Morrisons has taken the precautionary step of recalling Market Street Living Herbs because the products might contain Listeria monocytogenes.

Unilever is recalling Wall’s Mini Calippo (Orange and Lemon-Lime) multi-packs because they may contain small pieces of metal. The presence of metal makes this product unsafe to eat.

Purdue basketball faces Virginia in the Elite Eight

A first half deficit proved too much to handle for the Boilermakers. Purdue also lost Elijah Sindelar and Rondale Moore to injury in the first half.

Purdue Boilermakers play seven games in West Lafayette during the 2018 season, including their first four

After leaning on their defense in 2017, the Boilermakers will need more from their offense in coach Jeff Brohm's second season

Prior to joining the Boilermakers, Elliott Cribby served as pitching coach and recruiting coordinator at Seattle University.

Journal & Courier sports editor Ken Thompson makes his choices of which Purdue football players wore Nos. 1 through 5 the best. Who would you choose?

Vincent Edwards signed with the Houston Rockets on Thursday, per the team.

Brandon Newman's stock rose considerably in the past six months. The 2019 guard from Valparaiso will play at Montverde (Florida) Academy as a senior.

Carsen Edwards led Purdue in scoring last season and was named an All-American.

Purdue coach Matt Painter and staff will explore the July evaluation period over the next three weeks. But the recruiting foundation for 2019 is set.

Games involving Notre Dame, Purdue and Indiana could have a lot at stake this season.

The Red Devil linebacker will join the Boilermakers in the fall.

The Boilermakers open the 2018 ESPN Charleston Classic against Appalachian State, with the winner facing Davidson or Wichita State.

A look at where locals land on new national lists

Top 10 scorers in Purdue men's basketball history

Now you can read all of IndyStar's sports content in one place with our free INSports app.

From Notre Dame to the Monon Bell. We rank Indiana's top 50 college football games in 2018.

Caleb Swanigan's 21 points and 16 rebounds led Portland to a semifinal victory over Memphis.

Tracking the Boilermakers throughout the offseason

Indianapolis police arrested a man on Saturday near the location of the fatal police shooting of Dreasjon "Sean" Reed days earlier.

Dennis Barrett, an east Indianapolis native, died of the coronavirus in March. His wife remembers him as a devoted father and ambitious entrepreneur.

Demonstrators describe an arrest and pepper ball use by IMPD during a protest over the death of Dreasjon Reed near 62nd Street and Michigan Road.

Indianapolis police arrested a man on Saturday near the location of the fatal police shooting of Dreasjon "Sean" Reed days earlier.

Emacs "predates Linux, and was once far more popular," writes LWN.net, while adding that the text editor "has fallen into relative obscurity over the years." Then it reports on a "mega-thread" on the emacs-devel mailing list about how to make Emacs more appealing and attractive to users: The discussion started with a post from "ndame" asking why Emacs is "so square"; the appearance of things like buttons could be improved with rounded corners, they said. Richard Stallman, one of the original authors of Emacs, seemed somewhat dismissive in his reply: "Perhaps we should implement a mode that puts cosmetics on Emacs so it will appeal to those who judge by the surface of things." But Stefan Kangas thought there was more to it than that: I think it's unfortunate if we assume that this is all bells and whistles. Graphical design elements can also improve usability. I also don't know that it's helpful to assume that the rest of the world will take the enlightened stance.... He wondered if there was "any reason not to improve the default look". Stallman said that there are some technical barriers in finding someone interested in and capable of doing the work needed, but there is an overarching problem that needs to be addressed first: The code to interface Emacs to X-based GUIs needs rewriting by an expert, and has needed it for decades. Until it gets that rewrite, changes in it are likely to break something. Stallman did agree that the graphical design could improve usability, "but I have a feeling that the changes that would help are deeper issues than the shape of corners". It was a long and interesting discussion, touching on the popularity of both Vim and Visual Studio Code, while another post questioned whether Emacs should even be prioritizing its menu bar and tool bar. One post suggested "starter kits" to make the text editor more friendly to newcomers, another suggested making Cntrl-C cut-and-paste the default key binding, and one asked whether it was Emacs' terminology and keyboard shortcuts that might be confusing to users coming from Microsoft Word. "You are basically making a commitment to being or becoming a power user..." argued another post. "If you just want to do 'casual' text editing emacs is a very weird choice in 2020."

Read more of this story at Slashdot.

Zookeepers are sharing a new challenge to help lift their spirits during the coronavirus lockdown.

In the latest MOTD podcast the experts discussed the top 10 Ballon d'Or winners of the Premier League era - and here's how you ranked them.

Kingston’s top health officials say that there are no current cases of COVID-19 active in the city.

Dynamo Dresden, who play in the second tier of German Football, have put their entire squad and coaching staff into two-week isolation after recording two new coronavirus cases.

More than 70 public figures sign an open letter to the prime minister calling for more transparency.

Ultimately, there are no easy solutions to reigniting a Covid-19 affected economy. It is evident, however, that addressing the public health crisis is non-negotiable, writes Haroon Bhorat.

A Canadian department store chain is calling it quits after more than a century in business.

Frank Soo, the first and only player of Asian heritage to represent England's national football team, has been honoured by Google.

The city says couples can book its Helena Gutteridge Plaza at City Hall for just $85 and bring eight guests to have an outdoor, physically distant wedding ceremony.

6 September 2013

12 November 2014 , Volume 90, Number 6

Members Event

Event participants

Professor Joseph S Nye, University Distinguished Service Professor, Harvard Kennedy School of Government
Chair: Gideon Rachman, Chief Foreign Affairs Commentator, Financial Times

The government said it's distributing the promising coronavirus drug, remdesivir, to some hard-hit states. Eventually, all 50 states should get it.

Antibodies are widely used as cancer therapeutics, but their current use is limited by the low number of antigens restricted to cancer cells. A receptor tyrosine kinase, receptor tyrosine kinase-like orphan receptor 2 (ROR2), is normally expressed only during embryogenesis and is tightly down-regulated in postnatal healthy tissues. However, it is up-regulated in a diverse set of hematologic and solid malignancies, thus ROR2 represents a candidate antigen for antibody-based cancer therapy. Here we describe the affinity maturation and humanization of a rabbit mAb that binds human and mouse ROR2 but not human ROR1 or other human cell-surface antigens. Co-crystallization of the parental rabbit mAb in complex with the human ROR2 kringle domain (hROR2-Kr) guided affinity maturation by heavy-chain complementarity-determining region 3 (HCDR3)-focused mutagenesis and selection. The affinity-matured rabbit mAb was then humanized by complementarity-determining region (CDR) grafting and framework fine tuning and again co-crystallized with hROR2-Kr. We show that the affinity-matured and humanized mAb retains strong affinity and specificity to ROR2 and, following conversion to a T cell–engaging bispecific antibody, has potent cytotoxicity toward ROR2-expressing cells. We anticipate that this humanized affinity-matured mAb will find application for antibody-based cancer therapy of ROR2-expressing neoplasms.

Extracytoplasmic sugar decoration of glycopolymer components of the bacterial cell wall contributes to their structural diversity. Typically, the molecular mechanism that underpins such a decoration process involves a three-component glycosylation system (TGS) represented by an undecaprenyl-phosphate (Und-P) sugar-activating glycosyltransferase (Und-P GT), a flippase, and a polytopic glycosyltransferase (PolM GT) dedicated to attaching sugar residues to a specific glycopolymer. Here, using bioinformatic analyses, CRISPR-assisted recombineering, structural analysis of cell wall–associated polysaccharides (CWPS) through MALDI-TOF MS and methylation analysis, we report on three such systems in the bacterium Lactococcus lactis. On the basis of sequence similarities, we first identified three gene pairs, csdAB, csdCD, and csdEF, each encoding an Und-P GT and a PolM GT, as potential TGS component candidates. Our experimental results show that csdAB and csdCD are involved in Glc side-chain addition on the CWPS components rhamnan and polysaccharide pellicle (PSP), respectively, whereas csdEF plays a role in galactosylation of lipoteichoic acid (LTA). We also identified a potential flippase encoded in the L. lactis genome (llnz_02975, cflA) and confirmed that it participates in the glycosylation of the three cell wall glycopolymers rhamnan, PSP, and LTA, thus indicating that its function is shared by the three TGSs. Finally, we observed that glucosylation of both rhamnan and PSP can increase resistance to bacteriophage predation and that LTA galactosylation alters L. lactis resistance to bacteriocin.

β-1,3-d-Glucan is a ubiquitous glucose polymer produced by plants, bacteria, and most fungi. It has been used as a diagnostic tool in patients with invasive mycoses via a highly-sensitive reagent consisting of the blood coagulation system of horseshoe crab. However, no method is currently available for measuring β-1,6-glucan, another primary β-glucan structure of fungal polysaccharides. Herein, we describe the development of an economical and highly-sensitive and specific assay for β-1,6-glucan using a modified recombinant endo-β-1,6-glucanase having diminished glucan hydrolase activity. The purified β-1,6-glucanase derivative bound to the β-1,6-glucan pustulan with a KD of 16.4 nm. We validated the specificity of this β-1,6-glucan probe by demonstrating its ability to detect cell wall β-1,6-glucan from both yeast and hyphal forms of the opportunistic fungal pathogen Candida albicans, without any detectable binding to glucan lacking the long β-1,6-glucan branch. We developed a sandwich ELISA-like assay with a low limit of quantification for pustulan (1.5 pg/ml), and we successfully employed this assay in the quantification of extracellular β-1,6-glucan released by >250 patient-derived strains of different Candida species (including Candida auris) in culture supernatant in vitro. We also used this assay to measure β-1,6-glucan in vivo in the serum and in several organs in a mouse model of systemic candidiasis. Our work describes a reliable method for β-1,6-glucan detection, which may prove useful for the diagnosis of invasive fungal infections.

Lens proteins become increasingly cross-linked through nondisulfide linkages during aging and cataract formation. One mechanism that has been implicated in this cross-linking is glycation through formation of advanced glycation end products (AGEs). Here, we found an age-associated increase in stiffness in human lenses that was directly correlated with levels of protein–cross-linking AGEs. α-Crystallin in the lens binds to other proteins and prevents their denaturation and aggregation through its chaperone-like activity. Using a FRET-based assay, we examined the stability of the αA-crystallin–γD-crystallin complex for up to 12 days and observed that this complex is stable in PBS and upon incubation with human lens–epithelial cell lysate or lens homogenate. Addition of 2 mm ATP to the lysate or homogenate did not decrease the stability of the complex. We also generated complexes of human αA-crystallin or αB-crystallin with alcohol dehydrogenase or citrate synthase by applying thermal stress. Upon glycation under physiological conditions, the chaperone–client complexes underwent greater extents of cross-linking than did uncomplexed protein mixtures. LC-MS/MS analyses revealed that the levels of cross-linking AGEs were significantly higher in the glycated chaperone–client complexes than in glycated but uncomplexed protein mixtures. Mouse lenses subjected to thermal stress followed by glycation lost resilience more extensively than lenses subjected to thermal stress or glycation alone, and this loss was accompanied by higher protein cross-linking and higher cross-linking AGE levels. These results uncover a protein cross-linking mechanism in the lens and suggest that AGE-mediated cross-linking of α-crystallin–client complexes could contribute to lens aging and presbyopia.

Multidrug resistance (MDR) in cancer arises from cross-resistance to structurally- and functionally-divergent chemotherapeutic drugs. In particular, MDR is characterized by increased expression and activity of ATP-binding cassette (ABC) superfamily transporters. Sphingolipids are substrates of ABC proteins in cell signaling, membrane biosynthesis, and inflammation, for example, and their products can favor cancer progression. Glucosylceramide (GlcCer) is a ubiquitous glycosphingolipid (GSL) generated by glucosylceramide synthase, a key regulatory enzyme encoded by the UDP-glucose ceramide glucosyltransferase (UGCG) gene. Stressed cells increase de novo biosynthesis of ceramides, which return to sub-toxic levels after UGCG mediates incorporation into GlcCer. Given that cancer cells seem to mobilize UGCG and have increased GSL content for ceramide clearance, which ultimately contributes to chemotherapy failure, here we investigated how inhibition of GSL biosynthesis affects the MDR phenotype of chronic myeloid leukemias. We found that MDR is associated with higher UGCG expression and with a complex GSL profile. UGCG inhibition with the ceramide analog d-threo-1-(3,4,-ethylenedioxy)phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol (EtDO-P4) greatly reduced GSL and monosialotetrahexosylganglioside levels, and co-treatment with standard chemotherapeutics sensitized cells to mitochondrial membrane potential loss and apoptosis. ABC subfamily B member 1 (ABCB1) expression was reduced, and ABCC-mediated efflux activity was modulated by competition with nonglycosylated ceramides. Consistently, inhibition of ABCC-mediated transport reduced the efflux of exogenous C6-ceramide. Overall, UGCG inhibition impaired the malignant glycophenotype of MDR leukemias, which typically overcomes drug resistance through distinct mechanisms. This work sheds light on the involvement of GSL in chemotherapy failure, and its findings suggest that targeted GSL modulation could help manage MDR leukemias.