The bone marrow niche is a complex and dynamic structure composed of a multitude of cell types which functionally create an interactive network facilitating hematopoietic stem cell development and maintenance. Its specific role in the pathogenesis, response to therapy, and transformation of myeloproliferative neoplasms has only recently been explored. Niche functionality is likely affected not only by the genomic background of the myeloproliferative neoplasm-associated mutated hematopoietic stem cells, but also by disease-associated ‘chronic inflammation’, and subsequent adaptive and innate immune responses. ‘Cross-talk’ between mutated hematopoietic stem cells and multiple niche components may contribute to propagating disease progression and mediating drug resistance. In this timely article, we will review current knowledge surrounding the deregulated bone marrow niche in myeloproliferative neoplasms and suggest how this may be targeted, either directly or indirectly, potentially influencing therapeutic choices both now and in the future.

Purpose:

KEYNOTE-158 (ClinicalTrials.gov identifier: NCT02628067) investigated the efficacy and safety of pembrolizumab across multiple cancers. We present results from patients with previously treated advanced well-differentiated neuroendocrine tumors (NET).

Chromosomal resistance islands containing the methicillin resistance gene mecD (McRI_mecD) have been reported in Macrococcus caseolyticus. Here, we identified novel macrolide resistance genes in Macrococcus canis on similar elements, called McRI_msr. These elements were also integrated into the 3' end of the 30S ribosomal protein S9 gene (rpsI), delimited by characteristic attachment (att) sites, and carried a related site-specific integrase gene (int) at the 5' end. They carried novel macrolide resistance genes belonging to the msr family of ABC subfamily F (ABC-F)-type ribosomal protection protein [msr(F) and msr(H)] and the macrolide efflux mef family [mef(D)]. Highly related mef(D)-msr(F) fragments were found on diverse McRI_msr elements in M. canis, M. caseolyticus, and Staphylococcus aureus. Another McRI_msr-like element identified in an M. canis strain lacked the classical att site at the 3' end and carried the msr(H) gene but no neighboring mef gene. The expression of the novel resistance genes in S. aureus resulted in a low-to-moderate increase in the MIC of erythromycin but not streptogramin B. In the mef(D)-msr(F) operon, the msr(F) gene was shown to be the crucial determinant for macrolide resistance. The detection of circular forms of McRI_msr and the mef(D)-msr(F) fragment suggested mobility of both the island and the resistance gene subunit. The discovery of McRI_msr in different Macrococcus species and S. aureus indicates that these islands have a potential for dissemination of antibiotic resistance within the Staphylococcaceae family.

After self-isolating for two weeks she plans to attend another rally

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Here's a look at the number of coronavirus cases in North Carolina and the latest news about the COVID-19 outbreak.

Here's a look at the number of coronavirus cases in South Carolina and the latest news about the COVID-19 outbreak.

The US District Court in Delaware issued a decision upholding the validity of patent claims from three…

Three air cargo carriers, LAN Cargo S.A. (LAN Cargo), Aerolinhas Brasileiras S.A. (ABSA), and EL AL Israel Airlines Ltd. (EL AL), have each agreed to plead guilty and pay criminal fines totaling $124.7 million for their roles in a conspiracy to fix prices in the air cargo industry.

Timothy Christenbury, of Charlotte, N.C., pleaded guilty today to possessing child pornography. Christenbury, 46, pleaded guilty before U.S. Magistrate Judge Carl Horn III to one count of possession of child pornography. He was indicted on those charges on Dec. 16, 2008. According to the indictment, Christenbury possessed computer files containing child pornography from on or about Sept. 2 to Sept. 4, 2007.

The Department announced today that it has reached a settlement that, if approved by the court, will resolve a lawsuit filed by the Department against the Administrative Office of the Courts of the State of North Carolina and the Honorable Jerry Braswell, Senior Resident Superior Court Judge for North Carolina Judicial District 8-B, in his official capacity.

The United States has sued tax return preparers in Placerville, Calif., and Columbia, S.C., seeking to bar them from preparing federal tax returns for others. According to the government complaints in the two cases, Teresa Marty of Pollock Pines, Calif., and Winston Able of Blythewood, S.C., prepare federal income tax returns for their customers that claim fraudulent tax refunds.

A federal court has permanently barred Raymond A. Renfrow of Elm City, N.C., from preparing federal income tax returns for others. The U.S. District Court for the Eastern District of North Carolina entered the civil injunction order, which also stops Renfrow from promoting a tax fraud scheme that used sham trusts to falsely deduct customers’ non-deductible personal expenses.

A federal grand jury in Florence, S.C., indicted three men from Marlboro County, S.C., on charges relating to their attack on an African-American man and two white men in December 2007.

The Department has filed suit against the town of Garner, N.C., and the town’s board of adjustment alleging that they violated the Fair Housing Act when they refused to allow up to eight men recovering from drug and alcohol addictions to live together as a reasonable accommodation for their disabilities.

Seven individuals have been charged with conspiring to provide material support to terrorists and conspiring to murder, kidnap, maim and injure persons abroad.

Rodney K. Justin, a medical doctor from Woodleaf, N.C., was convicted yesterday of obstructing the internal revenue laws and of failing to file tax returns for several years. After trial in Winston-Salem, N.C., a federal jury convicted Justin of four felony counts of corruptly obstructing the administration of the internal revenue laws by sending fake financial instruments called “Bills of Exchange” to the Secretary of the Treasury in Washington, D.C., in purported payment of over $350,000 in taxes.

The Justice Department today filed a lawsuit in federal court in Raleigh, N.C., against Franklin County, N.C., alleging that the county retaliated against a former employee in its Department of Public Utilities, in violation of Title VII of the Civil Rights Act of 1964, after the employee complained about sexual harassment by a co-worker.

The Department has reached a consent decree with Franklin County, N.C., that, if approved in federal court in Raleigh, N.C., will resolve the department’s allegation that the county retaliated against a former employee in its Department of Public Utilities, in violation of Title VII of the Civil Rights Act of 1964.

The agreement was reached under “Project Civic Access,” a Justice Department initiative to bring state and local governments into compliance with the Americans with Disabilities Act (ADA).

A federal grand jury in Greensboro, N.C., returned an indictment today charging a poultry processor and a plant manager with multiple violations of the Clean Water Act for illegally discharging wastewater from its Raeford, N.C., based facility

Thomas Howard Blue Sr., Thomas Howard Blue Jr. and Judson Hartley Talbert pleaded guilty today in federal court in Florence, S.C., to charges relating to the assault of an African-American man and two white men in December 2007.

The Department filed a brief as a friend of the court in Marlo M., et al. v. Cansler, et al., a community integration case in federal court for the Eastern District of North Carolina.

Howard William Ledford of Hayesville, N.C., was sentenced today in federal court in the Western District of North Carolina to serve one year in prison for illegally selling and transporting wild American ginseng into Georgia.

The Department announced a settlement agreement with Sunlight Inc., doing business as Beauty Smart, of Durham, N.C., to resolve allegations of a pattern or practice of discrimination in recruitment and hiring on the basis of national origin.

The United States has asked a federal court in Columbia, S.C., to permanently bar Dorothy Anderson, d/b/a DL Anderson Tax Service, from preparing federal income tax returns for others.

Norfolk Southern Railway Company has agreed to pay a $4 million penalty to resolve alleged violations of the Clean Water Act (CWA) and hazardous materials laws for a 2005 chlorine spill in Graniteville, S.C.

U.S. District Court Judge R. Bryan Harwell has sentenced three men in Florence, S.C., for their role in terrorizing an African-American man and two Caucasian men and for carjacking.

A 12-person federal jury in Charlotte, N.C., today voted unanimously to impose the death penalty against Alejandro Enrique Ramirez Umana, aka “Wizard,” 25.

A federal district judge in Columbia, S.C., has permanently barred Dorothy Lee Anderson of Hopkins, S.C., from preparing federal tax returns for others.

A federal court in Columbia, S.C., has permanently barred Winston Able of Blythewood, S.C., from preparing federal income tax returns for others.

"I believe our criminal defense system can, and will, become a source of tremendous national pride. I look forward to working with you all in achieving this goal. And I am grateful for your guidance, your engagement, and for your commitment," said Attorney General Holder.

Timothy Christenbury, 47, was sentenced today in Charlotte, N.C., to 72 months in prison and 10 years of supervised release following his prison term for possessing child pornography.

Seven members of the gang known as La Mara Salvatrucha, or MS-13, were sentenced to prison Tuesday for their participation in a racketeering enterprise.

The Justice Department today announced an agreement with Wilson County, N.C., to improve access to all aspects of civic life for persons with disabilities.

A former Kyrgyzstan country manager for a U.S. tobacco company has pleaded guilty for his role in a conspiracy to pay bribes to officials of the Republic of Kyrgyzstan.

A Raleigh, N.C., real estate speculator pleaded guilty to conspiring to rig bids for public real estate foreclosure auctions held in multiple counties in eastern North Carolina.

The United States has sued a Bryson City, N.C., tax return preparer seeking to bar her and her company from preparing federal tax returns for others.

A McCormick, S.C., tax return preparer pleaded guilty today to two counts of aiding and assisting in the preparation of false tax returns.

Rodney K. Justin, a medical doctor from Woodleaf, N.C., was sentenced to three years in prison and ordered to pay over $600,000 in restitution to the Internal Revenue Service (IRS) for obstructing the internal revenue laws and for failing to file tax returns for several years.

Oddie Tribble, a former police officer with the Kershaw County, S.C., Sherriff’s Office, was charged today with violating the civil rights of an arrestee on Aug. 5, 2010.

The Justice Department reached a settlement agreement with the University of South Carolina to resolve an investigation into the university’s policies and procedures related to discrimination and harassment.

The Justice Department today announced that it has reached a settlement agreement with Collins Management Corporation, a forestry products company in Oregon, to resolve allegations that it unlawfully fired and later refused to rehire a lawful permanent resident in violation of the anti-discrimination provision of the Immigration and Nationality Act.

The Justice Department announced today that it has settled its suit against the town of Garner, N.C., and the town’s Board of Adjustment alleging that they violated the Fair Housing Act when refused to allow up to eight men recovering from drug and alcohol addictions to live together as a reasonable accommodation.

A federal jury in Columbia, S.C., convicted Oddie Tribble, 51, a former police officer with the Kershaw County, S.C., Sherriff’s Office, of a civil rights violation for his use of excessive force on a man in his custody on Aug. 5, 2010.

Daniel Patrick Boyd, aka “Saifullah,” 40, pleaded guilty today in federal court in New Bern, N.C., to conspiracy to provide material support to terrorists and conspiracy to murder, kidnap, maim and injure persons in a foreign country.

A federal court has permanently barred Jody S. Ball of Bryson City, N.C., from preparing federal income tax returns for others.

Ugochukwu Enwerem, aka Joseph Smith, was sentenced yesterday in U.S. District Court in Charlotte, N.C., to 108 months in prison for his role in an advance-fee fraud scheme.