Due to the tonic and nutritive virtues of sea cucumbers, increased commercial aquaculture has resulted in the expansion of breeding ponds, a primary form of sea cucumber production. Expansion of such ...production methods has led to increased settling of organic wastes onto the seabed, resulting in enriched sediments. Nitzschia sp. serves as an edible sea cucumber feed. Release characteristics of nitrogen (N) and phosphorus (P) from sediments in the presence of different biomass densities of Nitzschia sp. were studied via laboratory static cultures. pH and dissolved oxygen (DO) in the overlying water and biochemical components (i.e., protein, chlorophyll a) of Nitzschia sp. were assessed. When the biomass of Nitzschia sp. was more than (2–5) × 104 ind/cm2, the release of N and P nutrients was significantly promoted; additionally, the DO content of the overlying water was relatively high and the pH was relatively stable, which favoured the accumulation of proteins and chlorophyll a in Nitzschia sp. The results indicated that Nitzschia sp. promotes the release of N and P in sediments while absorbing them to maintain their own growth and promote the accumulation of nutrients, such as proteins, for the sea cucumbers. At the same time, the algae release oxygen, increasing the DO of the overlying water, providing a healthy breeding environment for the sea cucumbers. Application of Nitzschia sp. has the potential to reduce environmental harm caused by sea cucumber cultivation and thus achieve sustainable aquaculture.
•A recombinant IHNV virus expressing VP2 gene of IPNV was successfully constructed.•The recombinant virus showed significant protection efficacy against IHNV and IPNV.•The recombinant virus induced ...upregulation of innate and adaptive immune responses.•The recombinant virus could be a vaccine candidate protecting rainbow trout against two or more diseases.
Infectious pancreatic necrosis virus (IPNV) and infectious hematopoietic necrosis virus (IHNV) are two common viral pathogens that cause severe economic losses in all salmonid species in culture, but especially in rainbow trout. Although vaccines against both diseases have been commercialized in some countries, no such vaccines are available for them in China. In this study, a recombinant virus was constructed using the IHNV U genogroup Blk94 virus as a backbone vector to express the antigenic gene, VP2, from IPNV via the reverse genetics system. The resulting recombinant virus (rBlk94-VP2) showed stable biological characteristics as confirmed by virus growth kinetic analyses, pathogenicity analyses, indirect immunofluorescence assays and western blotting. Rainbow trout were immunized with rBlk94-VP2 and then challenged with the IPNV ChRtm213 strain and the IHNV Sn1203 strain on day 45 post-vaccination. A significantly higher survival rate against IHNV was obtained in the rBlk94-VP2 group on day 45 post-vaccination (86%) compared with the PBS mock immunized group (2%). Additionally, IPNV loads decreased significantly in the rBlk94-VP2 immunized group in the liver (28.6-fold to 36.5-fold), anterior kidney (21.7-fold to 44.2-fold), and spleen (14.9-fold to 22.7-fold), as compared with the PBS mock control group. The mRNA transcripts for several innate and adaptive immune-related proteins (IFN-γ, IFN-1, Mx-1, CD4, CD8, IgM, and IgT) were also significantly upregulated after rBlk94-VP2 vaccination, and neutralizing antibodies against both IHNV and IPNV were induced on day 45 post-vaccination. Collectively, our results suggest that this recombinant virus could be developed as a vaccine vector to protect rainbow trout against two or more diseases, and our approach lays the foundations for developing live vaccines for rainbow trout.
•Two different starch graft copolymers were synthesized.•Starch graft copolymers act as both dispersants and flocculants for lizardite in the flotation separation.•Starch graft copolymers disperse ...lizardite from pentlandite surface by reversing the zeta potential of lizardite.•Starch graft copolymers flocculate lizardite particles and hence decrease the turbidity value of lizardite.
This paper investigates the detrimental effect of lizardite surface characteristics on pentlandite flotation. To reduce the effect, two different starch graft copolymers, starch–graft–polyacrylamide (S–g–PAM) and starch–graft–polyacrylic acid (S–g–PAA) were synthesized as depressants for lizardite. The flotation results show that at pH value of 8, where the flotation of lizardite and pentlandite are routinely performed, S–g–PAM and S–g–PAA improve pentlandite recovery efficiently, compared with the traditional depressant carboxymethyl cellulose (CMC). Experimental results demonstrate that S–g–PAM and S–g–PAA disperse the hydrophilic lizardite particles from the pentlandite surface and also flocculate lizardite particles.
The testing association of environmental variables with genetic and epigenetic variation could be crucial to deciphering the effects of environmental factors playing roles as selective drivers in ...ecological speciation. Although ecological speciation may occur in closely related species, species boundaries may not be established over a short evolutionary timescale. Here, we investigated the genetic and epigenetic variations using amplified fragment length polymorphism (AFLP) and methylation-sensitive amplification polymorphism (MSAP), respectively, and tested their associations with environmental variables in populations of four closely related species in the
complex. No distinctive species relationships were found using genetic clustering analyses, neighbor-joining tree, and neighbor-net tree based on the total AFLP variation, which is suggestive of the incomplete lineage sorting of ancestral variation. Nonetheless, strong isolation-by-environment and adaptive divergence were revealed, despite the significant isolation-by-distance. Annual mean temperature, elevation, normalized difference vegetation index, and annual total potential evapotranspiration were found to be the most important environmental variables explaining outlier genetic and epigenetic variations. Our results suggest that the four closely related species of the
complex share the polymorphism of their ancestor, but reproductive isolation due to ecological speciation can occur if local environmental divergence persists over time.
The testing association of environmental variables with genetic and epigenetic variation could be crucial to deciphering the effects of environmental factors playing roles as selective drivers in ...ecological speciation. Although ecological speciation may occur in closely related species, species boundaries may not be established over a short evolutionary timescale. Here, we investigated the genetic and epigenetic variations using amplified fragment length polymorphism (AFLP) and methylation-sensitive amplification polymorphism (MSAP), respectively, and tested their associations with environmental variables in populations of four closely related species in the R. pseudochrysanthum complex. No distinctive species relationships were found using genetic clustering analyses, neighbor-joining tree, and neighbor-net tree based on the total AFLP variation, which is suggestive of the incomplete lineage sorting of ancestral variation. Nonetheless, strong isolation-by-environment and adaptive divergence were revealed, despite the significant isolation-by-distance. Annual mean temperature, elevation, normalized difference vegetation index, and annual total potential evapotranspiration were found to be the most important environmental variables explaining outlier genetic and epigenetic variations. Our results suggest that the four closely related species of the R. pseudochrysanthum complex share the polymorphism of their ancestor, but reproductive isolation due to ecological speciation can occur if local environmental divergence persists over time.
The PML/RARα fusion protein is the oncogenic driver in acute promyelocytic leukemia (APL). Although most APL cases are cured by PML/RARα-targeting therapy, relapse and resistance can occur due to ...drug-resistant mutations. Here we report that thermal stress destabilizes the PML/RARα protein, including clinically identified drug-resistant mutants. AML1/ETO and TEL/AML1 oncofusions show similar heat shock susceptibility. Mechanistically, mild hyperthermia stimulates aggregation of PML/RARα in complex with nuclear receptor corepressors leading to ubiquitin-mediated degradation via the SIAH2 E3 ligase. Hyperthermia and arsenic therapy destabilize PML/RARα via distinct mechanisms and are synergistic in primary patient samples and
, including three refractory APL cases. Collectively, our results suggest that by taking advantage of a biophysical vulnerability of PML/RARα, thermal therapy may improve prognosis in drug-resistant or otherwise refractory APL. These findings serve as a paradigm for therapeutic targeting of fusion oncoprotein-associated cancers by hyperthermia.
Hyperthermia destabilizes oncofusion proteins including PML/RARα and acts synergistically with standard arsenic therapy in relapsed and refractory APL. The results open up the possibility that heat shock sensitivity may be an easily targetable vulnerability of oncofusion-driven cancers.
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In familial pulmonary arterial hypertension (FPAH), the autosomal dominant disease-causing BMPR2 mutation is only 20% penetrant, suggesting that genetic variation provides modifiers that alleviate ...the disease. Here, we used comparison of induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) from three families with unaffected mutation carriers (UMCs), FPAH patients, and gender-matched controls to investigate this variation. Our analysis identified features of UMC iPSC-ECs related to modifiers of BMPR2 signaling or to differentially expressed genes. FPAH-iPSC-ECs showed reduced adhesion, survival, migration, and angiogenesis compared to UMC-iPSC-ECs and control cells. The “rescued” phenotype of UMC cells was related to an increase in specific BMPR2 activators and/or a reduction in inhibitors, and the improved cell adhesion could be attributed to preservation of related signaling. The improved survival was related to increased BIRC3 and was independent of BMPR2. Our findings therefore highlight protective modifiers for FPAH that could help inform development of future treatment strategies.
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•Normal function distinguishes iPSC-ECs from unaffected BMPR2 mutation carrier (UMC)•Protective BMPR2 modifiers preserve pP38 signaling and adhesion in UMC iPSC-ECs•Increased BIRC3 in UMC iPSC-ECs is related to normalization of EC survival•Correction of the BMPR2 mutation in PAH iPSC-ECs restores signaling and EC function
As part of the NHLBI NextGen consortium, Gu et al. report protective mechanisms of potential therapeutic significance in unaffected BMPR2 mutation carrier (UMC) iPSC-derived endothelial cells (iPSC-ECs) versus iPSC-ECs from family members with pulmonary arterial hypertension (FPAH). Their findings about changes in specific regulators could inform future therapy development.
► We compared immune responses elicited by a vaccine EIAV
DLV121 or virulent EIAV
LN40 strain. ► Infection of EIAV
DLV121 and sublethal dose of EIAV
LN40 resulted in similar plasma viral loads. ► ...EIAV
DLV121 stimulated significantly higher level of conformational dependent env and neutralizing antibodies. ► EIAV
DLV121 significantly enhanced CD4
+ T cell responses especially in the early stage. ► p26 Capsid-specific antibody appeared to be a marker of protective immunity to EIAV.
The EIAV (equine infectious anemia virus) multi-species attenuated vaccine EIAV
DLV121 successfully prevented the spread of equine infectious anemia (EIA) in China in the 1970s and provided an excellent model for the study of protective immunity to lentiviruses. In this study, we compared immune responses induced by EIAV
DLV121 to immunity elicited by the virulent EIAV
LN40 strain and correlated immune responses to protection from infection. Horses were randomly grouped and inoculated with either EIAV
DLV121 (Vaccinees, Vac) or a sublethal dose of EIAV
LN40 (asymptomatic carriers, Car). Car horses became EIAV
LN40 carriers without disease symptoms. Two of the four Vac horses were protected against infection and the other two had delayed onset or reduced severity of EIA with a lethal EIAV
LN40 challenge 5.5
months post initial inoculation. In contrast, all three Car animals developed acute EIA and two succumbed to death. Specific humoral and cellular immune responses in both Vac and Car groups were evaluated for potential correlations with protection. These analyses revealed that although plasma viral loads remained between 10
3 and 10
5
copies/ml for both groups before EIAV
LN40 challenge, Vac-treated animals developed significantly higher levels of conformational dependent, Env-specific antibody, neutralizing antibody as well as significantly elevated CD4
+ T cell proliferation and IFN-γ-secreting CD8
+ T cells than those observed in EIAV
LN40 asymptomatic carriers. Further analysis of protected and unprotected cases in vaccinated horses identified that cellular response parameters and the reciprocal anti-p26-specific antibody titers closely correlated with protection against infection with the pathogenic EIAV
LN40. These data provide a better understanding of protective immunity to lentiviruses.
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