The intracellular pathogen Mycobacterium tuberculosis (Mtb) causes tuberculosis. Enhanced intracellular survival (Eis) protein, secreted by Mtb, enhances survival of Mycobacterium smegmatis (Msm) in macrophages. Mtb Eis was shown to suppress host immune defenses by negatively modulating autophagy, inflammation, and cell death through JNK-dependent inhibition of reactive oxygen species (ROS) generation. Mtb Eis was recently demonstrated to contribute to drug resistance by acetylating multiple amines of aminoglycosides. However, the mechanism of enhanced intracellular survival by Mtb Eis remains unanswered. Therefore, we have characterized both Mtb and Msm Eis proteins biochemically and structurally. We have discovered that Mtb Eis is an efficient N ɛ -acetyltransferase, rapidly acetylating Lys55 of dualspecificity protein phosphatase 16 (DUSP16)/mitogen-activated protein kinase phosphatase-7 (MKP-7), a JNK-specific phosphatase. In contrast, Msm Eis is more efficient as an N α -acetyltransferase. We also show that Msm Eis acetylates aminoglycosides as readily as Mtb Eis. Furthermore, Mtb Eis, but not Msm Eis, inhibits LPSinduced JNK phosphorylation. This functional difference against DUSP16/MKP-7 can be understood by comparing the structures of two Eis proteins. The active site of Mtb Eis with a narrow channel seems more suitable for sequence-specific recognition of the protein substrate than the pocket-shaped active site of Msm Eis. We propose that Mtb Eis initiates the inhibition of JNK-dependent autophagy, phagosome maturation, and ROS generation by acetylating DUSP16/MKP-7. Our work thus provides insight into the mechanism of suppressing host immune responses and enhancing mycobacterial survival within macrophages by Mtb Eis.Rv2416c | lysine acetylation | antituberculosis drug N early one-third of the world's population is infected with Mycobacterium tuberculosis (Mtb). This pathogenic bacterium causes tuberculosis, which claims the lives of millions of people every year (1). Tuberculosis has also become a global health issue owing to the increased incidences of multidrug-resistant and extensively drug-resistant strains of Mtb (2). This makes a search for targets of new antituberculosis drugs urgent. Mtb is a highly successful human pathogen, surviving and multiplying within the human macrophage cells of the infected people (3). Therefore, treatment of tuberculosis is difficult, requiring many months of taking a combination of antibiotics. Mtb has the ability to persist in the form of a long-term asymptomatic infection, referred to as latent tuberculosis (4). Latent tuberculosis becomes activated when the body's immune system is weakened. As a result, tuberculosis is the major cause of death among immuno-compromised AIDS patients (5).In mycobacterial infection, host innate immune responses may play a crucial role in early protection against Mtb infection, leading to establishment of effective adaptive immunity to tuberculosis (6). Additionally, MAPK pathways are activated by Mtb or its components and play an e...

Most prior studies of primary diagnosis in surgical pathology using whole slide imaging (WSI) versus microscopy have focused on specific organ systems or included relatively few cases. The objective of this study was to demonstrate that WSI is noninferior to microscopy for primary diagnosis in surgical pathology. A blinded randomized noninferiority study was conducted across the entire range of surgical pathology cases (biopsies and resections, including hematoxylin and eosin, immunohistochemistry, and special stains) from 4 institutions using the original sign-out diagnosis (baseline diagnosis) as the reference standard. Cases were scanned, converted to WSI and randomized. Sixteen pathologists interpreted cases by microscopy or WSI, followed by a wash-out period of ≥4 weeks, after which cases were read by the same observers using the other modality. Major discordances were identified by an adjudication panel, and the differences between major discordance rates for both microscopy (against the reference standard) and WSI (against the reference standard) were calculated. A total of 1992 cases were included, resulting in 15,925 reads. The major discordance rate with the reference standard diagnosis was 4.9% for WSI and 4.6% for microscopy. The difference between major discordance rates for microscopy and WSI was 0.4% (95% confidence interval, −0.30% to 1.01%). The difference in major discordance rates for WSI and microscopy was highest in endocrine pathology (1.8%), neoplastic kidney pathology (1.5%), urinary bladder pathology (1.3%), and gynecologic pathology (1.2%). Detailed analysis of these cases revealed no instances where interpretation by WSI was consistently inaccurate compared with microscopy for multiple observers. We conclude that WSI is noninferior to microscopy for primary diagnosis in surgical pathology, including biopsies and resections stained with hematoxylin and eosin, immunohistochemistry and special stains. This conclusion is valid across a wide variety of organ systems and specimen types.

We studied the role of methyl jasmonate (MeJA) in alleviating NaCl-induced salt stress on soybean growth and development in hydroponics medium. Soybean seedlings were exposed to 60 mM NaCl stress for 2 weeks, 24 h after the application of 20 and 30 µM MeJA. NaCl stress induced a significant reduction in plant growth, endogenous bioactive gibberellin (GA4), photosynthesis and transpiration rate, while a marked increase in the endogenous abscisic acid (ABA) and proline contents were recorded. MeJA application greatly mitigated the adverse effects of NaCl on soybean growth and endogenous hormones. MeJA significantly increased ABA levels, while the endogenous amount of GA4 was reduced by the application of NaCl. Our study revealed that MeJA counteracted the negative effects of NaCl stress on plant growth, chlorophyll content, leaf photosynthetic rate, leaf transpiration rate, and proline content.

The crystal structure of M. tuberculosis l,d-transpeptidase (LdtMt2; Rv2518c) has been determined in both ligand-free and meropenem-bound forms. The detailed view of the interactions between meropenem and LdtMt2 will be useful in structure-guided discovery of new antituberculosis drugs.

Silicon (Si) is abundant in the soil, yet its role in plant biology has been poorly understood. The role of Si in soybean growth and its effectiveness in salt stress alleviation was investigated. Sodium metasilicate (Na 2 SiO 3 ) was given as Si source to hydroponically grown soybean (Glycine max (L.) Merr.). The plant growth attributes, i.e. plant height, plant fresh and dry biomass, chlorophyll contents and endogenous gibberellins (GAs) level improved with 2.5 mM Si, while endogenous abscisic acid (ABA) and free proline contents were not affected as compared to control. Sodium chloride (NaCl) significantly decreased growth attributes and endogenous gibberellins levels but markedly enhanced ABA and proline contents of soybean leaves. An addition of Si to salt stressed plants substantially alleviated the adverse effects of NaCl on growth, as it enhanced endogenous gibberellins, while reduced the levels of ABA and proline. GAs analysis of soybean leaves also showed that both early C13 hydroxylation and non C13 hydroxylation pathways of gibberellin biosynthesis were operating in soybean. The major GA biosynthesis pathway was identified as non C13 hydroxylation, which led to the formation of bioactive GA 4 . Current study suggests that Si application alleviates the detrimental effect of salinity stress on growth and development of soybean.