehl-Neelsen (ZN) stain in the brains of M. tuberculosis and BCG i.c. infected mice, respectively. This was accompanied by a high degree of inflammatory responses in the brain ventricles and meninges of infected mice as compared to saline control mice shown by Hematoxylin and Eosin (H & E) staining. Although controlled brain bacterial burdens were demonstrated from homogenates of M. tuberculosis or BCG infected mice, dissemination to the spleen and lungs occurred. The histopathological results showed the successful reproduction of the murine CNS-TB infection model. For immunophenotyping, flow cytometry analysis of single-cell suspensions generated from brains and cervical lymph nodes were characterized for phenotypic and functional profiles. We detected the recruitment of macrophages and DCs to the brain from the periphery and an expansion of brain APCs (microglia, brain infiltrating macrophages, and DCs) during mycobacterial infection of the CNS. Brain APCs from infected animals displayed highly activated and mature phenotypes as shown by increased numbers of these cells expressing MHCII, co-stimulatory CD86 molecule, pro-inflammatory cytokines (IFNg, TNFa, IL-1b, IL-6, IL-12) and an anti-inflammatory cytokine (IL-10) in comparison to saline control mice. We also demonstrated preferential recruitment of mature conventional DCs (CD11c+, MHCII+) that express chemokine receptor-7 (CCR7) to the brain and cervical lymph nodes (CLNs), a phenomenon that may have contributed to the recruitment and expansion of predominantly effector CD4+ T cells than CD8+ T cells (CD44+CD62L-) to the brain and CLNs during mycobacterial infection of the CNS. Increased numbers of recruited CD4+ T cells and CD8+ T cells expressed T-bet [T-helper (Th1) transcription factor) in the brain and CLNs post-infection. At week 4 post intracerebral infection, increased numbers of these T cells expressed both T-bet and FoxP3 (regulatory transcription factor) during CNS-TB and identified a higher frequency of polyfunctional IFNg+TGF-b+CD4+ T cells than IFNg+TGF-b+IL-10+CD4+ T cells. M. tuberculosis-infected DCs from CLNs of CNS-TB mice were cocultured with naïve CD3+ T cells to generate a DC-T cell coculture, cells were sorted using fluorescence-activated cell sorting (FACS). DC-T cell coculture demonstrated increased percentage expression of IFNg, IL-4, IL-10 and TGF-b responses by CD4+ T cells and CD8+ T cells during CNS-TB. Our in vitro coculture findings validated in vivo findings of recruited brain CD4+ T cell cytokine responses that showed a combination of Th1 and regulatory T cell immune responses. Conclusion: We successfully reproduced the CNS-TB murine model, which proved valuable in studying immune responses. The functional mature phenotypes of detected brain APCs (microglia, brain infiltrating macrophages, DCs) suggest their capabilities of inducing antigen-specific T cell responses that contributed to initiating and mediating immunity during mycobacterial infection of the CNS. Our study findings suggest protection against mycobacterial infection of the CNS was achieved by characterized cells based on reduced brain bacterial burdens and 100% animal survival rate. Detrimental disease outcome was prevented by the balance achieved between proinflammatory and anti-inflammatory responses. The novel mechanism employed by conventional DCs during CNS-TB is modulating CD4+ and CD8+ T cell cytokine responses to Th1 and Treg polarization that achieved M. tuberculosis control in the brain. We demonstrated that DCs can be targeted for strategic therapeutic intervention against CNS-TB. Therefore; we support ongoing research that focuses on DCs for the development of tuberculosis vaccines and host-directed therapy. This study provided new knowledge on immune mechanisms and pathogenesis experienced during TBM, thus adding to the current gap of advancing basic and translational TBM research that will inform clinical interventions. These new insights have the potential to help reduce the high death and disability associated with CNS-TB.

Background: Platelets are small, anucleate cells which circulate in blood and are often the first to respond to tissue damage and vascular inflammation caused by pathogens. Here they not only maintain tissue integrity and prevent bleeding, but also initiate and regulate a vast variety of immunologic responses. Little is known on the role of platelets in helminth infections, despite our understanding that many helminth species cause significant vascular pathology as they transfer from the circulatory system to diverse tissues as part of their life cycles. Based on previous studies showing tight association between platelets and innate immune responses during infection with other pathogens, we hypothesized that platelets significantly contribute toward acute (vascular) immunity to helminth infection. Objectives: This project aimed to investigate the role of platelets in regulating acute innate immune responses following infection with the murine gastro-intestinal nematode N. brasiliensis (Nb), commonly used to model human helminthiases. Specifically, it aimed to characterized plateletregulated responses involved in acute innate immunity during the pulmonary stage of infection, in which larvae exit the pulmonary vasculature and invade host lung tissue. Methods: C57BL/6mice were infected with 500 L3 Nb larvae, and the association of platelets with acute innate immune responses in the circulation and the lung were established by flow cytometry and immunohistochemistry. In further experiments, mice were depleted of their platelets using antibodies prior to infection with Nb and the effect of this on pulmonary pathology and innate immune responses was inferred from flow cytometric and histologic analyses of pulmonary tissues. Lastly, antibodies were used to interfere with platelet receptors during Nb infection to gain mechanistic insight into platelet regulation of neutrophil responses. Results: Infection with N. brasiliensis was associated with significant changes in the activation of platelets, their localisation into lung tissue and their interaction with innate immune cells. Additionally, platelet -immune cell interaction was associated with changes in the expression of factors known to play a role in driving the early immune response to Nb, including IFN-γ and RELMα. Furthermore, mice depleted of their platelets prior to infection had significantly enhanced pulmonary pathology and rapidly succumbed to infection. This was associated with significant changes in neutrophil responses, and depletion of neutrophils together with platelets significantly protected against enhanced pathology. Finally, direct and indirect targeting of the platelet receptors CD62P and CLEC-2 did not result in significantly enhanced pulmonary pathology but was associated with altered platelet and neutrophil responses. Conclusion: Herein, we have provided evidence that platelets tightly associate with protective host responses during acute N. brasiliensis infection and that their absence correlates with a dysregulated neutrophil response and enhanced helminth – associated pulmonary pathology. These data therefore collectively show that platelets play notable roles in the acute innate immune response to N. brasiliensis and that future investigations into the immunological functioning of platelets during helminth infection are warranted.

Allergies are described as an unnecessary immune response to non-harmful substances known as allergens. Both allergic asthma and atopic dermatitis (AD) are said to be induced by elevated levels of immunoglobulin E (IgE) and T helper 2 (Th2) immune cells and inflammatory associated cells such as eosinophils, mast, and basophils. Globally, asthma is affecting more than 300 million people and is characterized by chronic airway inflammation, reversible airflow limitation, and airway hyperreactivity. AD is affecting approximately 15%-20% of the pediatric population and 7%-10% of adults in the world and is characterized by dysregulation of skin barrier and immunity, eczematous lesions, dry and itchy skin. Dysfunctional tolerogenic immune response to these innocuous allergens has been described as a leading cause of allergic disease pathogenesis. Interleukin-4 induced gene 1 (IL-4i1) is a secreted L-amino acid oxidase enzyme mainly expressed by antigen-presenting cells (APCs) and upon activation by IL-4 and CD40, can be induced in B lymphocytes. IL-4i1 converts phenylalanine into phenylpyruvate, ammonia, and hydrogen peroxide which can induce effector T cells suppression by inhibiting their activation, proliferation, and cytokine production while promoting a regulatory T cell (Tregs) arm. The contribution of IL-4i1 and its immunoregulatory potential has not yet been explored in allergic asthma and atopic dermatitis. Thus, we proposed to investigate the role of IL-4i1 during allergic asthma and atopic dermatitis using acute mouse models. Female mice of 8-12 weeks old either sufficient (IL-4i1+/+) or deficient of IL4i1 (IL-4i1-/- ) backcrossed to BALB/c genetic background were used in this study. For induction of allergic asthma, a high dose (100µg/per mouse) of house dust mite (HDM) was used in sensitizing mice intratracheally at day 0 and challenged at day 7 to 11 intranasally under anaesthesia. To assess the development of asthma features, we measured lung function on day 14 and collected blood for ELISAs, mediastinal lymph nodes, and lung tissues for FACS and RNA. For induction of AD, a skin irritant vitamin D3 analog (MC903) was used to topically sensitize shaved mice (IL-4i1+/+ or IL-4i1-/- ) for 9 consecutive days. We assessed disease score and skin inflammation at day 10 and collected blood, inguinal lymph nodes, and skin for ELISAs, FACS, RNA, and histology analysis. In both disease models, we saw a significant reduction in total IgE in IL-4i1- deficient mice compared to IL-4i1+/+ littermate controls. A significant upregulation of Th2 cytokines and increased eosinophilia was seen in IL-4i1 deficient mice in the allergic asthma model with no changes in airway hyperresponsiveness. In AD model, we observed a protective effect in the absence of IL-4i1, which was demonstrated by no changes in body weight a reduced skin epidermal thickness, and reduced systemic type 2 cytokines, TSLP, IL-5, and IL-13 producing CD8 T cells. Furthermore, type 2 alarmin, TSLP was reduced at disease site. These results suggest a dichotomy of IL4i1 in regulation of type 2 immune responses depending on disease site. This data further suggests that IL4i1 may be a potential target for therapy against these diseases. Studies are currently underway to understand how IL-4i1 is induced and how it regulates downstream effector molecules and how these target molecules can be inhibited.

Bakgrund.I logopedisk röstbehandling vid könsdysfori får personer hjälp med att hitta en röst som motsvarar deras könsidentitet. Akustiska egenskaper så som grundton, intonation, röststyrka, artikulation och resonans har visat sig påverka uppfattningen av könstillhörighet. Genom att anpassa dessa akustiska aspekter uppnås förändringar i rösten som oftast styrs i en feminiserande eller maskuliniserande riktning. Det finns personer med könsdysfori som önskar en mer könsneutral röst. Kunskap saknas om vilka akustiska egenskaper som utmärker röster som uppfattas otydligt feminint respektiveotydligt maskulint.Syfte. Studiens syfte var att undersöka vilka akustiska egenskaper som utmärker kvinnoröster som har skattats ungefär lika högt feminint som maskulint i lyssnarbedömning samt att jämföra dessa röster med kvinnoröster som skattats högt feminint och lågt maskulint. Studien avsåg också att undersöka mansröster som skattats ungefär lika högt maskulint som feminint i lyssnarbedömning och jämföra dessa röster med mansröster som skattats högt maskulint och lågt feminint.Metod. Studien omfattade 24 röster som valdes utgående från hur de hade uppfattats av lyssnare. Akustiska mått som undersöktes var max- och medelvärde för grundton, variation i grundton, formantfrekvenser, bandbredder för vokaler i betonade stavelser samt avstånd i F2 mellan /u/ och /i/ och /u/ och /a/. Resultat. Resultatet visade att uppfattningen av femininitet och maskulinitet är ett resultat av flera olika aspekter i rösten. Störst skillnader mellan kvinnorösterna som jämfördes och mansrösterna som jämfördes fanns i grundton, variation i grundton samt i avstånd i andra formantfrekvensen mellan /u/ och /i/. Slutsatser. Huruvida en röst uppfattas i grad av femininitet och maskulinitet är en kombination av flera olika akustiska aspekter. Kvinnoröster som i lyssnarbedömning uppfattas lägst feminint har lägre grundton, mindre variation i grundton, lägre formantfrekvenser samt ett mindre avstånd mellan /u/ och /i/ i F2 jämfört med kvinnoröster som uppfattas högt feminint. Mansröster som i lyssnarbedömning uppfattas som lägst maskulint visade högre värden i grundton, mer variation i grundton och ett större avstånd mellan /u/ och /i/ i F2 jämfört med mansröster som uppfattas högt maskulint.Nyckelord. Femininitet, maskulinitet, röst, könsdysfori, akustiska egenskaper / Uppfattningar av femininitet och maskulinitet i röster