Transgenic studies reveal the positive role of LeEIL-1 in regulating shikonin biosynthesis in Lithospermum erythrorhizon hairy roots

Time-course accumulation of shikonin in four typical hairy root lines. Value of Ei-19 or EO-13 is significantly different from that of the control line WT-1 or EV-9 at each time point from 3 to 12 days, respectively (Student’s t-test, P < 0.05). (TIF 125 kb

CARM1 Methylates Chromatin Remodeling Factor BAF155 to Enhance Tumor Progression and Metastasis

SummaryCoactivator-associated arginine methyltransferase 1 (CARM1), a coactivator for various cancer-relevant transcription factors, is overexpressed in breast cancer. To elucidate the functions of CARM1 in tumorigenesis, we knocked out CARM1 from several breast cancer cell lines using Zinc-Finger Nuclease technology, which resulted in drastic phenotypic and biochemical changes. The CARM1 KO cell lines enabled identification of CARM1 substrates, notably the SWI/SNF core subunit BAF155. Methylation of BAF155 at R1064 was found to be an independent prognostic biomarker for cancer recurrence and to regulate breast cancer cell migration and metastasis. Furthermore, CARM1-mediated BAF155 methylation affects gene expression by directing methylated BAF155 to unique chromatin regions (e.g., c-Myc pathway genes). Collectively, our studies uncover a mechanism by which BAF155 acquires tumorigenic functions via arginine methylation

Rapid discrimination of Bifidobacterium longum subspecies based on MALDI-TOF MS and machine learning

Although MALDI-TOF mass spectrometry (MS) is widely known as a rapid and cost-effective reference method for identifying microorganisms, its commercial databases face limitations in accurately distinguishing specific subspecies of Bifidobacterium. This study aimed to explore the potential of MALDI-TOF MS protein profiles, coupled with prediction methods, to differentiate between Bifidobacterium longum subsp. infantis (B. infantis) and Bifidobacterium longum subsp. longum (B. longum). The investigation involved the analysis of mass spectra of 59 B. longum strains and 41 B. infantis strains, leading to the identification of five distinct biomarker peaks, specifically at m/z 2,929, 4,408, 5,381, 5,394, and 8,817, using Recurrent Feature Elimination (RFE). To facilate classification between B. longum and B. infantis based on the mass spectra, machine learning models were developed, employing algorithms such as logistic regression (LR), random forest (RF), and support vector machine (SVM). The evaluation of the mass spectrometry data showed that the RF model exhibited the highest performace, boasting an impressive AUC of 0.984. This model outperformed other algorithms in terms of accuracy and sensitivity. Furthermore, when employing a voting mechanism on multi-mass spectrometry data for strain identificaton, the RF model achieved the highest accuracy of 96.67%. The outcomes of this research hold the significant potential for commercial applications, enabling the rapid and precise discrimination of B. longum and B. infantis using MALDI-TOF MS in conjunction with machine learning. Additionally, the approach proposed in this study carries substantial implications across various industries, such as probiotics and pharmaceuticals, where the precise differentiation of specific subspecies is essential for product development and quality control

Characterization of Shiga toxin-producing Escherichia coli isolated from healthy pigs in China

BACKGROUND: Shiga toxin-producing Escherichia coli (STEC) is recognized as an important human diarrheal pathogen. Swine plays an important role as a carrier of this pathogen. In this study we determined the prevalence and characteristics of STEC from healthy swine collected between May 2011 and August 2012 from 3 cities/provinces in China. RESULTS: A total of 1003 samples, including 326 fecal, 351 small intestinal contents and 326 colon contents samples, was analyzed. Two hundred and fifty five samples were stx-positive by PCR and 93 STEC isolates were recovered from 62 stx-positive samples. Twelve O serogroups and 19 O:H serotypes including 6 serotypes (O100:H20/[H20], O143:H38/[H38], O87:H10, O172:H30/[H30], O159:H16, O9:H30/[H30]) rarely found in swine and ruminants were identified. All 93 STEC isolates harbored stx(2) only, all of which were stx(2e) subtype including 1 isolate being a new variant of stx(2e). 53.76%, 15.05% and 2.15% STEC isolates carried astA, hlyA and ehxA respectively. Four STEC isolates harbored the high-pathogenicity island. Of the 15 adherence-associated genes tested, 13 (eae, efa1, iha, lpfA(O113), lpfA(O157/OI-154), lpfA(O157/OI-141), toxB, saa, F4, F5, F6, F17 or F41) were all absent while 2 (paa and F18) were present in 7 and 4 STEC isolates respectively. The majority of the isolates were resistant to tetracycline (79.57%), nalidixic acid (78.49%), trimethoprim-sulfamethoxazole (73.12%) and kanamycin (55.91%). The STEC isolates were divided into 63 pulsed-field gel electrophoresis patterns and 21 sequence types (STs). Isolates of the same STs generally showed the same or similar drug resistance patterns. A higher proportion of STEC isolates from Chongqing showed multidrug resistance with one ST (ST3628) resistant to 14 antimicrobials. CONCLUSIONS: Our results indicate that swine is a significant reservoir of STEC strains in China. Based on comparison by serotypes and sequence types with human strains and presence of virulence genes, the swine STEC may have a low potential to cause human disease

Ultra-Low-Frequency Radio Astronomy Observations from a Selenocentric Orbit: first results of the Longjiang-2 experiment

This paper introduces the first results of observations with the Ultra-Long-Wavelength (ULW) -- Low Frequency Interferometer and Spectrometer (LFIS) on board the selenocentric satellite Longjiang-2. We present a brief description of the satellite and focus on the LFIS payload. The in-orbit commissioning confirmed a reliable operational status of the instrumentation. We also present results of a transition observation, which offers unique measurements on several novel aspects. We estimate the RFI suppression required for such a radio astronomy instrumentation at the Moon distances from Earth to be of the order of 80 dB. We analyse a method of separating Earth- and satellite-originated radio frequency interference (RFI). It is found that the RFI level at frequencies lower than a few MHz is smaller than the receiver noise floor.Comment: Accepted for publication in Experimental Astronomy; 22 pages, 11 figure

Spread of Streptococcus suis Sequence Type 7, China

Streptococcus suis sequence type (ST) 7 has been spreading throughout China. To determine events associated with its emergence, we tested 114 isolates. In all 106 ST7 strains responsible for human outbreaks and sporadic infections, the tetracycline-resistance gene, tetM, was detected on the conjugative transposon Tn916. Horizontal transmission of tetM is suspected

SARS-CoV Infection in a Restaurant from Palm Civet

Contact with food animals was associated with SARS-CoV infection in the People’s Republic of China

Cross-talk between PRMT1-mediated methylation and ubiquitylation on RBM15 controls RNA splicing

RBM15, an RNA binding protein, determines cell-fate specification of many tissues including blood. We demonstrate that RBM15 is methylated by protein arginine methyltransferase 1 (PRMT1) at residue R578 leading to its degradation via ubiquitylation by an E3 ligase (CNOT4). Overexpression of PRMT1 in acute megakaryocytic leukemia cell lines blocks megakaryocyte terminal differentiation by downregulation of RBM15 protein level. Restoring RBM15 protein level rescues megakaryocyte terminal differentiation blocked by PRMT1 overexpression. At the molecular level, RBM15 binds to pre-mRNA intronic regions of genes important for megakaryopoiesis such as GATA1, RUNX1, TAL1 and c-MPL. Furthermore, preferential binding of RBM15 to specific intronic regions recruits the splicing factor SF3B1 to the same sites for alternative splicing. Therefore, PRMT1 regulates alternative RNA splicing via reducing RBM15 protein concentration. Targeting PRMT1 may be a curative therapy to restore megakaryocyte differentiation for acute megakaryocytic leukemia

Identification of target genes of transcription factor activator protein 2 gamma in breast cancer cells

<p>Abstract</p> <p>Background</p> <p>Activator protein 2 gamma (AP-2γ) is a member of the transcription factor activator protein-2 (AP-2) family, which is developmentally regulated and plays a role in human neoplasia. AP-2γ has been found to be overexpressed in most breast cancers, and have a dual role to inhibit tumor initiation and promote tumor progression afterwards during mammary tumorigensis.</p> <p>Methods</p> <p>To identify the gene targets that mediate its effects, we performed chromatin immunoprecipitation (ChIP) to isolate AP-2γ binding sites on genomic DNA from human breast cancer cell line MDA-MB-453.</p> <p>Results</p> <p>20 novel DNA fragments proximal to potential AP-2γ targets were obtained. They are categorized into functional groups of carcinogenesis, metabolism and others. A combination of sequence analysis, reporter gene assays, quantitative real-time PCR, electrophoretic gel mobility shift assays and immunoblot analysis further confirmed the four AP-2γ target genes in carcinogenesis group: ErbB2, CDH2, HPSE and IGSF11. Our results were consistent with the previous reports that ErbB2 was the target gene of AP-2γ. Decreased expression and overexpression of AP-2γ in human breast cancer cells significantly altered the expression of these four genes, indicating that AP-2γ directly regulates them.</p> <p>Conclusion</p> <p>This suggested that AP-2γ can coordinate the expression of a network of genes, involving in carcinogenesis, especially in breast cancer. They could serve as therapeutic targets against breast cancers in the future.</p

The Rhoptry Proteins ROP18 and ROP5 Mediate Toxoplasma gondii Evasion of the Murine, But Not the Human, Interferon-Gamma Response

The obligate intracellular parasite Toxoplasma gondii secretes effector proteins into the host cell that manipulate the immune response allowing it to establish a chronic infection. Crosses between the types I, II and III strains, which are prevalent in North America and Europe, have identified several secreted effectors that determine strain differences in mouse virulence. The polymorphic rhoptry protein kinase ROP18 was recently shown to determine the difference in virulence between type I and III strains by phosphorylating and inactivating the interferon-γ (IFNγ)-induced immunity-related GTPases (IRGs) that promote killing by disrupting the parasitophorous vacuole membrane (PVM) in murine cells. The polymorphic pseudokinase ROP5 determines strain differences in virulence through an unknown mechanism. Here we report that ROP18 can only inhibit accumulation of the IRGs on the PVM of strains that also express virulent ROP5 alleles. In contrast, specific ROP5 alleles can reduce IRG coating even in the absence of ROP18 expression and can directly interact with one or more IRGs. We further show that the allelic combination of ROP18 and ROP5 also determines IRG evasion and virulence of strains belonging to other lineages besides types I, II and III. However, neither ROP18 nor ROP5 markedly affect survival in IFNγ-activated human cells, which lack the multitude of IRGs present in murine cells. These findings suggest that ROP18 and ROP5 have specifically evolved to block the IRGs and are unlikely to have effects in species that do not have the IRG system, such as humans