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COVID-19 vaccination strategies, including heterologous prime–boost regimens and additional booster doses, aim to optimize immune responses. However, seroepidemiological studies on immune responses to different COVID-19 vaccine types and schedules remain limited. This study investigated antibody levels following homologous and heterologous prime-and-boost COVID-19 vaccination in Bangladesh. In a cohort of 606 participants who received first/second/booster doses of vaccines (AstraZeneca, Moderna, Pfizer-BioNTech, and Sinopharm), anti-spike IgG and anti-nucleocapsid IgG levels were measured. Antibody titer variations with respect to age, gender, intervals between doses, and prior infection status were analyzed. mRNA vaccines elicited the highest antibody levels after homologous and heterologous boosting. The AstraZeneca booster resulted in a sharp titer decline rate of ~0.04 units per day. Second or booster vaccine doses significantly increased antibody levels, especially in males (p < 0.05). Older age correlated with higher titers, likely reflecting previous infection, which was further confirmed by the elevation of anti-nucleocapsid IgG levels. About 95.5% of non-Sinopharm recipients were anti-nucleocapsid IgG positive, suggesting prior exposure exceeding self-reported infections (12.5%). mRNA and heterologous COVID-19 boosting enhances humoral immunity over homologous prime–boost vector/inactivated vaccination. However, waning immunity merits further investigation across vaccine platforms. [ABSTRACT FROM AUTHOR]

The kidney of marine teleosts is the major site of Mg2+ excretion and produces urine with a high Mg2+ concentration. However, the transporters involved in Mg2+ excretion are poorly understood. The cyclin M (Cnnm; also known as ancient conserved domain protein) family comprises membrane proteins homologous to the bacterial Mg2+ and Co2+ efflux protein, CorC. To understand the molecular mechanism of Mg2+ homeostasis in marine teleosts, we analyzed the expression of the Cnnm family genes in the seawater (SW) pufferfish, torafugu (Takifugu rubripes), and the closely related euryhaline species, mefugu (Takifugu obscurus). Database mining and phylogenetic analysis indicated that the Takifugu genome contains six members of the Cnnm family: two orthologs of Cnnm1, one of Cnnm2, one of Cnnm3, and two of Cnnm4. RT-PCR analyses indicated that Cnnm2, Cnnm3, and Cnnm4a are expressed in the kidney, whereas other members are mainly expressed in the brain. Renal expression of Cnnm3 was upregulated in SW mefugu, whereas renal expression of Cnnm2 was upregulated in freshwater (FW) mefugu. No significant difference was observed in renal expression of Cnnm4a between SW and FW mefugu. In situ hybridization and immunohistochemical analyses of the SW mefugu kidney revealed that Cnnm3 is expressed in the proximal tubule, and its product localizes to the lateral membrane. When Cnnm3 was expressed in Xenopus laevis oocytes, whole cellular Mg2+ content and free intracellular Mg2+ activity significantly decreased. These results suggest that Cnnm3 is involved in body fluid Mg2+ homeostasis in marine teleosts. [ABSTRACT FROM AUTHOR]

The second most abundant cation in seawater (SW), Mg2+, is present at concentrations of ~53 mM. Marine teleosts maintain plasma Mg2+ concentration at 1-2 mM by excreting Mg2+ into the urine. Urine Mg2+ concentrations of SW teleosts exceed 70 mM, most of which is secreted by the renal tubular epithelial cells. However, molecular mechanisms of the Mg2+ secretion have yet to be clarified. To identify transporters involved in Mg2+ secretion, we analyzed the expression of fish homologs of the Slc41 Mg2+ transporter family in various tissues of SW pufferfish torafugu (Takifugu rubripes) and its closely related euryhaline species mefugu (Takifugu obscurus). Takifugu genome contained five members of Slc41 genes, and only Slc41a1 was highly expressed in the kidney. Renal expression of Slc41a1 was markedly elevated when mefugu were transferred from fresh water (FW) to SW. In situ hybridization analysis and immunohistochemistry at the light and electron microscopic levels revealed that Slc41a1 is localized to vacuoles in the apical cytoplasm of the proximal tubules. These results suggest that pufferfish Slc41a1 is a Mg2+ transporter involved in renal tubular transepithelial Mg2+ secretion by mediating Mg2+ transport from the cytosol to the vacuolar lumen, and support the hypothesis that Mg2+ secretion is mediated by exocytosis of Mg2+-rich vacuoles to the lumen. [ABSTRACT FROM AUTHOR]

The swimbladder volume is regulated by O2 transfer between the luminal space and the blood In the swimbladder, lactic acid generation by anaerobic glycolysis in the gas gland epithelial cells and its recycling through the rete mirabile bundles of countercurrent capillaries are essential for local blood acidification and oxygen liberation from hemoglobin by the "Root effect." While O2 generation is critical for fish flotation, the molecular mechanism of the secretion and recycling of lactic acid in this critical process is not clear. To clarify molecules that are involved in the blood acidification and visualize the route of lactic acid movement, we analyzed the expression of 17 members of the H+/monocarboxylate transporter (MCT) family in the fugu genome and found that only MCT1b and MCT4b are highly expressed in the fugu swimbladder. Electrophysiological analyses demonstrated that MCT1b is a high-affinity lactate transporter whereas MCT4b is a lowaffinity/ high-conductance lactate transporter. Immunohistochemistry demonstrated that (i) MCT4b expresses in gas gland cells together with the glycolytic enzyme GAPDH at high level and mediate lactic acid secretion by gas gland cells, and (ii) MCT1b expresses in arterial, but not venous, capillary endothelial cells in rete mirabile and mediates recycling of lactic acid in the rete mirabile by solute-specific transcellular transport. These results clarified the mechanism of the blood acidification in the swimbladder by spatially organized two lactic acid transporters MCT4b and MCT1b. [ABSTRACT FROM AUTHOR]

Seawater (SW) contains ~10 mM Ca2+, yet marine fish must drink seawater as their major water source. Thus marine teleosts fish need to excrete Ca2+ to maintain whole body Ca2+ homeostasis. In the intestine, seawater Ca2+ interreacts with epithelial-secreted HCO3- by the intestinal epithelium, and the resulting CaCO3 precipitates, which is rectally excreted. Recently the transporters involved in intestinal HCO3- secretion were identified. Ca2+ is also excreted by the kidney, but the protein(s) involved in renal Ca2+ excretion have not been identified. Here we identified a candidate transporter by using SW pufferfish torafugu (Takifugu rubripes) and its closely related euryhaline species mefugu (Takifugu obscurus), which are becoming useful animal models for studying molecular mechanisms of seawater adaptation. RT-PCR analyses of Na+/Ca2+ exchanger (NCX) family members in various torafugu tissues demonstrated that only NCX2a is highly expressed in the kidney. Renal expression of NCX2a was markedly elevated when mefugu were transferred from freshwater to seawater. In situ hybridization and immunohistochemical analyses indicated that NCX2a is expressed in the proximal tubule at the apical membrane. NCX2a, expressed in Xenopus oocytes, conferred [Ca2+]out- and Na+-dependent currents. These results suggest that NCX2a mediates renal Ca2+ secretion at the apical membrane of renal proximal tubules and has an important role in whole body Ca2+ homeostasis of marine teleosts. [ABSTRACT FROM AUTHOR]

The process of NaCl reabsorption in the distal nephron allows freshwater fishes to excrete hypotonic urine and seawater fishes to excrete urine containing high concentrations of divalent ions; the relevant transporters, however, have not yet been identified. In the mammalian distal nephron, NaCl absorption is mediated by Na+-K+-Cl- cotransporter 2 (NKCC2, Slc12a1) in the thick ascending limb, Na+-Cl- cotransporter (NCC, Slc12a3) in the distal convoluted tubule, and epithelial sodium channel (ENaC) in the collecting duct. In this study, we compared the expression profiles of these proteins in the kidneys of euryhaline and seawater pufferfishes. Mining the fugu genome identified one NKCC2 gene and one NCC gene, but no ENaC gene. RT-PCR and in situ hybridization analyses demonstrated that NKCC2 was highly expressed in the distal tubules and NCC was highly expressed in the collecting ducts of euryhaline pufferfish (mefugu, Takifugu obscurus). On the other hand, the kidney of seawater pufferfish (torafugu, Takifugu rubripes), which lacked distal tubules, expressed very low levels of NCC, and, in the collecting ducts, high levels of NKCC2. Acclimation of mefugu to seawater resulted in a 2.7x decrease in NCC expression, whereas NKCC2 expression was not markedly affected. Additionally, internalization of NCC from the apical surface of the collecting ducts was observed. These results suggest that NaCl reabsorption in the distal nephron of the fish kidney is mediated by NCC and NKCC2 in freshwater and by NKCC2 in seawater. [ABSTRACT FROM AUTHOR]

The kidney of marine teleosts is the major site of Mg(2+) excretion and produces urine with a high Mg(2+) concentration. However, the transporters involved in Mg(2+) excretion are poorly understood. The cyclin M (Cnnm; also known as ancient conserved domain protein) family comprises membrane proteins homologous to the bacterial Mg(2+) and Co(2+) efflux protein, CorC. To understand the molecular mechanism of Mg(2+) homeostasis in marine teleosts, we analyzed the expression of the Cnnm family genes in the seawater (SW) pufferfish, torafugu (Takifugu rubripes), and the closely related euryhaline species, mefugu (Takifugu obscurus). Database mining and phylogenetic analysis indicated that the Takifugu genome contains six members of the Cnnm family: two orthologs of Cnnm1, one of Cnnm2, one of Cnnm3, and two of Cnnm4. RT-PCR analyses indicated that Cnnm2, Cnnm3, and Cnnm4a are expressed in the kidney, whereas other members are mainly expressed in the brain. Renal expression of Cnnm3 was upregulated in SW mefugu, whereas renal expression of Cnnm2 was upregulated in freshwater (FW) mefugu. No significant difference was observed in renal expression of Cnnm4a between SW and FW mefugu. In situ hybridization and immunohistochemical analyses of the SW mefugu kidney revealed that Cnnm3 is expressed in the proximal tubule, and its product localizes to the lateral membrane. When Cnnm3 was expressed in Xenopus laevis oocytes, whole cellular Mg(2+) content and free intracellular Mg(2+) activity significantly decreased. These results suggest that Cnnm3 is involved in body fluid Mg(2+) homeostasis in marine teleosts., (Copyright © 2014 the American Physiological Society.)

The second most abundant cation in seawater (SW), Mg²⁺, is present at concentrations of ~53 mM. Marine teleosts maintain plasma Mg²⁺ concentration at 1-2 mM by excreting Mg²⁺ into the urine. Urine Mg²⁺ concentrations of SW teleosts exceed 70 mM, most of which is secreted by the renal tubular epithelial cells. However, molecular mechanisms of the Mg²⁺ secretion have yet to be clarified. To identify transporters involved in Mg²⁺ secretion, we analyzed the expression of fish homologs of the Slc41 Mg²⁺ transporter family in various tissues of SW pufferfish torafugu (Takifugu rubripes) and its closely related euryhaline species mefugu (Takifugu obscurus). Takifugu genome contained five members of Slc41 genes, and only Slc41a1 was highly expressed in the kidney. Renal expression of Slc41a1 was markedly elevated when mefugu were transferred from fresh water (FW) to SW. In situ hybridization analysis and immunohistochemistry at the light and electron microscopic levels revealed that Slc41a1 is localized to vacuoles in the apical cytoplasm of the proximal tubules. These results suggest that pufferfish Slc41a1 is a Mg²⁺ transporter involved in renal tubular transepithelial Mg²⁺ secretion by mediating Mg²⁺ transport from the cytosol to the vacuolar lumen, and support the hypothesis that Mg²⁺ secretion is mediated by exocytosis of Mg²⁺-rich vacuoles to the lumen.

The process of NaCl reabsorption in the distal nephron allows freshwater fishes to excrete hypotonic urine and seawater fishes to excrete urine containing high concentrations of divalent ions; the relevant transporters, however, have not yet been identified. In the mammalian distal nephron, NaCl absorption is mediated by Na(+)-K(+)-Cl(-) cotransporter 2 (NKCC2, Slc12a1) in the thick ascending limb, Na(+)-Cl(-) cotransporter (NCC, Slc12a3) in the distal convoluted tubule, and epithelial sodium channel (ENaC) in the collecting duct. In this study, we compared the expression profiles of these proteins in the kidneys of euryhaline and seawater pufferfishes. Mining the fugu genome identified one NKCC2 gene and one NCC gene, but no ENaC gene. RT-PCR and in situ hybridization analyses demonstrated that NKCC2 was highly expressed in the distal tubules and NCC was highly expressed in the collecting ducts of euryhaline pufferfish (mefugu, Takifugu obscurus). On the other hand, the kidney of seawater pufferfish (torafugu, Takifugu rubripes), which lacked distal tubules, expressed very low levels of NCC, and, in the collecting ducts, high levels of NKCC2. Acclimation of mefugu to seawater resulted in a 2.7× decrease in NCC expression, whereas NKCC2 expression was not markedly affected. Additionally, internalization of NCC from the apical surface of the collecting ducts was observed. These results suggest that NaCl reabsorption in the distal nephron of the fish kidney is mediated by NCC and NKCC2 in freshwater and by NKCC2 in seawater.