We present Keck-Adaptive Optics and Hubble Space Telescope high resolution near-infrared (IR) imaging for 500 µm-bright candidate lensing systems identified by the Herschel Multi-tiered Extragalactic Survey (HerMES) and Herschel Astrophysical Terahertz Survey (H-ATLAS). Out of 87 candidates with near-IR imaging, 15 (∼ 17%) display clear near-IR lensing morphologies. We present near-IR lens models to reconstruct and recover basic rest-frame optical morphological properties of the background galaxies from 12 new systems. Sources with the largest near-IR magnification factors also tend to be the most compact, consistent with the size bias predicted from simulations and previous lensing models for sub-millimeter galaxies. For four new sources that also have high-resolution sub-mm maps, we test for differential lensing between the stellar and dust components and find that the 880 µm magnification factor (µ 880 ) is ∼ 1.5 times higher than the near-IR magnification factor (µ NIR ), on average. We also find that the stellar emission is ∼ 2 times more extended in size than dust. The rest-frame optical properties of our sample of Herschel-selected lensed SMGs are consistent with those of unlensed SMGs, which suggests that the two populations are similar. c AB mag 1HerMES S250 J002854.0-420457 HELAISS04 J = 62 × 4 J = 25.8 1HerMES S250 J002906.3-421420 HELAISS01 J = 62 × 4 J = 25.4 1HerMES S250 J003823.7-433705 HELAISS02 J = 125 × 4 J = 25.7 1HerMES S250 J021620.0-032520 HXMM26 Kp = 60 × 30 Kp = 25.6 e 1HerMES S250 J021632.1-053422 HXMM14 J = 125 × 4 J = 25.6 1HerMES S250 J021830.6-053125 HXMM02 J = 177 × 4, Kp = 60 × 18 J = 26.3, Kp = 25.6 e 1HerMES S250 J021836.7-035316 HXMM13 J = 62 × 4 J = 25.6 1HerMES S250 J021942.9-052433 HXMM20 J = 125 × 4 J = 25.6 1HerMES S250 J022016.6-060144 HXMM01 J = 62 × 4, Ks = 80 × 35 J = 25.5, Ks = 25.6 1HerMES S250 J022021.8-015329 HXMM04 J = 62 × 4 J = 25.6 1HerMES S250 J022029.2-064846 HXMM09 J = 62 × 4, H = 120 × 12, K = 80 × 15 J = 25.2, H = 24.8, K = 24.5 1HerMES S250 J022135.2-062618 HXMM03 J = 62 × 4 J = 25.4 1HerMES S250 J022201.7-033340 HXMM11 Ks = 100 × 18 Ks = 25.6 e 1HerMES S250 J022205.5-070727 HXMM23 J = 62 × 4 J = 25.2 1HerMES S250 J022212.9-070224 HXMM28 J = 125 × 4 J = 25.6 1HerMES S250 J022250.8-032414 HXMM22 J = 62 × 4 J = 25.4 1HerMES S250 J022515.3-024707 HXMM19 J = 62 × 4 J = 25.3 1HerMES S250 J022517.5-044610 HXMM27 J = 62 × 4 J = 25.6 1HerMES S250 J022547.9-041750 HXMM05 J = 62 × 4 J = 25.8 1HerMES S250 J023006.0-034153 HXMM12 J = 62 × 4 J = 25.2 1HerMES S250 J032434.4-292646 HECDFS08 J = 62 × 4 J = 25.4 1HerMES S250 J032443.1-282134 HECDFS03 J = 125 × 4 J = 25.4 1HerMES S250 J032636.4-270045 HECDFS05 J = 62 × 4 J = 25.6 1HerMES S250 J032712.7-285106 HECDFS09 J = 62 × 4 J = 25.5 1HerMES S250 J033118.0-272015 HECDFS11 J = 62 × 4 J = 25.3 1HerMES S250 J033210.8-270536 HECDFS04 J = 62 × 4 J = 26.0 1HerMES S250 J033732.5-295353 HECDFS02 J = 177 × 4 J = 26.8 1HerMES S250 J043340.5-540338 HADFS04 J = 62 × 4 J = 25.6 1HerMES S250 J043829.8-541832 HADFS02 J = 62 × 4 J = 25....

New Delhi metallo-β-lactamase-1 (NDM-1) is the most prevalent type of metallo-β-lactamase and hydrolyzes almost all clinically used β-lactam antibiotics. Here we show that the antimicrobial peptide thanatin disrupts the outer membrane of NDM-1-producing bacteria by competitively displacing divalent cations on the outer membrane and inducing the release of lipopolysaccharides. In addition, thanatin inhibits the enzymatic activity of NDM-1 by displacing zinc ions from the active site, and reverses carbapenem resistance in NDM-1-producing bacteria in vitro and in vivo. Thus, thanatin’s dual mechanism of action may be useful for combating infections caused by NDM-1-producing pathogens.

We discuss the rest-frame ultraviolet emission from the starbursting galaxy HFLS3 at a redshift of 6.34. The galaxy was discovered in Herschel/SPIRE data due to its red color in the sub-mm wavelengths from 250 to 500 µm. The apparent instantaneous star-formation rate of HFLS3 inferred from the total far-IR luminosity measured with over 15 photometric data points between 100 and 1000 µm is 2900 M ⊙ yr −1 . Keck/NIRC2 K s -band adaptive optics imaging data showed two potential near-IR counterparts near HFLS3. Previously, the northern galaxy was taken to be in the foreground at z = 2.1 while the southern galaxy was assumed to HFLS3's near-IR counterpart. The recently acquired Hubble/WFC3 and ACS imaging data show conclusively that both optically-bright galaxies are in the foreground at z < 6. A new lensing model based on the Hubble imaging data and the mm-wave continuum emission yields a magnification factor of 2.2 ± 0.3. The lack of multiple imaging constrains the lensing magnification to be lower than either 2.7 or 3.5 at the 95% confidence level for the two scenarios, which attribute one or two components to HFLS3 in the source plane. Once accounting for the possibility of gravitational lensing, the instantaneous star-formation rate is 1320 M ⊙ yr −1 with the 95% confidence lower limit around 830 M ⊙ yr −1 . Using models for the rest-frame UV to far-IR spectral energy distribution (SED) we determine the average star-formation rate over the last 100 Myr to be around 660 M ⊙ yr −1 . The dust and stellar masses of HFLS3 from the same SED models are at the level of 3 × 10 8 M ⊙ and ∼ 5 × 10 10 M ⊙ , respectively, with large systematic uncertainties on assumptions related to the SED model. With Hubble/WFC3 images we also find diffuse near-IR emission about 0.5 arcseconds (∼ 3 kpc) to the South-West of HFLS3 that remains undetected in the ACS imaging data. The emission has a photometric redshift consistent with either z ∼ 6 or a dusty galaxy template at z ∼ 2. If at the same redshift as HFLS3 the detected diffuse emission could be part of the complex merger system that could be triggering the starburst. Alternatively, it could be part of the foreground structure at z ∼ 2.1 that is responsible for lensing of HFLS3.

Cone arrestin (CAR) is a novel member of the arrestin superfamily expressed in retinal cone photoreceptors and the pineal gland. To understand the regulatory mechanisms controlling its cone-and pineal-speci¢c expression, and to facilitate further functional studies using gene knockout approaches, we characterized the genomic organization and the 5P P-£anking region of the mouse CAR (mCAR) gene. The mCAR gene is comprised of 17 exons and 16 introns, encoding ¢ve alternatively spliced transcripts. A 215-bp proximal promoter fragment containing a TATA box, an Sp1 site and four cone-rod homeobox-binding sites is su⁄cient to direct expression in cultured retinoblastoma cells and in cone photoreceptors and the pineal gland in transgenic Xenopus laevis. ß 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.

Rapid and accurate detection of plant pathogens in the field is crucial to prevent the proliferation of infected crops. Polymerase chain reaction (PCR) process is the most reliable and accepted method for plant pathogen diagnosis, however current conventional PCR machines are not portable and require additional post-processing steps to detect the amplified DNA (amplicon) of pathogens. Real-time PCR can directly quantify the amplicon during the DNA amplification without the need for post processing, thus more suitable for field operations, however still takes time and require large instruments that are costly and not portable. Microchip PCR systems have emerged in the past decade to miniaturize conventional PCR systems and to reduce operation time and cost. Real-time microchip PCR systems have also emerged, but unfortunately all reported portable real-time microchip PCR systems require various auxiliary instruments. Here we present a stand-alone real-time microchip PCR system composed of a PCR reaction chamber microchip with integrated thin-film heater, a compact fluorescence detector to detect amplified DNA, a microcontroller to control the entire thermocycling operation with data acquisition capability, and a battery. The entire system is 25×16×8 cm3 in size and 843 g in weight. The disposable microchip requires only 8-µl sample volume and a single PCR run consumes 110 mAh of power. A DNA extraction protocol, notably without the use of liquid nitrogen, chemicals, and other large lab equipment, was developed for field operations. The developed real-time microchip PCR system and the DNA extraction protocol were used to successfully detect six different fungal and bacterial plant pathogens with 100% success rate to a detection limit of 5 ng/8 µl sample.

Aim: To study the intravenous and oral pharmacokinetic behavior of oridonin and its extent of absolute oral bioavailability in rats. Methods: Oridonin was administered to rats via iv (5,10 and 15 mg/kg), po (20,40 and 80 mg/kg) or ip administration (10 mg/kg). The concentrations of oridonin in rat plasma were determined by a high performance liquid chromatography with electrospray ionization mass spec‐trometric detection (HPLC/ESI‐MS) method and the pharmacokinetic parameters were determined by non‐compartmental analysis. Results: The plasma concentration of oridonin after intravenous administration decreased polyexponentially, and the pharmacokinetic parameters of oridonin were dose‐independent within the examined range. Oridonin was absorbed rapidly after oral gavage with a tmax of less than 15 min; the extent of absolute bioavailability of oridonin following oral administration was 4.32%, 4.58% and 10.8%. The extent of absolute bioavailability of oridonin following intraperitoneal administration was 12.6%. Conclusion: First order rate pharmacokinetics were observed for oridonin within the range of iv doses, while the extent of absolute oral bioavailability was rather low and dose‐dependent. The low and dose‐dependent extent of oral bioavailability may be due to the saturation of first‐pass effects.

Given its high resistance, enhanced virulence, and high transmissibility, community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) pneumonia is highly associated with high morbidity and mortality. Anti-virulence therapy is a promising strategy that bypasses the evolutionary pressure on the bacterium to develop resistance. RNAIII-inhibiting peptide (RIP), as an accessory gene regulator (agr)-specific inhibitor, significantly restricts the virulence of S. aureus and protects infected mice from death by blocking the agr quorum sensing system. The protective effects of RIP on the neutropenic mice completely disappeared in a neutrophil-deleted mouse infection model, but not in the macrophage-deleted mice. This result confirmed that the in vivo antibacterial activity of RIP is highly associated with neutrophil function. Phenol-soluble modulins (PSMs), as major leukocyte lysis toxins of CA-MRSA, are directly regulated by the agr system. In this experiment, PSMα1, 2, and 3 significantly induced neutrophil necroptosis by activating mixed lineage kinase-like protein (MLKL) phosphorylation and increasing lactate dehydrogenase release. The S. aureus supernatants harvested from the agr or psmα mutant strains both decreased the phosphorylation level of MLKL and cell lysis. PSMα1-mediated neutrophil lysis was significantly inhibited by necrosulfonamide, necrostatin-1, TNFα antibody, and WRW4. These results showed PSMα1 induced necroptosis depends on formylpeptide receptor 2 (FPR2)-mediated autocrine TNFα. Moreover, the neutrophil necroptosis induced by S. aureus was significantly suppressed and pneumonia was effectively prevented by the blockage of agrA and psmα expression levels. These findings indicate that PSMα-induced necroptosis is a major cause of lung pathology in S. aureus pneumonia and suggest that interfering with the agr quorum sensing signaling pathway is a potential therapeutic strategy.

b Thanatin (THA) displays potent antibiotic activity, especially against extended-spectrum-␤-lactamase (ESBL)-producing Escherichia coli both in vitro and in vivo, with minimal hemolytic toxicity and satisfactory stability in plasma. However, the high cost of thanatin significantly limits its development and clinical application. To reduce the cost of peptide synthesis, a formulation of cyclic thanatin (C-thanatin) called linear thanatin (L-thanatin) was synthesized and its activity was evaluated in vivo and in vitro. Results showed that C-thanatin and L-thanatin MICs did not differ against eight Gram-negative and two Gram-positive bacterial strains. Furthermore, the survival rates of ESBL-producing-E. coli-infected mice were consistent after C-thanatin or L-thanatin treatment at 5 or 10 mg/kg of body weight. Neither C-thanatin nor L-thanatin showed toxicity for human red blood cells (hRBCs) and human umbilical vein endothelial cells (HUVECs) at a concentration as high as 256 g/ml. Results of circular dichroism spectroscopy indicated that the secondary structure of L-thanatin is extremely similar to that of C-thanatin. Membrane permeabilization and depolarization assays showed that C-thanatin and L-thanatin have similar abilities to permeabilize the outer and inner membranes and to induce membrane depolarization in ESBL-producing E. coli. However, neither of them caused significant HUVEC membrane permeability. These findings indicate that the two peptides have similar effects on bacterial cell membranes and that the disulfide bond in thanatin is not essential for its antimicrobial activities in vivo and in vitro. L-thanatin is thus a promising low-cost peptide candidate for treating ESBL-producing E. coli infections. T hanatin (THA) is a cationic antimicrobial peptide that was first discovered in the hemipteran insect Podisus maculiventris.This peptide is composed of 21 amino acids (GSKKPVPIIYCNR RTGKCQRM), with an intramolecular disulfide bridge between the two cysteines at positions 11 and 18. Our previous studies revealed that thanatin exhibits potent antibiotic activity, especially against extended-spectrum-␤-lactamase (ESBL)-producing Esc herichia coli, both in vitro and in vivo, with a low inherent ability to induce microbial resistance, minimal hemolytic toxicity, and high stability in plasma (1, 2).Despite their promise for clinical benefit, the high cost of producing peptide drugs such as thanatin significantly limits their development and clinical application. Compared with conventional antibiotics, the costs of cationic antimicrobial peptides are always prohibitively high for large-scale production (3). Intrachain disulfide bonds exist in many naturally occurring peptides and play important roles in biological activities. However, synthesis of peptide drugs with one or more disulfide bridges is complicated and expensive (4).Previous studies found that the disulfide bonds of protegrin-1 are not essential for its antimicrobial and hemolytic activities in vitro (5). To reduce the cost of thanatin synthes...