Separating crystal nucleation and growth processes is key to controlling crystal dimensions

Scientists are seeking ways to make beneficial but elusive sugars found in breast milk

To learn more about lava’s unpredictable behavior and to mitigate its damage, scientists are creating and manipulating their own molten rock

Actor Madirakshi Mundle on playing Sita in “Siya Ke Ram”

Hayden Library - TA418.9.N35 F87 2018

Before this, David and his wife Candice were seen grooving to recent Telugu hit track Butta Bomma from Allu Arjun starrer Ala Vaikuntapuramlo.

1. Three youths die from syndrome possibly linked to COVID-19  The Age
2. Kawasaki disease: Children die in New York from coronavirus-linked syndrome  NEWS.com.au
3. Three children in New York die from illness feared linked to coronavirus  ABC News
4. New York looking further into emerging COVID-19 issue affecting children  The Daily News Online
5. 5-year-old dies from severe illness linked to coronavirus  msnNOW
6. View Full coverage on Google News

Actinobacillus pleuropneumoniae (App) is the etiological agent of acute porcine pneumonia and responsible for severe economic losses worldwide. The capsule polymer of App serotype 1 (App1) consists of [4)-GlcNAc-β(1,6)-Gal-α-1-(PO4-] repeating units that are O-acetylated at O-6 of the GlcNAc. It is a major virulence factor and was used in previous studies in the successful generation of an experimental glycoconjugate vaccine. However, the application of glycoconjugate vaccines in the animal health sector is limited, presumably because of the high costs associated with harvesting the polymer from pathogen culture. Consequently, here we exploited the capsule polymerase Cps1B of App1 as an in vitro synthesis tool and an alternative for capsule polymer provision. Cps1B consists of two catalytic domains, as well as a domain rich in tetratricopeptide repeats (TPRs). We compared the elongation mechanism of Cps1B with that of a ΔTPR truncation (Cps1B-ΔTPR). Interestingly, the product profiles displayed by Cps1B suggested processive elongation of the nascent polymer, whereas Cps1B-ΔTPR appeared to work in a more distributive manner. The dispersity of the synthesized products could be reduced by generating single-action transferases and immobilizing them on individual columns, separating the two catalytic activities. Furthermore, we identified the O-acetyltransferase Cps1D of App1 and used it to modify the polymers produced by Cps1B. Two-dimensional NMR analyses of the products revealed O-acetylation levels identical to those of polymer harvested from App1 culture supernatants. In conclusion, we have established a protocol for the pathogen-free in vitro synthesis of tailored, nature-identical App1 capsule polymers.

The dextransucrase DSR-OK from the Gram-positive bacterium Oenococcus kitaharae DSM17330 produces a dextran of the highest molar mass reported to date (∼109 g/mol). In this study, we selected a recombinant form, DSR-OKΔ1, to identify molecular determinants involved in the sugar polymerization mechanism and that confer its ability to produce a very-high-molar-mass polymer. In domain V of DSR-OK, we identified seven putative sugar-binding pockets characteristic of glycoside hydrolase 70 (GH70) glucansucrases that are known to be involved in glucan binding. We investigated their role in polymer synthesis through several approaches, including monitoring of dextran synthesis, affinity assays, sugar binding pocket deletions, site-directed mutagenesis, and construction of chimeric enzymes. Substitution of only two stacking aromatic residues in two consecutive sugar-binding pockets (variant DSR-OKΔ1-Y1162A-F1228A) induced quasi-complete loss of very-high-molar-mass dextran synthesis, resulting in production of only 10–13 kg/mol polymers. Moreover, the double mutation completely switched the semiprocessive mode of DSR-OKΔ1 toward a distributive one, highlighting the strong influence of these pockets on enzyme processivity. Finally, the position of each pocket relative to the active site also appeared to be important for polymer elongation. We propose that sugar-binding pockets spatially closer to the catalytic domain play a major role in the control of processivity. A deep structural characterization, if possible with large-molar-mass sugar ligands, would allow confirming this hypothesis.

Bacterial biofilms are cellular communities that produce an adherent matrix. Exopolysaccharides are key structural components of this matrix and are required for the assembly and architecture of biofilms produced by a wide variety of microorganisms. The human bacterial pathogens Escherichia coli and Salmonella enterica produce a biofilm matrix composed primarily of the exopolysaccharide phosphoethanolamine (pEtN) cellulose. Once thought to be composed of only underivatized cellulose, the pEtN modification present in these matrices has been implicated in the overall architecture and integrity of the biofilm. However, an understanding of the mechanism underlying pEtN derivatization of the cellulose exopolysaccharide remains elusive. The bacterial cellulose synthase subunit G (BcsG) is a predicted inner membrane–localized metalloenzyme that has been proposed to catalyze the transfer of the pEtN group from membrane phospholipids to cellulose. Here we present evidence that the C-terminal domain of BcsG from E. coli (EcBcsGΔN) functions as a phosphoethanolamine transferase in vitro with substrate preference for cellulosic materials. Structural characterization of EcBcsGΔN revealed that it belongs to the alkaline phosphatase superfamily, contains a Zn2+ ion at its active center, and is structurally similar to characterized enzymes that confer colistin resistance in Gram-negative bacteria. Informed by our structural studies, we present a functional complementation experiment in E. coli AR3110, indicating that the activity of the BcsG C-terminal domain is essential for integrity of the pellicular biofilm. Furthermore, our results established a similar but distinct active-site architecture and catalytic mechanism shared between BcsG and the colistin resistance enzymes.

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.

A new imaging technique may give researchers fresh insights into brain development, function, and disease

The human brain is often said to be the most complex object in the known universe, and there’s good reason to believe that it is. That lump of jelly inside your head contains at least 80 billion nerve cells, or neurons, and even more of the non-neuronal cells called glia. Between them, they form hundreds of trillions of precise synaptic connections; but they all have moveable parts, and these connections can change. Neurons can extend and retract their delicate fibres; some types of glial cells can crawl through the brain; and neurons and glia routinely work together to create new connections and eliminate old ones.

These processes begin before we are born, and occur until we die, making the brain a highly dynamic organ that undergoes continuous change throughout life. At any given moment, many millions of them are being modified in one way or another, to reshape the brain’s circuitry in response to our daily experiences. Researchers at Yale University have now developed an imaging technique that enables them to visualise the density of synapses in the living human brain, and offers a promising new way of studying how the organ develops and functions, and also how it deteriorates in various neurological and psychiatric conditions.

Related: Brain’s immune cells hyperactive in schizophrenia

Related: 3D model of a nerve terminal in atomic detail | Mo Costandi

New research provides evidence for the idea that sleep restores cellular homeostasis in the brain and helps us to forget irrelevant information

We spend one third of our lives sleeping, but we still do not know exactly why we sleep. Recent research shows that that the brain does its housekeeping while we sleep, and clears away its waste. According to another hypothesis, sleep plays the vital role of restoring the right balance of brain synapses to enhance learning, and two studies published in today’s issue of Science now provide the most direct evidence yet for this idea.

We do know that sleep is important for consolidating newly formed memories. During waking hours, we learn all kinds of new information, both consciously and unconsciously. To store it, the brain modifies large numbers of synaptic connections, making some of them stronger and larger, and it’s now thought that as we sleep other synapses are weakened or destroyed, so that the important new information is stored for later use, while irrelevant material, which could interfere with learning, is not.

Related: The Homer Simpson effect: forgetting to remember

Related: How to optimise your brain's waste disposal system

David Warner, dressed in his SRH kit with a bat in hand, delivered the dialogue with much gusto and asked his fans to guess the movie.

A focus on customer enablement across all Cadence sub-organizations has led to a cross-functional effort to identify opportunities to bring our customers to proficiency with our products and flows. Hence, Rapid Adoption Kits -- RAKs -- for Synthesis...(read more)

There exists an unauthenticated SEH based vulnerability in the HTTP server of Sync Breeze Enterprise version 10.1.16, when sending a GET request with an excessive length it is possible for a malicious user to overwrite the SEH record and execute a payload that would run under the Windows NT AUTHORITYSYSTEM account. The SEH record is overwritten with a "POP,POP,RET" pointer from the application library libspp.dll. This exploit has been successfully tested on Windows XP, 7 and 10 (x86->x64). It should work against all versions of Windows and service packs.

Three children in New York have died from a rare inflammatory syndrome believed to be linked to the novel coronavirus, Governor Andrew Cuomo said on Saturday, a development that may augur a pandemic risk for the very young.Both Cuomo and his counterpart in the neighbouring state of New Jersey also spoke on Saturday about the pandemic’s growing toll on mental health, another factor on the minds of governors as they weigh the impact of mounting job losses against health risks in moving to loosen…

Three children in New York have died from a rare inflammatory syndrome believed to be linked to the novel coronavirus, Governor Andrew Cuomo said on Saturday, a development that may augur a pandemic risk for the very young.

Three children in New York have died from a rare inflammatory syndrome believed to be linked to the novel coronavirus, Governor Andrew Cuomo said on Saturday, adding that the state is working with the CDC to investigate the syndrome. Jillian Kitchener has more.

Three children in New York have died from a rare inflammatory syndrome believed to be linked to the novel coronavirus, Governor Andrew Cuomo said on Saturday, a development that may augur a pandemic risk for the very young.

Three children in New York have died from a rare inflammatory syndrome believed to be linked to the novel coronavirus, Governor Andrew Cuomo said on Saturday, a development that may augur a pandemic risk for the very young.

This note identifies key findings and policy messages on how small and medium- sized enterprises (SMEs) in Southeast Asia can enhance integration in global value chains (GVCs). The list of policy messages in this note is not intended to be exhaustive but rather to provide a set of concrete and actionable measures.

Developing countries are disproportionately affected by the rising trend of losses from climate-related extreme events. This paper uses case studies of Colombia and Senegal to examine how countries are using financial protection as part of their approaches to managing climate risks; it also identifies emerging priorities for development co-operation providers in supporting financial protection against climate risks.

How can assessment and evaluation policies work together more effectively to improve student outcomes in primary and secondary schools? This report provides an international comparative analysis and policy advice to countries on how evaluation and assessment arrangements can be embedded within a consistent framework to improve the quality, equity and efficiency of school education.