Valuable ingredients and feed toxicity evaluation of Microcystis aeruginosa acidolysis product in mice

This research studied the extraction from Microcystis aeruginosa using hydrochloric acid method as a potentially valuable protein resource from eutrophic lakes. Amino acid composition, residual algal toxins, and heavy metals of the acidolysis product were studied. After 18 h of hydrochloric acid treatment, the product of M. aeruginosa contained 17 amino acids, 51.34% of total amino acid requirements, and 30.25% of the livestock and poultry essential amino acid (Eaa). The residual microcystin-LR (MC-LR) was 0.94 µg kg⁻¹, which was less than WHO drinking water limit of microcystins. The removal ratio of microcystins was higher than 99.99% during the process of hydrolysis. The concentration of heavy metals of the product was in compliance with feed standards. Furthermore, using Horn’s method, Mouse Micronucleus Test and Sperm Shape Abnormality Test were conducted to study the forage safety of the product. Half lethal dose (LD₅₀) of acidolysis product in mice was >9.09 g kg⁻¹ body weight, actually belonging to non-toxic grade. Every dose treatment did not significantly increase activities of alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and γ-glutamyltransferase (γ-GT). The results of both micronucleus test and sperm shape abnormality test were negative, which suggested the product with no mutagenicity and sperm malformation effects. This study indicated that the acidolysis product of M. aeruginosa was safe to be used as a feed ingredient.     

Toxicity of non-steroidal anti-inflammatory drugs to Gyps vultures: a new threat from ketoprofen

Three Gyps vulture species are on the brink of extinction in South Asia owing to the veterinary non-steroidal anti-inflammatory drug (NSAID) diclofenac. Carcasses of domesticated ungulates are the main food source for Asia''s vultures and birds die from kidney failure after consuming diclofenac-contaminated tissues. Here, we report on the safety testing of the NSAID ketoprofen, which was not reported to cause mortality in clinical treatment of scavenging birds and is rapidly eliminated from livestock tissues. Safety testing was undertaken using captive non-releasable Cape griffon vultures (Gyps coprotheres) and wild-caught African white-backed vultures (G. africanus), both previously identified as susceptible to diclofenac and suitable surrogates. Ketoprofen doses ranged from 0.5 to 5 mg kg⁻¹ vulture body weight, based upon recommended veterinary guidelines and maximum levels of exposure for wild vultures (estimated as 1.54 mg kg⁻¹). Doses were administered by oral gavage or through feeding tissues from cattle dosed with ketoprofen at 6 mg kg⁻¹ cattle body weight, before slaughter. Mortalities occurred at dose levels of 1.5 and 5 mg kg⁻¹ vulture body weight (within the range recommended for clinical treatment) with the same clinical signs as observed for diclofenac. Surveys of livestock carcasses in India indicate that toxic levels of residual ketoprofen are already present in vulture food supplies. Consequently, we strongly recommend that ketoprofen is not used for veterinary treatment of livestock in Asia and in other regions of the world where vultures access livestock carcasses. The only alternative to diclofenac that should be promoted as safe for vultures is the NSAID meloxicam.     

Potential for aflatoxin B1 and B2 production by Aspergillus flavus strains isolated from rice samples

In this study, we investigated the potential for aflatoxin B₁ (AFB₁) and B₂ (AFB₂) production in rice grain by 127 strains of Aspergillus flavus isolated from rice grains collected from China. These strains were inoculated onto rice grains and incubated at 28 °C for 21 days. AFB₁ and AFB₂ were extracted and quantified by high-performance liquid chromatography coupled with fluorescence detection. Among the tested strains, 37% produced AFB₁ and AFB₂ with levels ranging from 175 to 124 101 μg kg⁻¹ for AFB₁ and from not detected to 10 329 μg kg⁻¹ for AFB₂. The mean yields of these isolates were 5884 μg kg⁻¹ for AFB₁ and 1968 μg kg⁻¹ for AFB₂. Overall, most of the aflatoxigenic strains produced higher levels of AFB₁ than AFB₂ in rice. The obtained information is useful for assessing the risk of aflatoxin contamination in rice samples.     

Improving key enzyme activities and quality of rice under various methods of zinc application

Zinc (Zn) is an important micronutrient for the physiology of plants. It is poorly available to the plants in soil solution. A pot experiment was conducted to evaluate effectiveness of various Zn application methods on key enzyme activities and protein content of two contrasting rice genotypes viz., PD16 (Zn efficient) and NDR359 (Zn inefficient). The treatments were, control (0 mg Zn kg⁻¹ soil), soil application (5 mg Zn kg⁻¹ soil), foliar application (0.5 % ZnSO₄ + 0.25 % lime at 30, 60 and 90 days after transplanting), soil (5 mg Zn kg⁻¹ soil) + foliar application of 0.5 % ZnSO₄ + 0.25 % lime at 30, 60 and 90 days after transplanting. Among all the methods tested soil+foliar application of Zn fertilizers was found most effective in increasing superoxide dismutase (SOD) and carbonic anhydrase (CA) activities as well as chlorophyll and protein content in both the rice varieties. NDR359, showed higher enzyme activities and more chlorophyll content in leaves than PD16, when Zn was applied either through foliar spray alone or in soil along with foliar application. Regarding the protein content in grains, PD16 showed higher protein content than NDR359, thus showed better translocation of Zn from leaves to grains.     

Repellent,larvicidal and adulticidal activities of essential oil from Dai medicinal plant Zingiber cassumunar against Aedes albopictus

Zingiber cassumunar is an important plant used in traditional medicine and as a natural mosquito repellent. However, the compounds responsible for the repellent activity of the plant are still unknown. The aim of the study is to identify the components of Z. cassumunar essential oil that show repellent activity against Aedes albopictus. We also evaluated the larvicidal and adulticidal activities of Z. cassumunar essential oil against Ae. albopictus. In-cage mosquito repellent experiments showed that Z. cassumunar essential oil possessed moderate repellent activity with a minimum effective dose (MED) of 0.16 ± 0.01 mg/cm², compared to reference standard N,N-diethyl-3-methylbenzamide (DEET, 0.03 ± 0.01 mg/cm²). Bioassay-guided fractionation identified the major active compound of Z. cassumunar essential oil as (−)-terpinen-4-ol (1) (MED: 0.19 ± 0 mg/cm²). We also found that Z. cassumunar essential oil showed moderate larvicidal activity against first instar larvae of Ae. albopictus with a LC₅₀ (50% lethal concentration) of 44.9 μg/L after 24 h. Fumigation bioassays showed that Z. cassumunar essential oil exhibits moderate adulticidal activity against Ae. albopictus with a LC₅₀ of 5.44%, while (−)-terpinen-4-ol showed significant adulticidal activity with a LC₅₀ of 2.10% after 24 h. This study verifies that the Z. cassumunar essential oil has mosquito repellent activity, and that (−)-terpinen-4-ol is mainly responsible for this activity. Furthermore, this study provides scientific support for the folk usage of Z. cassumunar essential oil as mosquito repellent and indicates that Z. cassumunar essential oil and (−)-terpinen-4-ol can be used as plant-derived repellents and insecticides for mosquito control.     

Soil TPH Concentration Estimation Using Vegetation Indices in an Oil Polluted Area of Eastern China

Assessing oil pollution using traditional field-based methods over large areas is difficult and expensive. Remote sensing technologies with good spatial and temporal coverage might provide an alternative for monitoring oil pollution by recording the spectral signals of plants growing in polluted soils. Total petroleum hydrocarbon concentrations of soils and the hyperspectral canopy reflectance were measured in wetlands dominated by reeds (Phragmites australis) around oil wells that have been producing oil for approximately 10 years in the Yellow River Delta, eastern China to evaluate the potential of vegetation indices and red edge parameters to estimate soil oil pollution. The detrimental effect of oil pollution on reed communities was confirmed by the evidence that the aboveground biomass decreased from 1076.5 g m⁻² to 5.3 g m⁻² with increasing total petroleum hydrocarbon concentrations ranging from 9.45 mg kg⁻¹ to 652 mg kg⁻¹. The modified chlorophyll absorption ratio index (MCARI) best estimated soil TPH concentration among 20 vegetation indices. The linear model involving MCARI had the highest coefficient of determination (R ² = 0.73) and accuracy of prediction (RMSE = 104.2 mg kg⁻¹). For other vegetation indices and red edge parameters, the R² and RMSE values ranged from 0.64 to 0.71 and from 120.2 mg kg⁻¹ to 106.8 mg kg⁻¹ respectively. The traditional broadband normalized difference vegetation index (NDVI), one of the broadband multispectral vegetation indices (BMVIs), produced a prediction (R ² = 0.70 and RMSE = 110.1 mg kg⁻¹) similar to that of MCARI. These results corroborated the potential of remote sensing for assessing soil oil pollution in large areas. Traditional BMVIs are still of great value in monitoring soil oil pollution when hyperspectral data are unavailable.     

Culturable Heavy Metal-Resistant and Plant Growth Promoting Bacteria in V-Ti Magnetite Mine Tailing Soil from Panzhihua,China

To provide a basis for using indigenous bacteria for bioremediation of heavy metal contaminated soil, the heavy metal resistance and plant growth-promoting activity of 136 isolates from V-Ti magnetite mine tailing soil were systematically analyzed. Among the 13 identified bacterial genera, the most abundant genus was Bacillus (79 isolates) out of which 32 represented B. subtilis and 14 B. pumilus, followed by Rhizobium sp. (29 isolates) and Ochrobactrum intermedium (13 isolates). Altogether 93 isolates tolerated the highest concentration (1000 mg kg⁻¹) of at least one of the six tested heavy metals. Five strains were tolerant against all the tested heavy metals, 71 strains tolerated 1,000 mg kg⁻¹ cadmium whereas only one strain tolerated 1,000 mg kg⁻¹ cobalt. Altogether 67% of the bacteria produced indoleacetic acid (IAA), a plant growth-promoting phytohormone. The concentration of IAA produced by 53 isolates was higher than 20 µg ml⁻¹. In total 21% of the bacteria produced siderophore (5.50–167.67 µg ml⁻¹) with two Bacillus sp. producing more than 100 µg ml⁻¹. Eighteen isolates produced both IAA and siderophore. The results suggested that the indigenous bacteria in the soil have beneficial characteristics for remediating the contaminated mine tailing soil.     

Novel biopesticide based on a spider venom peptide shows no adverse effects on honeybees

Evidence is accumulating that commonly used pesticides are linked to decline of pollinator populations; adverse effects of three neonicotinoids on bees have led to bans on their use across the European Union. Developing insecticides that pose negligible risks to beneficial organisms such as honeybees is desirable and timely. One strategy is to use recombinant fusion proteins containing neuroactive peptides/proteins linked to a ‘carrier’ protein that confers oral toxicity. Hv1a/GNA (Galanthus nivalis agglutinin), containing an insect-specific spider venom calcium channel blocker (ω-hexatoxin-Hv1a) linked to snowdrop lectin (GNA) as a ‘carrier’, is an effective oral biopesticide towards various insect pests. Effects of Hv1a/GNA towards a non-target species, Apis mellifera, were assessed through a thorough early-tier risk assessment. Following feeding, honeybees internalized Hv1a/GNA, which reached the brain within 1 h after exposure. However, survival was only slightly affected by ingestion (LD₅₀ > 100 µg bee⁻¹) or injection of fusion protein. Bees fed acute (100 µg bee⁻¹) or chronic (0.35 mg ml⁻¹) doses of Hv1a/GNA and trained in an olfactory learning task had similar rates of learning and memory to no-pesticide controls. Larvae were unaffected, being able to degrade Hv1a/GNA. These tests suggest that Hv1a/GNA is unlikely to cause detrimental effects on honeybees, indicating that atracotoxins targeting calcium channels are potential alternatives to conventional pesticides.     

TAp73 is required for macrophage-mediated innate immunity and the resolution of inflammatory responses

The multiple isoforms of p73, a member of the p53 family, share the ability to modulate p53 activities but also have unique properties, leading to a complex and poorly understood functional network. In vivo, p73 isoforms have been implicated in tumor suppression (TAp73^−/− mice), DNA damage (ΔNp73^−/− mice) and development (p73^−/− mice). In this study, we investigated whether TAp73 contributes to innate immunity and septic shock. In response to a lethal lipopolysaccharide (LPS) challenge, TAp73^−/− mice showed higher blood levels of proinflammatory cytokines and greater mortality than their wild-type littermates. In vitro, TAp73^−/− macrophages exhibited elevated production of tumor necrosis factor alpha , interleukin-6 and macrophage inflammatory protein-2 as well as prolonged survival, decreased phagocytosis and increased major histocompatibility complex class II expression. Mice depleted of endogenous macrophages and reconstituted with TAp73^−/− macrophages showed increased sensitivity to LPS challenge. These results suggest that macrophage polarization is altered in the absence of TAp73 such that maintenance of the M1 effector phenotype is prolonged at the expense of the M2 phenotype, thus impairing resolution of the inflammatory response. Our data indicate that TAp73 has a role in macrophage polarization and innate immunity, enhancing the action field of this important regulatory molecule.     

Mild ammonium stress increases chlorophyll content in Arabidopsis thaliana

Nitrate (NO₃⁻) and ammonium (NH₄⁺) are the main forms of nitrogen available in the soil for plants. Excessive NH₄⁺ accumulation in tissues is toxic for plants and exclusive NH₄⁺-based nutrition enhances this effect. Ammonium toxicity syndrome commonly includes growth impairment, ion imbalance and chlorosis among others. In this work, we observed high intraspecific variability in chlorophyll content in 47 Arabidopsis thaliana natural accessions grown under 1 mM NH₄⁺ or 1 mM NO₃⁻ as N-source. Interestingly, chlorophyll content increased in every accession upon ammonium nutrition. Moreover, this increase was independent of ammonium tolerance capacity. Thus, chlorosis seems to be an exclusive effect of severe ammonium toxicity while mild ammonium stress induces chlorophyll accumulation.     

Evolutionary rescue and adaptation to abrupt environmental change depends upon the history of stress

Whether evolution will be rapid enough to rescue declining populations will depend upon population size, the supply of genetic variation, the degree of maladaptation and the historical direction of selection. We examined whether the level of environmental stress experienced by a population prior to abrupt environmental change affects the probability of evolutionary rescue (ER). Hundreds of populations of two species of yeast, Saccharomyces cerevisiae and Saccharomyces paradoxus were exposed to a range of sublethal concentrations of salt for approximately a hundred generations before transfer to a concentration of salt lethal to the ancestor (150 g l^–1 NaCl). The fitness of surviving populations of both species was a quadratic function of yield: fitness was greatest for large populations that had been selected on low salt concentrations (less than 20 g l⁻¹ NaCl) and small populations that had adapted to high salt (more than 80 g l⁻¹ NaCl). However, differences occurred between species in the probability of ER. The frequency of ER was positively correlated with salt concentration for S. cerevisiae, but negatively correlated with salt concentration in S. paradoxus. These results not only demonstrate that past environmental conditions can determine the probability of ER after abrupt environmental change, but also suggest that there may even be differences between closely related species that are worth further exploration.     

Nitrite oxidation in the upper water column and oxygen minimum zone of the eastern tropical North Pacific Ocean

Nitrogen (N) is an essential nutrient in the sea and its distribution is controlled by microorganisms. Within the N cycle, nitrite (NO₂⁻) has a central role because its intermediate redox state allows both oxidation and reduction, and so it may be used by several coupled and/or competing microbial processes. In the upper water column and oxygen minimum zone (OMZ) of the eastern tropical North Pacific Ocean (ETNP), we investigated aerobic NO₂⁻ oxidation, and its relationship to ammonia (NH₃) oxidation, using rate measurements, quantification of NO₂⁻-oxidizing bacteria via quantitative PCR (QPCR), and pyrosequencing. ¹⁵NO₂⁻ oxidation rates typically exhibited two subsurface maxima at six stations sampled: one located below the euphotic zone and beneath NH₃ oxidation rate maxima, and another within the OMZ. ¹⁵NO₂⁻ oxidation rates were highest where dissolved oxygen concentrations were <5 μM, where NO₂⁻ accumulated, and when nitrate (NO₃⁻) reductase genes were expressed; they are likely sustained by NO₃⁻ reduction at these depths. QPCR and pyrosequencing data were strongly correlated (r²=0.79), and indicated that Nitrospina bacteria numbered up to 9.25% of bacterial communities. Different Nitrospina groups were distributed across different depth ranges, suggesting significant ecological diversity within Nitrospina as a whole. Across the data set, ¹⁵NO₂⁻ oxidation rates were decoupled from ¹⁵NH₄⁺ oxidation rates, but correlated with Nitrospina (r²=0.246, P<0.05) and NO₂⁻ concentrations (r²=0.276, P<0.05). Our findings suggest that Nitrospina have a quantitatively important role in NO₂⁻ oxidation and N cycling in the ETNP, and provide new insight into their ecology and interactions with other N-cycling processes in this biogeochemically important region of the ocean.     

The phenotypes of ATG9, ATG16 and ATG9/16 knock-out mutants imply autophagy-dependent and -independent functions

Macroautophagy is a highly conserved intracellular bulk degradation system of all eukaryotic cells. It is governed by a large number of autophagy proteins (ATGs) and is crucial for many cellular processes. Here, we describe the phenotypes of Dictyostelium discoideum ATG16⁻ and ATG9⁻/16⁻ cells and compare them to the previously reported ATG9⁻ mutant. ATG16 deficiency caused an increase in the expression of several core autophagy genes, among them atg9 and the two atg8 paralogues. The single and double ATG9 and ATG16 knock-out mutants had complex phenotypes and displayed severe and comparable defects in pinocytosis and phagocytosis. Uptake of Legionella pneumophila was reduced. In addition, ATG9⁻ and ATG16⁻ cells had dramatic defects in autophagy, development and proteasomal activity which were much more severe in the ATG9⁻/16⁻ double mutant. Mutant cells showed an increase in poly-ubiquitinated proteins and contained large ubiquitin-positive protein aggregates which partially co-localized with ATG16-GFP in ATG9⁻/16⁻ cells. The more severe autophagic, developmental and proteasomal phenotypes of ATG9⁻/16⁻ cells imply that ATG9 and ATG16 probably function in parallel in autophagy and have in addition autophagy-independent functions in further cellular processes.     

Expression of Ca2+-permeable two-pore channels rescues NAADP signalling in TPC-deficient cells

The second messenger NAADP triggers Ca²⁺ release from endo-lysosomes. Although two-pore channels (TPCs) have been proposed to be regulated by NAADP, recent studies have challenged this. By generating the first mouse line with demonstrable absence of both Tpcn1 and Tpcn2 expression (Tpcn1/2^−/−), we show that the loss of endogenous TPCs abolished NAADP-dependent Ca²⁺ responses as assessed by single-cell Ca²⁺ imaging or patch-clamp of single endo-lysosomes. In contrast, currents stimulated by PI(3,5)P₂ were only partially dependent on TPCs. In Tpcn1/2^−/− cells, NAADP sensitivity was restored by re-expressing wild-type TPCs, but not by mutant versions with impaired Ca²⁺-permeability, nor by TRPML1. Another mouse line formerly reported as TPC-null likely expresses truncated TPCs, but we now show that these truncated proteins still support NAADP-induced Ca²⁺ release. High-affinity [³²P]NAADP binding still occurs in Tpcn1/2^−/− tissue, suggesting that NAADP regulation is conferred by an accessory protein. Altogether, our data establish TPCs as Ca²⁺-permeable channels indispensable for NAADP signalling.     

Intra- specific variation in response of Jatropha (Jatropha curcas L.) to elevated CO2 conditions

Twenty genotypes of Jatropha collected from diverse eco-geographic regions from the states of Chhattisgarh (3), Andhra Pradesh (12), Rajasthan (4) and Uttarakhand (1) of India were subjected to elevated CO₂ conditions. All the genotypes showed significant difference (p < 0.05 and 0.01) in the phenotypic traits in both the environments (elevated and ambient) and genotype x environment interaction. Among the physiological traits recorded, maximum photosynthetic rate was observed in IC565048 (48.8 μmol m⁻² s⁻¹) under ambient controlled conditions while under elevated conditions maximum photosynthetic rate was observed in IC544678 (41.3 μmol m⁻² s⁻¹), and there was no significant difference in the genotype x environment interaction. Stomatal conductance (Gs) emerged as the key factor as it recorded significant difference among the genotypes, between the environments and also genotype x environment interaction. The Gs and transpiration (E) recorded a significant decline in the genotypes under the elevated CO₂ condition over the ambient control. Under elevated CO₂ conditions, the minimum values recorded for Gs and E were 0.03 mmol m⁻² s⁻¹ and 0.59 mmol m⁻² s⁻¹ respectively in accession IC565039, while the maximum values for Gs and E were 1.8 mmol m⁻² s⁻¹ and 11.5 mmol m⁻² s⁻¹ as recorded in accession IC544678. The study resulted in the identification of potential climate ready genotypes viz. IC471314, IC544654, IC541634, IC544313, and IC471333 for future use.     

Lanthanum from a Modified Clay Used in Eutrophication Control Is Bioavailable to the Marbled Crayfish (Procambarus fallax f. virginalis)

To mitigate eutrophication in fresh standing waters the focus is on phosphorus (P) control, i.e. on P inflows to a lake as well as a lake''s sediment as internal P source. The in-lake application of the lanthanum (La) modified clays – i.e. La modified bentonite (Phoslock) or La modified kaolinite, aim at dephosphatising the water column and at reducing the release of P from a lake''s sediment. Application of these clays raises the question whether La from these clays can become bioavailable to biota. We investigated the bioavailability of La from Phoslock in a controlled parallel groups experiment in which we measured the La in carapace, gills, ovaries, hepatopancreas and abdominal muscle after 0, 14 and 28 days of exposure to Phoslock. Expressing the treatment effect as the difference of the median concentration between the two treatment groups (Phoslock minus control group) yield the following effects, the plus sign (+) indicating an increase, concentrations in µg g⁻¹ dry weight: Day 14: carapace +10.5 µg g⁻¹, gills +112 µg g⁻¹, ovaries +2.6 µg g⁻¹, hepatopancreas +32.9 µg g⁻¹ and abodminal muscle +3.2 µg g⁻¹. Day 28: carapace +17.9 µg g⁻¹; gills +182 µg g⁻¹; ovaries +2.2 µg g⁻¹; hepatopancreas +41.9 µg g⁻¹ and abodminal muscle +7.6 µg g⁻¹, all effects were statistically significant. As La from Phoslock is bio-available to and taken up by the marbled crayfishes (Procambarus fallax f. virginalis), we advocate that the application of in-lake chemical water treatments to mitigate eutrophication should be accompanied by a thorough study on potential side effects.     

Phosphorus Accumulation and Sorption in Calcareous Soil under Long-Term Fertilization

Application of phosphorus (P) fertilizers to P-deficient soils can also result in P accumulation. In this study, soil P status and P uptake by apple trees were investigated in 5-, 10-, and 15-year-old orchards in the semi-arid Loess Plateau, China, and subset soils with different soil P statuses (14–90 Olsen-P mg kg⁻¹) were selected to evaluate the characteristic P adsorption. Due to the low P-use efficiency (4–6%), total soil P increased from 540 mg kg⁻¹ to 904 mg kg⁻¹, Olsen-P ranged from 3.4 mg kg⁻¹ to 30.7 mg kg⁻¹, and CaCl₂-P increased from less than 0.1 mg kg⁻¹ to 0.66 mg kg⁻¹ under continuous P fertilization. The P sorption isotherms for each apple orchard were found to fit the Langmuir isotherm model (R ² = 0.91–0.98). K (binding energy) and Q _m (P sorption maximum) decreased, whereas DPS (degree of phosphorus sorption) increased with increasing P concentration. CaCl₂-P increased significantly with the increase of Olsen-P, especially above the change point of 46.1 mg kg⁻¹. Application of surplus P could result in P enrichment in P-deficient soil which has high P fixation capacity, thus posing a significant environmental risk.     

Tip30 controls differentiation of murine mammary luminal progenitor to estrogen receptor-positive luminal cell through regulating FoxA1 expression

Estrogen receptor-alpha positive (ER⁺) breast cancers comprise the majority of human breast cancers, but molecular mechanisms underlying this subtype of breast cancers remain poorly understood. Here, we show that ER⁺ mammary luminal tumors arising in Tip30^−/−MMTV-Neu mice exhibited increased enrichment of luminal progenitor gene signature. Deletion of the Tip30 gene increased proportion of mammary stem and progenitor cell populations, and raised susceptibility to ER⁺ mammary luminal tumors in female Balb/c mice. Moreover, Tip30^−/− luminal progenitors displayed increases in propensity to differentiate to mature ER⁺ luminal cells and FoxA1 expression. Knockdown of FoxA1 expression in Tip30^−/− progenitors by shRNA specific for FoxA1 reduced their differentiation toward ER⁺ mature luminal cells. Taken together, our results suggest that TIP30 is a key regulator for maintaining ER⁺ and ER⁻luminal pools in the mammary luminal lineage, and loss of it promotes expansion of ER⁺ luminal progenitors and mature cells and ER⁺ mammary tumorigenesis.