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Galectin‐3 is a member of the lectin family encoded by the LGALS3 gene on chromosome 14. It is secreted by a wide range of immune cells and mammary tumor cells. Through its activity on the tumor microenvironment, in particular on tumor‐infiltrating leukocytes, galectin‐3 improves the proliferation, survival, and colonizing ability of mammary neoplastic cells. Consequently, galectin‐3 expression in the tumor microenvironment could worsen therapeutic outcomes of breast neoplasms and become a biomarker and a therapeutic target in combined immunotherapy in breast neoplasms. There is a limited amount of information that is available on galectin‐3 in breast cancer in Africa. In this review, we analyze how galectin‐3 influences the tumor microenvironment and its potential as a biomarker and therapeutic target in breast neoplasms. We aim to emphasize the significance of investigating galectin‐3 in breast neoplasms in Africa based on the results of studies conducted elsewhere. [ABSTRACT FROM AUTHOR]

Genome-wide association studies for severe malaria (SM) have identified 30 genetic variants mostly located in non-coding regions. Here, we aimed to identify potential causal genetic variants located in these loci and demonstrate their functional activity. We systematically investigated the regulatory effect of the SNPs in linkage disequilibrium (LD) with the malaria-associated genetic variants. Annotating and prioritizing genetic variants led to the identification of a regulatory region containing five ATP2B4 SNPs in LD with rs10900585. We found significant associations between SM and rs10900585 and our candidate SNPs (rs11240734, rs1541252, rs1541253, rs1541254, and rs1541255) in a Senegalese population. Then, we demonstrated that both individual SNPs and the combination of SNPs had regulatory effects. Moreover, CRISPR/Cas9-mediated deletion of this region decreased ATP2B4 transcript and protein levels and increased Ca2+ intracellular concentration in the K562 cell line. Our data demonstrate that severe malaria-associated genetic variants alter the expression of ATP2B4 encoding a plasma membrane calcium-transporting ATPase 4 (PMCA4) expressed on red blood cells. Altering the activity of this regulatory element affects the risk of SM, likely through calcium concentration effect on parasitaemia. [ABSTRACT FROM AUTHOR]

Simple Summary: The prevalence of GJB2-related (MIM: 121011) congenital non-syndromic hearing impairment (NSHI) accounts for close to 50% in populations of Asian and European ancestry. However, in sub-Saharan Africa, except for Ghana, previous data showed that the prevalence of GJB2-associated NSHI is close to zero. To investigate the contribution of GJB2 mutations in autosomal recessive NSHI in Senegal, we screened 129 affected and 143 unaffected individuals from 44 multiplex families, 9 sporadic cases, and 148 hearing controls with no personal or family history of hearing impairment, by targeted gene sequencing. We identified three pathogenic GJB2 variants in 34% (n = 15/44) of multiplex families, of which 80% (n = 12/15) were consanguineous. The most common variant, GJB2: c.94C>T: p.(Arg32Cys), accounted for 27.3% (n = 12/44) of familial cases. We also identified the previously reported "Ghanaian" founder variant, GJB2: c.427C>T: p.(Arg143Trp), in four multiplex Senegalese families. Relatively high allele frequencies of c.94C>T. and c.427C>T variants were observed among the screened hearing controls: 1% (n = 2/148 ∗ 2), and 2% (n = 4/148 ∗ 2), respectively. No GJB6-D13S18 deletion was identified in any of the hearing-impaired participants. The data suggest that GJB2: c.94C>T: p.(Arg32Cys) should be routinely tested in NSHI in Senegal. This study aimed to investigate GJB2 (MIM: 121011) and GJB6 (MIM: 604418) variants associated with familial non-syndromic hearing impairment (HI) in Senegal. We investigated a total of 129 affected and 143 unaffected individuals from 44 multiplex families by segregating autosomal recessive non-syndromic HI, 9 sporadic HI cases of putative genetic origin, and 148 control individuals without personal or family history of HI. The DNA samples were screened for GJB2 coding-region variants and GJB6-D3S1830 deletions. The mean age at the medical diagnosis of the affected individuals was 2.93 ± 2.53 years [range: 1–15 years]. Consanguinity was present in 40 out of 53 families (75.47%). Variants in GJB2 explained HI in 34.1% (n = 15/44) of multiplex families. A bi-allelic pathogenic variant, GJB2: c.94C>T: p.(Arg32Cys) accounted for 25% (n = 11/44 families) of familial cases, of which 80% (n = 12/15) were consanguineous. Interestingly, the previously reported "Ghanaian" founder variant, GJB2: c.427C>T: p.(Arg143Trp), accounted for 4.5% (n = 2/44 families) of the families investigated. Among the normal controls, the allele frequency of GJB2: c.94C>T and GJB2: c.427C>T was estimated at 1% (2/148 ∗ 2) and 2% (4/148 ∗ 2), respectively. No GJB6-D3S1830 deletion was identified in any of the HI patients. This is the first report of a genetic investigation of HI in Senegal, and suggests that GJB2: c.94C>T: p.(Arg32Cys) and GJB2: c.427C>T: p.(Arg143Trp) should be tested in clinical practice for congenital HI in Senegal. [ABSTRACT FROM AUTHOR]

Background. Host factors, including host genetic variation, have been shown to influence the outcome of Plasmodium falciparum infection. Genome-wide linkage studies have mapped mild malaria resistance genes on chromosome 6p21, whereas NCR3-412 polymorphism (rs2736191) lying within this region was found to be associated with mild malaria. Methods. Blood samples were taken from 188 Plasmodium falciparum malaria patients (76 mild malaria patients, 85 cerebral malaria patients, and 27 severe non-cerebral malaria patients). NCR3-412 (rs2736191) was analysed by sequencing, and haematological parameters were measured. Finally, their association with clinical phenotypes was assessed. Results. We evidenced an association of thrombocytopenia with both cerebral malaria and severe non-cerebral malaria, and of an association of high leukocyte count with cerebral malaria. Additionally, we found no association of NCR3-412 with either cerebral malaria, severe non-cerebral malaria, or severe malaria after grouping cerebral malaria and severe non-cerebral malaria patients. Conclusions. Our results suggest that NCR3 genetic variation has no effect, or only a small effect on the occurrence of severe malaria, although it has been strongly associated with mild malaria. We discuss the biological meaning of these results. Besides, we confirmed the association of thrombocytopenia and high leukocyte count with severe malaria phenotypes. [ABSTRACT FROM AUTHOR]

Pro-inflammatory cytokines induced by glycosylphosphatidylinositols (GPIs) of Plasmodium falciparum contribute to malaria pathogenesis and hence, the naturally acquired anti-GPI antibody thought to provide protection against severe malaria (SM) by neutralizing the stimulatory activity of GPIs. In previous studies, the anti-GPI antibody levels increased with age in parallel with the development of acquired immunity, and high levels of anti-GPI antibodies were associated with mild malaria (MM) cases. In the present study, the relationship between the levels of pro-inflammatory cytokines and anti-GPI IgG antibody responses, parasitemia, and the clinical outcomes were evaluated in SM and mild malaria (MM) patients. Sera from a total of 110 SM and 72 MM cases after excluding of ineligible patients were analyzed for the levels of anti-GPI antibodies, IgG subclasses, and cytokine responses by ELISA. While the total anti-GPI antibody levels were similar in overall SM and MM groups, they were significantly higher in surviving SM patients than in fatal SM cases. In the case of cytokines, the TNF-α and IL-6 levels were significantly higher in SM compared to MM, whereas the IL-10 levels were similar in both groups. The data presented here demonstrate that high levels of the circulatory pro-inflammatory, TNF-α, and IL-6, are indicators of malaria severity, whereas anti-inflammatory cytokine IL-10 level does not differentiate SM and MM cases. Further, among SM patients, relatively low levels of anti-GPI antibodies are indicators of fatal outcomes compared to survivors, suggesting that anti-GPI antibodies provide some level of protection against SM fatality. [ABSTRACT FROM AUTHOR]

The African Society of Human Genetics (AfSHG) was formed to provide a forum for human genetics and genomics scientists in Africa to interact, network, and collaborate. This is critical to facilitate development of solutions to the public health burden of many rare and common diseases across the continent. AfSHG fully supports the Black Lives Matter movement, which is dedicated to fighting racism and ensuring that society values the lives and humanity of Black people. The AfSHG would like to add its "voice" to the public outcry against racism sparked by George Floyd's death and to declare its commitment to ensuring that injustice and systematic racism, as well as abuse and exploitation of Africans and their biological material, are no longer tolerated. This is particularly relevant now as African genomic variation is poised to make significant contributions across several disciplines including ancestry, personalized medicine, and novel drug discovery. "Black Lives Matter and Black Research Matters" is AfSHG's call for the global community to support halting, and reversing, the perpetuation of exploitation of African people through neocolonial malpractices in genomic research. We also propose five key ways to curb racism in science, so that we can move forward together, with a common humanity, collectively embracing scientific endeavors.

Pro-inflammatory cytokines induced by glycosylphosphatidylinositols (GPIs) of Plasmodium falciparum contribute to malaria pathogenesis and hence, the naturally acquired anti-GPI antibody thought to provide protection against severe malaria (SM) by neutralizing the stimulatory activity of GPIs. In previous studies, the anti-GPI antibody levels increased with age in parallel with the development of acquired immunity, and high levels of anti-GPI antibodies were associated with mild malaria (MM) cases. In the present study, the relationship between the levels of pro-inflammatory cytokines and anti-GPI IgG antibody responses, parasitemia, and the clinical outcomes were evaluated in SM and mild malaria (MM) patients. Sera from a total of 110 SM and 72 MM cases after excluding of ineligible patients were analyzed for the levels of anti-GPI antibodies, IgG subclasses, and cytokine responses by ELISA. While the total anti-GPI antibody levels were similar in overall SM and MM groups, they were significantly higher in surviving SM patients than in fatal SM cases. In the case of cytokines, the TNF-α and IL-6 levels were significantly higher in SM compared to MM, whereas the IL-10 levels were similar in both groups. The data presented here demonstrate that high levels of the circulatory pro-inflammatory, TNF-α, and IL-6, are indicators of malaria severity, whereas anti-inflammatory cytokine IL-10 level does not differentiate SM and MM cases. Further, among SM patients, relatively low levels of anti-GPI antibodies are indicators of fatal outcomes compared to survivors, suggesting that anti-GPI antibodies provide some level of protection against SM fatality.