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High-throughput and site-specific N-glycosylation analysis of human alpha-1-acid glycoprotein offers a great potential for new biomarker discovery

Toma Keser
Dec 29, 2020; 0:RA120.002433v1-mcp.RA120.002433
Research




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Protein modification characteristics of the malaria parasite Plasmodium falciparum and the infected erythrocytes

Jianhua Wang
Nov 4, 2020; 0:RA120.002375v1-mcp.RA120.002375
Research




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Site-specific contacts enable distinct modes of TRPV1 regulation by the potassium channel Kv{beta}1 subunit [Molecular Biophysics]

Transient receptor potential vanilloid 1 (TRPV1) channel is a multimodal receptor that is responsible for nociceptive, thermal, and mechanical sensations. However, which biomolecular partners specifically interact with TRPV1 remains to be elucidated. Here, we used cDNA library screening of genes from mouse dorsal root ganglia combined with patch-clamp electrophysiology to identify the voltage-gated potassium channel auxiliary subunit Kvβ1 physically interacting with TRPV1 channel and regulating its function. The interaction was validated in situ using endogenous dorsal root ganglia neurons, as well as a recombinant expression model in HEK 293T cells. The presence of Kvβ1 enhanced the expression stability of TRPV1 channels on the plasma membrane and the nociceptive current density. Surprisingly, Kvβ1 interaction also shifted the temperature threshold for TRPV1 thermal activation. Using site-specific mapping, we further revealed that Kvβ1 interacted with the membrane-distal domain and membrane-proximal domain of TRPV1 to regulate its membrane expression and temperature-activation threshold, respectively. Our data therefore suggest that Kvβ1 is a key element in the TRPV1 signaling complex and exerts dual regulatory effects in a site-specific manner.




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High resolution structure of human apolipoprotein (a) kringle IV type 2: beyond the lysine binding site

Alice Santonastaso
Dec 1, 2020; 61:1687-1696
Research Articles




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Mass spectrometry characterization of light chain fragmentation sites in cardiac AL amyloidosis: insights into the timing of proteolysis [Genomics and Proteomics]

Amyloid fibrils are polymeric structures originating from aggregation of misfolded proteins. In vivo, proteolysis may modulate amyloidogenesis and fibril stability. In light chain (AL) amyloidosis, fragmented light chains (LCs) are abundant components of amyloid deposits; however, site and timing of proteolysis are debated. Identification of the N and C termini of LC fragments is instrumental to understanding involved processes and enzymes. We investigated the N and C terminome of the LC proteoforms in fibrils extracted from the hearts of two AL cardiomyopathy patients, using a proteomic approach based on derivatization of N- and C-terminal residues, followed by mapping of fragmentation sites on the structures of native and fibrillar relevant LCs. We provide the first high-specificity map of proteolytic cleavages in natural AL amyloid. Proteolysis occurs both on the LC variable and constant domains, generating a complex fragmentation pattern. The structural analysis indicates extensive remodeling by multiple proteases, largely taking place on poorly folded regions of the fibril surfaces. This study adds novel important knowledge on amyloid LC processing: although our data do not exclude that proteolysis of native LC dimers may destabilize their structure and favor fibril formation, the data show that LC deposition largely precedes the proteolytic events documentable in mature AL fibrils.




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Generation and characterization of LPA-KIV9, a murine monoclonal antibody binding a single site on apolipoprotein (a) [Research Articles]

Lipoprotein (a) [Lp(a)] is a risk factor for CVD and a target of therapy, but Lp(a) measurements are not globally standardized. Commercially available assays generally use polyclonal antibodies that detect multiple sites within the kringle (K)IV2 repeat region of Lp(a) and may lead to inaccurate assessments of plasma levels. With increasing awareness of Lp(a) as a cardiovascular risk factor and the active clinical development of new potential therapeutic approaches, the broad availability of reagents capable of providing isoform independence of Lp(a) measurements is paramount. To address this issue, we generated a murine monoclonal antibody that binds to only one site on apo(a). A BALB/C mouse was immunized with a truncated version of apo(a) that contained eight total KIV repeats, including only one copy of KIV2. We generated hybridomas, screened them, and successfully produced a KIV2-independent monoclonal antibody, named LPA-KIV9. Using a variety of truncated apo(a) constructs to map its binding site, we found that LPA-KIV9 binds to KIV9 without binding to plasminogen. Fine peptide mapping revealed that LPA-KIV9 bound to the sequence 4076LETPTVV4082 on KIV9. In conclusion, the generation of monoclonal antibody LPA-KIV9 may be a useful reagent in basic research studies and in the clinical application of Lp(a) measurements.




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Novel contact sites between lipid droplets, early endosomes, and the endoplasmic reticulum [Images in Lipid Research]




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High resolution structure of human apolipoprotein (a) kringle IV type 2: beyond the lysine binding site [Research Articles]

Lipoprotein (a) [Lp(a)] is characterized by an LDL-like composition in terms of lipids and apoB100, and by one copy of a unique glycoprotein, apo(a). The apo(a) structure is mainly based on the repetition of tandem kringle domains with high homology to plasminogen kringles 4 and 5. Among them, kringle IV type 2 (KIV-2) is present in a highly variable number of genetically encoded repeats, whose length is inversely related to Lp(a) plasma concentration and cardiovascular risk. Despite it being the major component of apo(a), the actual function of KIV-2 is still unclear. Here, we describe the first high-resolution crystallographic structure of this domain. It shows a general fold very similar to other KIV domains with high and intermediate affinity for the lysine analog, -aminocaproic acid. Interestingly, KIV-2 presents a lysine binding site (LBS) with a unique shape and charge distribution. KIV-2 affinity for predicted small molecule binders was found to be negligible in surface plasmon resonance experiments; and with the LBS being nonfunctional, we propose to rename it "pseudo-LBS". Further investigation of the protein by computational small-molecule docking allowed us to identify a possible heparin-binding site away from the LBS, which was confirmed by specific reverse charge mutations abolishing heparin binding. This study opens new possibilities to define the pathogenesis of Lp(a)-related diseases and to facilitate the design of specific therapeutic drugs.




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Cutting out the fat: Site-specific deacylation of an ion channel [Membrane Biology]

S-Acylation, a reversible post-translational lipid modification of proteins, controls the properties and function of various proteins, including ion channels. Large conductance Ca2+-activated potassium (BK) channels are S-acylated at two sites that impart distinct functional effects. Whereas the enzymes that attach lipid groups are known, the enzymes mediating lipid removal (i.e. deacylation) are largely unknown. Here, McClafferty et al. identify two enzymes, ABHD17a and ABHD17c, that excise BK channel lipid groups with remarkable precision. These findings lend insights into mechanisms that orchestrate the (de)acylation that fine-tunes ion channel function in physiology and disease.




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Site-specific deacylation by ABHD17a controls BK channel splice variant activity [Signal Transduction]

S-Acylation, the reversible post-translational lipid modification of proteins, is an important mechanism to control the properties and function of ion channels and other polytopic transmembrane proteins. However, although increasing evidence reveals the role of diverse acyl protein transferases (zDHHC) in controlling ion channel S-acylation, the acyl protein thioesterases that control ion channel deacylation are very poorly defined. Here we show that ABHD17a (α/β-hydrolase domain-containing protein 17a) deacylates the stress-regulated exon domain of large conductance voltage- and calcium-activated potassium (BK) channels inhibiting channel activity independently of effects on channel surface expression. Importantly, ABHD17a deacylates BK channels in a site-specific manner because it has no effect on the S-acylated S0–S1 domain conserved in all BK channels that controls membrane trafficking and is deacylated by the acyl protein thioesterase Lypla1. Thus, distinct S-acylated domains in the same polytopic transmembrane protein can be regulated by different acyl protein thioesterases revealing mechanisms for generating both specificity and diversity for these important enzymes to control the properties and functions of ion channels.




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Measuring Site-specific Glycosylation Similarity between Influenza a Virus Variants with Statistical Certainty [Research]

Influenza A virus (IAV) mutates rapidly, resulting in antigenic drift and poor year-to-year vaccine effectiveness. One challenge in designing effective vaccines is that genetic mutations frequently cause amino acid variations in IAV envelope protein hemagglutinin (HA) that create new N-glycosylation sequons; resulting N-glycans cause antigenic shielding, allowing viral escape from adaptive immune responses. Vaccine candidate strain selection currently involves correlating antigenicity with HA protein sequence among circulating strains, but quantitative comparison of site-specific glycosylation information may likely improve the ability to design vaccines with broader effectiveness against evolving strains. However, there is poor understanding of the influence of glycosylation on immunodominance, antigenicity, and immunogenicity of HA, and there are no well-tested methods for comparing glycosylation similarity among virus samples. Here, we present a method for statistically rigorous quantification of similarity between two related virus strains that considers the presence and abundance of glycopeptide glycoforms. We demonstrate the strength of our approach by determining that there was a quantifiable difference in glycosylation at the protein level between WT IAV HA from A/Switzerland/9715293/2013 (SWZ13) and a mutant strain of SWZ13, even though no N-glycosylation sequons were changed. We determined site-specifically that WT and mutant HA have varying similarity at the glycosylation sites of the head domain, reflecting competing pressures to evade host immune response while retaining viral fitness. To our knowledge, our results are the first to quantify changes in glycosylation state that occur in related proteins of considerable glycan heterogeneity. Our results provide a method for understanding how changes in glycosylation state are correlated with variations in protein sequence, which is necessary for improving IAV vaccine strain selection. Understanding glycosylation will be especially important as we find new expression vectors for vaccine production, as glycosylation state depends greatly on the host species.




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Depolarization-dependent Induction of Site-specific Changes in Sialylation on N-linked Glycoproteins in Rat Nerve Terminals [Research]

Synaptic transmission leading to release of neurotransmitters in the nervous system is a fast and highly dynamic process. Previously, protein interaction and phosphorylation have been thought to be the main regulators of synaptic transmission. Here we show that sialylation of N-linked glycosylation is a novel potential modulator of neurotransmitter release mechanisms by investigating depolarization-dependent changes of formerly sialylated N-linked glycopeptides. We suggest that negatively charged sialic acids can be modulated, similarly to phosphorylation, by the action of sialyltransferases and sialidases thereby changing local structure and function of membrane glycoproteins. We characterized site-specific alteration in sialylation on N-linked glycoproteins in isolated rat nerve terminals after brief depolarization using quantitative sialiomics. We identified 1965 formerly sialylated N-linked glycosites in synaptic proteins and found that the abundances of 430 glycosites changed after 5 s depolarization. We observed changes on essential synaptic proteins such as synaptic vesicle proteins, ion channels and transporters, neurotransmitter receptors and cell adhesion molecules. This study is to our knowledge the first to describe ultra-fast site-specific modulation of the sialiome after brief stimulation of a biological system.




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Meta-heterogeneity: evaluating and describing the diversity in glycosylation between sites on the same glycoprotein [Review]

Mass spectrometry-based glycoproteomics has gone through some incredible developments over the last few years. Technological advances in glycopeptide enrichment, fragmentation methods, and data analysis workflows have enabled the transition of glycoproteomics from a niche application, mainly focused on the characterization of isolated glycoproteins, to a mature technology capable of profiling thousands of intact glycopeptides at once. In addition to numerous biological discoveries catalyzed by the technology, we are also observing an increase in studies focusing on global protein glycosylation and the relationship between multiple glycosylation sites on the same protein. It has become apparent that just describing protein glycosylation in terms of micro- and macro-heterogeneity, respectively the variation and occupancy of glycans at a given site, is not sufficient to describe the observed interactions between sites. In this perspective we propose a new term, meta-heterogeneity, to describe a higher level of glycan regulation: the variation in glycosylation across multiple sites of a given protein. We provide literature examples of extensive meta-heterogeneity on relevant proteins such as antibodies, erythropoietin, myeloperoxidase and a number of serum and plasma proteins. Furthermore, we postulate on the possible biological reasons and causes behind the intriguing meta-heterogeneity observed in glycoproteins.




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Methods for Enrichment and Assignment of N-Acetylglucosamine Modification Sites [Review]

O-GlcNAcylation, the addition of a single N-acetylglucosamine residue to serine and threonine residues of cytoplasmic, nuclear, or mitochondrial proteins, is a widespread regulatory post-translational modification. It is involved in response to nutritional status and stress and its dysregulation is associated with diseases ranging from Alzheimer’s to diabetes.  While the modification was first detected over thirty-five years ago, research into the function of O-GlcNAcylation has accelerated dramatically in the last ten years due to the development of new enrichment and mass spectrometry techniques that facilitate its analysis.  This article summarizes methods for O-GlcNAc enrichment, key mass spectrometry instrumentation advancements, particularly those that allow modification site localization, and software tools that allow analysis of data from O-GlcNAc modified peptides.




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Site-specific N-glycosylation Characterization of Recombinant SARS-CoV-2 Spike Proteins [Research]

The glycoprotein spike (S) on the surface of SARS-CoV-2 is a determinant for viral invasion and host immune response. Herein, we characterized the site-specific N-glycosylation of S protein at the level of intact glycopeptides. All 22 potential N-glycosites were identified in the S-protein protomer and were found to be preserved among the 753 SARS-CoV-2 genome sequences. The glycosites exhibited glycoform heterogeneity as expected for a human cell-expressed protein subunit. We identified masses that correspond to 157 N-glycans, primarily of the complex type. In contrast, the insect cell-expressed S protein contained 38 N-glycans, completely of the high-mannose type. Our results revealed that the glycan types were highly determined by the differential processing of N-glycans among human and insect cells, regardless of the glycosites’ location. Moreover, the N-glycan compositions were conserved among different sizes of subunits. Our study indicate that the S protein N-glycosylation occurs regularly at each site, albeit the occupied N-glycans were diverse and heterogenous. This N-glycosylation landscape and the differential N-glycan patterns among distinct host cells are expected to shed light on the infection mechanism and present a positive view for the development of vaccines and targeted drugs.




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Protein modification characteristics of the malaria parasite Plasmodium falciparum and the infected erythrocytes [Research]

Malaria elimination is still pending on the development of novel tools that rely on a deep understanding of parasite biology. Proteins of all living cells undergo a myriad number of posttranslational modifications (PTMs) that are critical to multifarious life processes. An extensive proteome-wide dissection revealed a fine PTM map of most proteins in both Plasmodium falciparum, the causative agent of severe malaria, and the infected red blood cells. More than two-thirds of proteins of the parasite and its host cell underwent extensive and dynamic modification throughout the erythrocytic developmental stage. PTMs critically modulate the virulence factors involved in the host-parasite interaction and pathogenesis. Furthermore, P. falciparum stabilized the supporting proteins of erythrocyte origin by selective de-modification. Collectively, our multiple omic analyses, apart from having furthered a deep understanding of the systems biology of P. falciparum and malaria pathogenesis, provide a valuable resource for mining new antimalarial targets.




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High-throughput and site-specific N-glycosylation analysis of human alpha-1-acid glycoprotein offers a great potential for new biomarker discovery [Research]

Alpha-1-acid glycoprotein (AGP) is an acute phase glycoprotein in blood, which is primarily synthetized in the liver and whose biological role is not completely understood. It consists of 45% carbohydrates that are present in the form of five N-linked complex glycans. AGP N-glycosylation was shown to be changed in many different diseases and some changes appear to be disease-specific, thus it has a great diagnostic and prognostic potential. However, AGP glycosylation was mainly analyzed in small cohorts and without detailed site-specific glycan information. Here, we developed a cost-effective method for a high-throughput and site-specific N-glycosylation LC-MS analysis of AGP which can be applied on large cohorts, aid in search for novel disease biomarkers and enable better understanding of AGP’s role and function in health and disease. The method does not require isolation of AGP with antibodies and affinity chromatography, but AGP is enriched by acid precipitation from 5 μl of bloodplasma in a 96 well format. After trypsinization, AGP glycopeptides are purified using a hydrophilic interaction chromatography based solid-phase extraction and analyzed by RP-LC-ESI-MS. We used our method to show for the first time that AGP N-glycan profile is stable in healthy individuals (14 individuals in 3 time points), which is a requirement for evaluation of its diagnostic potential. Furthermore, we tested our method on a population including individuals with registered hyperglycemia in critical illness (59 cases and 49 controls), which represents a significantly increased risk of developing type 2 diabetes. Individuals at higher risk of diabetes presented increased N-glycan branching on AGP’s second glycosylation site and lower sialylation of N-glycans on AGP’s third and AGP1’s fourth glycosylation site. Although this should be confirmed on a larger prospective cohort, it indicates that site-specific AGP N-glycan profile could help distinguish individuals who are at risk of type 2 diabetes.




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Composite Prediction Score to Interpret Bone Focal Uptake in Hormone-Sensitive Prostate Cancer Patients Imaged with [18F]PSMA-1007 PET/CT

Unspecific bone uptake (UBU) related to [18F]PSMA-1007 PET/CT imaging represents a clinical challenge. We aimed to assess whether a combination of clinical, biochemical, and imaging parameters could predict skeletal metastases in patients with [18F]PSMA-1007 bone focal uptake, aiding in result interpretation. Methods: We retrospectively analyzed [18F]PSMA-1007 PET/CT performed in hormone-sensitive prostate cancer (PCa) patients at 3 tertiary-level cancer centers. A fourth center was involved in performing an external validation. For each, a volume of interest was drawn using a threshold method to extract SUVmax, SUVmean, PSMA tumor volume, and total lesion PSMA. The same volume of interest was applied to CT images to calculate the mean Hounsfield units (HUmean) and maximum Hounsfield units. Clinical and laboratory data were collected from electronic medical records. A composite reference standard, including follow-up histopathology, biochemistry, and imaging data, was used to distinguish between PCa bone metastases and UBU. PET readers with less (n = 2) or more (n = 2) experience, masked to the reference standard, were asked to visually rate a subset of focal bone uptake (n = 178) as PCa metastases or not. Results: In total, 448 bone [18F]PSMA-1007 focal uptake specimens were identified in 267 PCa patients. Of the 448 uptake samples, 188 (41.9%) corresponded to PCa metastases. Ongoing androgen deprivation therapy at PET/CT (P < 0.001) with determination of SUVmax (P < 0.001) and HUmean (P < 0.001) independently predicted bone metastases. A composite prediction score, the bone uptake metastatic probability (BUMP) score, achieving an area under the receiver-operating-characteristic curve (AUC) of 0.87, was validated through a 10-fold internal and external validation (n = 89 bone uptake, 51% metastatic; AUC, 0.92). The BUMP score’s AUC was significantly higher than that of HUmean (AUC, 0.62) and remained high among lesions with HUmean in the first tertile (AUC, 0.80). A decision-curve analysis showed a higher net benefit with the score. Compared with the visual assessment, the BUMP score provided added value in terms of specificity in less-experienced PET readers (88% vs. 54%, P < 0.001). Conclusion: The BUMP score accurately distinguished UBU from bone metastases in PCa patients with [18F]PSMA-1007 focal bone uptake at PET imaging, offering additional value compared with the simple assessment of the osteoblastic CT correlate. Its use could help clinicians interpret imaging results, particularly those with less experience, potentially reducing the risk of patient overstaging.




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Mattel apologizes for misprint on 'Wicked' doll packaging that links to porn website

Mattel has apologized after inadvertently directing customers of its new line of Wicked dolls to a pornographic website, stating it is taking action to remove the misprinted toys' packaging.




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SDSC Leads Expansion of Open Storage Network to More Campus Computing Sites

Oct. 24, 2024 — The San Diego Supercomputer Center (SDSC), part of the School of Computing, Information and Data Sciences at UC San Diego, has been leading the Open Storage Network (OSN) program for years, and along […]

The post SDSC Leads Expansion of Open Storage Network to More Campus Computing Sites appeared first on HPCwire.




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Mattel apologizes for misprint on 'Wicked' doll packaging that links to porngraphic website

Mattel has apologized after inadvertently directing customers of its new line of Wicked dolls to a pornographic website, stating it is taking action to remove the misprinted toys' packaging.




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Hacked websites, hate speech hit suburban Chicago schools




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Electrocortical Responses in Anticipation of Avoidable and Inevitable Threats: A Multisite Study

When faced with danger, human beings respond with a repertoire of defensive behaviors, including freezing and active avoidance. Previous research has revealed a pattern of physiological responses, characterized by heart rate bradycardia, reduced visual exploration, and heightened sympathetic arousal in reaction to avoidable threats, suggesting a state of attentive immobility in humans. However, the electrocortical underpinnings of these behaviors remain largely unexplored. To investigate the visuocortical components of attentive immobility, we recorded parieto-occipital alpha activity, along with eye movements and autonomic responses, while participants awaited either an avoidable, inevitable, or no threat. To test the robustness and generalizability of our findings, we collected data from a total of 101 participants (76 females, 25 males) at two laboratories. Across sites, we observed an enhanced suppression of parieto-occipital alpha activity during avoidable threats, in contrast to inevitable or no threat trials, particularly toward the end of the trial that prompted avoidance responses. This response pattern coincided with heart rate bradycardia, centralization of gaze, and increased sympathetic arousal. Furthermore, our findings expand on previous research by revealing that the amount of alpha suppression, along with centralization of gaze, and heart rate changes predict the speed of motor responses. Collectively, these findings indicate that when individuals encounter avoidable threats, they enter a state of attentive immobility, which enhances perceptual processing and facilitates action preparation. This state appears to reflect freezing-like behavior in humans.




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See a Film That Reimagines History on the Malaysian Island That Served as a Refugee Site After the Vietnam War

The work, now on view at the Smithsonian American Art Museum, tells the story of two characters on the island—the last people alive in the world




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The new FAO corporate web site

On 16 November, an upgraded, fully mobile-responsive corporate [...]




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Three sites in China designated FAO Globally Important Agricultural Heritage Systems

Three sites in China - an ancient tea-producing area, a nomadic livestock-rearing region and a rain-fed stone terrace farming system - were formally recognised  as Globally Important Agricultural Heritage [...]




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Two new sites in Japan designated FAO Globally Important Agricultural Heritage Systems

Rome - Two new sites in Japan - an inland fisheries and associated paddy farming system centred on the country’s largest lake and a traditional fruit-growing area  believed to have been the [...]




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The Food and Agriculture Organization of the United Nations (FAO) launches its new Annual and Monthly Funding Overview websites

Rome – The newly released Annual Report for 2020, 2021 and 2022 raises the visibility of the Organization's Resource Partners, including FAO Members, international financial institutions (IFIs), United Nations entities, [...]




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New Technical Cooperation Programme Website

The PSS Technical Cooperation Programme (TCP) team is excited to announce the launch of its newly designed webpages. The webpage has a fresh look [...]




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Three new sites recognized as Globally Important Agricultural Heritage Systems (GIAHS)

Indonesia and Sao Tome and Principe receive their first designations from FAO along with Austria’s second system




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How We See Oppenheimer. Plus: Smithsonian’s Inside Look at the Top-Secret Los Alamos Site

Christopher Nolan's epic new film "Oppenheimer" is no mere biopic… nor is it the first attempt to capture the father of the atomic bomb in fiction. We look at prior dramatizations of this very complicated man—including one wherein J. Robert Oppenheimer played himself!—and examine why they worked or didn't. In the episode: Physicist-turned-photographer Minesh Bacrania shares his experience photographing inside the top-secret labs at Los Alamos National Laboratory, where J. Robert Oppenheimer and other scientists created the first nuclear weapon. Next, with Christopher Nolan’s film Oppenheimer exceeding commercial expectations, Smithsonian magazine writer Andy Kifer discusses the complexities of Oppenheimer's genius and how prior attempts to depict him in film and television and on stage have fared. Read Andy Kifer’s “The Real Story Behind Christopher Nolan’s Oppenheimer” here (https://www.smithsonianmag.com/history/the-real-history-behind-christopher-nolans-oppenheimer-180982529/) . See Minesh Bacrania’s photographs of Los Alamos and read Smithsonian senior editor Jennie Rothenberg Gritz’s text here (https://www.smithsonianmag.com/history/exclusive-behind-scenes-look-los-alamos-lab-where-robert-oppenheimer-created-atomic-bomb-180982336/) or in the July/August 2023 issue of Smithsonian. There’s More to That is a production of Smithsonian magazine and PRX Productions. From the magazine, our team is Chris Klimek, Debra Rosenberg and Brian Wolly. From PRX, our team is Jessica Miller, Genevieve Sponsler, Adriana Rozas Rivera, Terence Bernardo, and Edwin Ochoa. The Executive Producer of PRX Productions is Jocelyn Gonzales. Episode artwork by Emily Lankiewicz. Music by APM Music.




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Polar Bears Are Exposed to More Parasites, Viruses and Bacteria as the Arctic Heats Up

Pathogens are more common in polar bears living in the Chukchi Sea now than they were three decades ago, a new study suggests—but it's not yet clear what that means for the mammals' health




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Bosch Rexroth gives global sales, Web site traffic a lift with 3D PartStream.NET-powered interactive catalog

Company's Linear Motion and Assembly Technologies Group increases sales by 40 percent, leads by 25 percent, with redesigned Web site featuring downloadable 3D models




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Fabco-Air boosts sales, Web site traffic with interactive online storefront powered by 3D PartStream.NET

Pneumatic product manufacturer sees more than 80 percent increase in 3D model downloads in first two months




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Mead boosts Web site traffic, helps customers streamline product development with 3D PartStream.NET-powered interactive 3D catalog

Customized valve and cylinder maker sees 420 percent increase in online transactions in the first three months




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SolidWorks tops industry for promoting education and producing best Web site, according to Design News readers

Strong education programs, key sponsorships, and intuitive software put company on top




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Education Week American Education News Site of Record - News

News.




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Office of Digital Learning creates platform to simplify website content creation

Developed by a team in the College of Arts and Architecture's Office of Digital Learning, HAX, or Headless Authoring eXperience, is a content management system that structures content in a ubiquitous format for simple web publishing.




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Delaware State Housing Authority Announces The Launch Of Its New And Improved Website

The Delaware State Housing Authority (DSHA) announced today the launch of its new and improved user-friendly website: https://www.destatehousing.com/. The new website was designed with the public and partners in mind, providing them easy access to services, resources, and information. The new website offers a fresh look and enhanced features like site translation services, improved search […]



  • Delaware State Housing Authority

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DSCYF Shares Redesigned Website

WILMINGTON – The Delaware Department of Services for Children, Youth and Their Families is sharing the agency’s newly redesigned website. Launched Thursday, July 29, the website redesign of kids.delaware.gov was in coordination with the Department’s rebranding over the last year, which has included a new, updated logo. Throughout this process, DSCYF worked with the Department […]



  • Department of Services for Children
  • Youth and their Families

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Jio Star Website Goes Live Ahead of Anticipated Merger of Reliance Jio and Disney+ Hotstar

The merger between Reliance Jio’s Viacom18 and Star India Private Limited is expected to reach its conclusion this week. Ahead of the anticipated completion, a new website has surfaced which could allegedly be the home of the new OTT service formed courtesy of the amalgamation of JioCinema and Disney+ Hotstar — two popular streaming services in India.




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Anushka Sharma And Virat Kohli Visited Benne Dosa In Mumbai But An Employee Stole The Spotlight

Anushka Sharma and Virat Kohli seemed to have a good South Indian meal at the restaurant. Anushka also reposted the restaurants post ionher Instagram Stories




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Division of Small Business Now Accepting Applications for Site Readiness Fund

The Delaware Division of Small Business is now accepting applications for the Site Readiness Fund from qualified businesses or local governments. Established through Senate Bill 127, the fund promotes economic growth and stability by investing in the development or improvement of commercial and industrial sites to attract job-creating businesses. The Site Readiness Fund provides grants, […]




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Council on Development Finance Approves Eight Site Readiness Fund Projects Totaling $6.2 million

NEW CASTLE, DE (March 28, 2022) – The Council on Development Finance (CDF) on Monday approved eight Site Readiness Fund project applications totaling $6.2 million. The projects are located throughout the state with three each in New Castle County and Kent County and two in Sussex County. Established through Senate Bill 127, the Site Readiness […]




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Division of Small Business Launches Innovative New Website Service Designed to Support Delaware’s Small Businesses

DOVER, Del. – The Delaware Division of Small Business launched SizeUpDelaware this week, making powerful market research and business intelligence available to small businesses to help them succeed. Small business owners in Delaware can now access industry-specific and hyperlocal information to help them grow and make smarter decisions using Big Data analysis. The research is individually […]




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Division of Small Business Accepting Applications for Site Readiness Fund

DOVER, Del. (August 1, 2022) – The Delaware Division of Small Business announced today that it is now accepting applications for the Site Readiness Fund from qualified businesses or local governments. Established through Senate Bill 127, the fund promotes economic growth and stability by investing in the development or improvement of commercial and industrial sites […]





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DDOL Responds to Jobseeker Site Breach

Updated, March 23, 2017 – A list of Frequently Asked Questions is being maintained on the DDOL website. Wilmington – March 22, 2017 America’s JobLink (AJL) web-based system that links job seekers with employers in Delaware and nine other states was hacked by a malicious third party last week. Approximately 253,420 Delaware JobLink users dating […]



  • Department of Labor
  • News

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Delaware Department of Labor Announces New Features and Updates to the Delaware JobLink Website

Wilmington, Delaware February 22, 2021 Delaware Department of Labor FOR IMMEDIATE RELEASE   WILMINGTON, DE – Delaware Department of Labor has added new functionality to the Delaware JobLink (joblink.delaware.gov), a website created to support employers looking for qualified candidates, and individuals seeking employment.   The current website offers individuals the ability to search for jobs, […]




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FRAUD ALERT: The U.S. Justice Department Warns About Fake Unemployment Benefit Websites

The U.S. Department of Justice has received reports that fraudsters are creating websites mimicking unemployment benefit websites, including state workforce agency (SWA) websites, and Facebook pages to unlawfully capture consumers’ personal information.   To lure consumers to these fake websites, fraudsters send spam text messages and emails purporting to be from an SWA and containing […]



  • Department of Labor
  • Division of Unemployment
  • Unemployment
  • unemployment insurance benefits