Perlecan is a critical proteoglycan found in the extracellular matrix (ECM) of cartilage. In healthy cartilage, perlecan regulates cartilage biomechanics and we previously demonstrated perlecan deficiency leads to reduced cellular and ECM stiffness in vivo. This change in mechanics may lead to the early onset osteoarthritis seen in disorders resulting from perlecan knockdown such as Schwartz-Jampel syndrome (SJS). To identify how perlecan knockdown affects the material properties of developing cartilage, we used imaging and liquid chromatography–tandem mass spectrometry (LC-MS/MS) to study the ECM in a murine model of SJS, Hspg2C1532Y-Neo. Perlecan knockdown led to defective pericellular matrix formation, whereas the abundance of bulk ECM proteins, including many collagens, increased. Post-translational modifications and ultrastructure of collagens were not significantly different; however, LC-MS/MS analysis showed more protein was secreted by Hspg2C1532Y-Neo cartilage in vitro, suggesting that the incorporation of newly synthesized ECM was impaired. In addition, glycosaminoglycan deposition was atypical, which may explain the previously observed decrease in mechanics. Overall, these findings provide insight into the influence of perlecan on functional cartilage assembly and the progression of osteoarthritis in SJS.

A fundamental feature of the eukaryotic cell membrane is the asymmetric arrangement of lipids in its two leaflets. A cell invests significant energy to maintain this asymmetry and uses it to regulate important biological processes, such as apoptosis and vesiculation. The dynamic coupling of the inner or cytoplasmic and outer or exofacial leaflets is a challenging open question in membrane biology. Here, we combined fluorescence lifetime imaging microscopy (FLIM) with imaging total internal reflection fluorescence correlation spectroscopy (ITIR-FCS) to differentiate the dynamics and organization of the two leaflets of live mammalian cells. We characterized the biophysical properties of fluorescent analogs of phosphatidylcholine, sphingomyelin, and phosphatidylserine in the plasma membrane of two mammalian cell lines (CHO-K1 and RBL-2H3). Because of their specific transverse membrane distribution, these probes allowed leaflet-specific investigation of the plasma membrane. We compared the results of the two methods having different temporal and spatial resolution. Fluorescence lifetimes of fluorescent lipid analogs were in ranges characteristic for the liquid ordered phase in the outer leaflet and for the liquid disordered phase in the inner leaflet. The observation of a more fluid inner leaflet was supported by free diffusion in the inner leaflet, with high average diffusion coefficients. The liquid ordered phase in the outer leaflet was accompanied by slower diffusion and diffusion with intermittent transient trapping. Our results show that the combination of FLIM and ITIR-FCS with specific fluorescent lipid analogs is a powerful tool for investigating lateral and transbilayer characteristics of plasma membrane in live cell lines.

In his first public address on his inaugural official visit to Washington, DC, IOM Director General António Vitorino discusses his vision for IOM; reforms in the UN system; coordination with other organizations in addressing humanitarian protection; and the operational steps IOM is taking to respond to forced migration and displacement.

In his first public address during his inaugural formal visit to Washington, DC. International Organization for Migration (IOM) Director General António Vitorino discussed his vision for the agency; reforms in the UN system designed to address migration matters better; the coordination of efforts between IOM, the UN High Commissioner for Refugees, and other international partners in addressing humanitarian protection; and the operational steps IOM is taking to respond to forced migration and displacement in hotspots around the world, including Venezuela, Bangladesh, and Libya.

Francesco Rubino
Jun 1, 2016; 39:861-877
Metabolic Surgery and the Changing Landscape for Diabetes Care

Francesco Rubino
Jun 1, 2016; 39:861-877
Metabolic Surgery and the Changing Landscape for Diabetes Care

The ADA, along with a large group of other dental organizations, told the U.S. Department of Labor that they are concerned about provisions in HR 6201, the Families First Coronavirus Response Act as related to family and medical leave and paid sick leave.

The ADA and nearly 100 other organizations are asking Congress and the White House to help businesses survive the coronavirus crisis by reducing their costs and increasing their cash flow as much as possible in the coming weeks.

The ADA and other health care organizations signed a public statement March 27 saying they “strongly” support emergency efforts at the federal level to dramatically increase the production and distribution of personal protective equipment (PPE) and other necessary medical equipment and supplies during the COVID-19 pandemic.

The ADA, Organized Dentistry Coalition, and many state dental associations are asking the U.S. Department of Health and Human Services and Centers for Medicare & Medicaid Services to release funding from the Coronavirus Aid, Relief and Economic Security Act Provider Relief Fund to assist dental Medicaid providers.

Days before the Sept. 11, 2001, attacks, Osama bin Laden left his compound in Kandahar in Afghanistan and headed into the mountains. His driver, Salim Ahmed Hamdan, traveled with him. As U.S. and Northern Alliance forces stood poised to capture Kandahar a few months later, bin Laden told Hamdan t...

Geneva, Switzerland : World Health Organization, 1988.

Catherine Mankiw
May 24, 2017; 37:5221-5231
Development Plasticity Repair

Fiona Doetsch
Jul 1, 1997; 17:5046-5061
Articles

FAO email newsletters have sparked great interest across the Organization in the last few years, with over 2 million emails sent out in 2018 and over 3 million last year.

Corporate newsletters cover approximately 100 [...]

Tourism Cavendish Beach says it is hopeful the Confederation Bridge and province will reopen to certain visitors as soon as it is safe to do so.

For the first time, the World Health Organization has officially designated "gaming disorder" among its list of mental-health addictive behaviors.

Accountable care organizations are expanding. In pediatrics, however, there is no information on cost savings or quality generated by such organizations.

Partners for Kids is a pediatric accountable care organization that increased value for Medicaid children in 34 Ohio counties, primarily through cost savings. This slowing in cost growth was achieved without diminishing the overall quality or outcomes of care. (Read the full article)

Bridget O’Donnell, assistant director of student engagement at Penn State Brandywine, has been recognized as Advisor of the Year by the Association for the Promotion of Campus Activities.

Rebecca Mattson, head of faculty and research services for the H. Laddie Montague Jr. Law Library, Penn State University Libraries, and professor of legal research at Penn State Law at University Park, has been elected vice chair/chair elect of the Research Instruction and Patron Services Special Interest Section of the American Association of Law Libraries.

The Rural School and Community Trust and the AASA, the School Superintendents Association, say the partnership will allow the two groups to expand their reach and play off each other's strengths.

FISCAL YEAR 2019 GRANT APPLICATIONS FOR DELAWARE ARTS & COMMUNITY-BASED ORGANIZATIONS AND SCHOOLS NOW OPEN Wilmington, Del. (December 12, 2017) – The Delaware Division of the Arts has opened its annual online grant application process for grants for arts programming and projects taking place during fiscal year 2019 (September 2018 – August 2019). Applications are due […]

For arts programming and projects taking place during fiscal year 2020 (September 2019 – August 2020) Wilmington, Del. (December 13, 2018) – The Delaware Division of the Arts has opened its annual online application process for grants for arts programming and projects taking place during fiscal year 2020 (September 2019 – August 2020). Applications will be […]

For arts programming and projects taking place during fiscal year 2020 (September 2019 – August 2020) Wilmington, Del. (December 5, 2019) – The Delaware Division of the Arts has opened its annual online application process for grants for arts programming and projects taking place during fiscal year 2021 (September 2020 – August 2021). Applications will […]

Two Delaware racing officials have been named chairman and secretary of the Organization of Racing Investigators, which represents racetracks, regulatory agencies and law enforcement involved in upholding the integrity of horse racing.

To reduce disparate birth outcomes and save the lives of both infants and their mothers, the Division of Public Health (DPH) and the Delaware Healthy Mother and Infant Consortium (DHMIC) awarded mini-grants to six community organizations. The local grant recipients were announced Dec. 10, during the DHMIC’s quarterly meeting in Dover.

Eligible applicants include those that received General Operating Support from FY 18/19/20 or Project Support from FY20 Wilmington, DE (April 30, 2020) – The Delaware Division of the Arts, with support from the National Endowment for the Arts through the Coronavirus Aid, Relief, and Economic Security (CARES) Act, has developed a program to help secure […]

Renewable energy, particularly solar, is poised for significant growth in the southeastern United States. The Southeast has also mostly retained a vertically integrated utility model, and most utilities in the region have not joined a Regional Transmission Organization or Independent System Operator (collectively known as, RTO). Recent developments have led stakeholders and policymakers in the Southeast to rethink whether it is beneficial for some utilities to join RTOs – something that is generally seen as a positive development for renewable energy.

Temporary protection against creditors In these uncertain times, companies are confronted with a severe decline in their turnover, often resulting in cash-flow problems. Through the judicial reorganization procedure, these companies can apply for te...

In these uncertain times, there is a good chance that your company will be confronted with a contracting party that is in the process of judicial reorganization, or that you have initiated this procedure yourself. What are the consequences of this p...

International aid workers are having a tremendously difficult time doing their jobs due to all the travel bans around the world and other quarantine measures. In the face of the coronavirus, however, they are needed more than ever before.

The World Health Organization is the most important authority in the global battle against the coronavirus. But doubts about the WHO’s leadership are growing, and not just in Washington. Is Director General Tedros up to the task?

One of the major challenges posed by the rapid growth in the use of AI is whether or not existing IP systems are adequate to deal with the ownership and exploitation of AI-assisted and AI-generated products, processes, works and designs, which is so...

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Key Points

Viruses and mobile genetic elements are molecular parasites or symbionts that coevolve with nearly all forms of cellular life. The route of virus replication and protein expression is determined by the viral genome type. Comparison of these routes led to the classification of viruses into seven "Baltimore classes" (BCs) that define the major features of virus reproduction. However, recent phylogenomic studies identified multiple evolutionary connections among viruses within each of the BCs as well as between different classes. Due to the modular organization of virus genomes, these relationships defy simple representation as lines of descent but rather form complex networks. Phylogenetic analyses of virus hallmark genes combined with analyses of gene-sharing networks show that replication modules of five BCs (three classes of RNA viruses and two classes of reverse-transcribing viruses) evolved from a common ancestor that encoded an RNA-directed RNA polymerase or a reverse transcriptase. Bona fide viruses evolved from this ancestor on multiple, independent occasions via the recruitment of distinct cellular proteins as capsid subunits and other structural components of virions. The single-stranded DNA (ssDNA) viruses are a polyphyletic class, with different groups evolving by recombination between rolling-circle-replicating plasmids, which contributed the replication protein, and positive-sense RNA viruses, which contributed the capsid protein. The double-stranded DNA (dsDNA) viruses are distributed among several large monophyletic groups and arose via the combination of distinct structural modules with equally diverse replication modules. Phylogenomic analyses reveal the finer structure of evolutionary connections among RNA viruses and reverse-transcribing viruses, ssDNA viruses, and large subsets of dsDNA viruses. Taken together, these analyses allow us to outline the global organization of the virus world. Here, we describe the key aspects of this organization and propose a comprehensive hierarchical taxonomy of viruses.

The Stenotrophomonas maltophilia complex (Smc) comprises opportunistic environmental Gram-negative bacilli responsible for a variety of infections in both humans and animals. Beyond its large genetic diversity, its genetic organization in genogroups was recently confirmed through the whole-genome sequencing of human and environmental strains. As they are poorly represented in these analyses, we sequenced the whole genomes of 93 animal strains to determine their genetic background and characteristics. Combining these data with 81 newly sequenced human strains and the genomes available from RefSeq, we performed a genomic analysis that included 375 nonduplicated genomes with various origins (animal, 104; human, 226; environment, 30; unknown, 15). Phylogenetic analysis and clustering based on genome-wide average nucleotide identity confirmed and specified the genetic organization of Smc in at least 20 genogroups. Two new genogroups were identified, and two previously described groups were further divided into two subgroups each. Comparing the strains isolated from different host types and their genogroup affiliation, we observed a clear disequilibrium in certain groups. Surprisingly, some antimicrobial resistance genes, integrons, and/or clusters of attC sites lacking integron-integrase (CALIN) sequences targeting antimicrobial compounds extensively used in animals were mainly identified in animal strains. We also identified genes commonly found in animal strains coding for efflux systems. The result of a large whole-genome analysis performed by us supports the hypothesis of the putative contribution of animals as a reservoir of Stenotrophomonas maltophilia complex strains and/or resistance genes for strains in humans.

IMPORTANCE Given its naturally large antimicrobial resistance profile, the Stenotrophomonas maltophilia complex (Smc) is a set of emerging pathogens of immunosuppressed and cystic fibrosis patients. As it is group of environmental microorganisms, this adaptation to humans is an opportunity to understand the genetic and metabolic selective mechanisms involved in this process. The previously reported genomic organization was incomplete, as data from animal strains were underrepresented. We added the missing piece of the puzzle with whole-genome sequencing of 93 strains of animal origin. Beyond describing the phylogenetic organization, we confirmed the genetic diversity of the Smc, which could not be estimated through routine phenotype- or matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF)-based laboratory tests. Animals strains seem to play a key role in the diversity of Smc and could act as a reservoir for mobile resistance genes. Some genogroups seem to be associated with particular hosts; the genetic support of this association and the role of the determinants/corresponding genes need to be explored.

Canada has backed an American-led effort to allow Taiwan to be granted observer status at the World Health Organization because of its early success in containing COVID-19.

“My family and I have made the decision to return to Oregon,” the 36-year-old said in a video address posted Thursday on the Lions website.

A First Nations financial organization in the Atlantic region is voicing concern over the exclusion of band-owned, non-taxable businesses in federal financial relief programs during the COVID-19 pandemic.

Today the Departments of Justice, State and Treasury announced coordinated actions against the Gulf Cartel/Los Zetas drug trafficking organization, now known as the "Company," in the latest in a series of efforts by the U.S. government to neutralize and dismantle this violent cartel.

Consuelo Carreto Valencia, a member of the Carreto family sex trafficking ring that operated between Mexico and Queens, N.Y., was sentenced to 121 months in prison for benefitting financially from her participation in the organization, which transported young Mexican women to the United States and forced them into prostitution.

A federal grand jury in Trenton, N.J., has charged Vincent Johnson of Brick, N.J., with threatening employees of five civil rights organizations that work to improve opportunities for and challenge discrimination against Latinos in the United States.

"Let me be clear, we enhance public safety by incarcerating those who harm our neighbors and our communities. This is a fact. But in our work to protect the American people, incarceration cannot be our only law enforcement strategy," said Attorney General Holder.

The former acting executive director of U’una’i Legal Services Corporation pleaded guilty today to stealing $31,292 from the federally-funded organization in American Samoa.

The Attorney General’s annual victims’ service awards are presented as a prelude to the nation’s observance of National Crime Victims’ Rights Week, April 18-April 24, 2010.