ISLAMABAD: The Supreme Court Friday expected that the caretaker government in Gilgit-Baltistan will comprise highly respected persons with proven integrity, impartiality, and competence and will...

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ISLAMABAD: The Supreme Court Friday expected that the caretaker government in Gilgit-Baltistan will comprise highly respected persons with proven integrity, impartiality, and competence and will...

[[ This is a content summary only. Visit my website for full links, other content, and more! ]]

ISLAMABAD: The Supreme Court Friday expected that the caretaker government in Gilgit-Baltistan will comprise highly respected persons with proven integrity, impartiality, and competence and will...

[[ This is a content summary only. Visit my website for full links, other content, and more! ]]

For quality evaluations of international development projects and programs to lead to better results, they need to be influential.

Singapore’s carbon tax is designed to maximize green investments while minimizing negative effects on the overall economy.

These charts illustrate how Asian and global stock markets reacted to the COVID-19 pandemic, with market reaction closely following local outbreaks and then moving in unison with global markets amid other shocks.

Benin drops 17 places in the 2020 World Press Freedom Index, following the withdrawal from a key document of the African Charter of Human and People's Rights.

Approved project 54061-001 in Sri Lanka.

Capitedge India Investment Advisory, a realty fund and asset management firm floated by six former members of Indian realty team of American banking giant Wells Fargo, is coming out with a residential properties-focused fund in India. This would mark its first fresh fundraising exercise after floating an independent investment advisory firm, which is also managing the remaining assets of Wells Fargo after it shut operations in the country last year. While the founding partners are closely associated in operations, Hiral Soni is driving the domestic fundraise and investment strategy, as per the company website. She was previously with Marvel Realtors and had later also set up a boutique investment banking […]

East Asia is setting the pace for the recent trend in regional and interregional integration, which is associated with multilateral infrastructure connectivity initiatives.

East Asia is setting the pace for the recent trend in regional and interregional integration, which is associated with multilateral infrastructure connectivity initiatives.

AN3444 Driving LEDs with Constant Current and Sequential Linear LED Drivers

HOWRAH: With an eye on boosting revenue, the Howrah Municipal Corporation announced a partial waiver for property and commercial tax on Tuesday. Under the waiver scheme, no penalty or interest need to be paid. The KMC has already enforced such a scheme and has benefited greatly, said Howrah mayor Rathin Chakraborty. He said the last board, controlled by the Left Front, bungled in tax collection, resulting in tax default of around Rs 200 crore. “The state is supporting us, but we must be self-sufficient. The tax outstanding will be collected without burdening civilians,” the mayor added. http://timesofindia.indiatimes.com/city/kolkata/Howrah-Municipal-Corporation-announces-partial-waiver-of-property-and-commercial-tax/articleshow/31431111.cms

According to a study by India Ratings, lack of credit availability and ongoing economic slowdown in India due to the coronavirus pandemic could lead to the residential sector witnessing weak demand in the fiscal year 2020-21.  Residential demand could remain muted in the next financial year, 2020-21 due to the increasing risks to India’s growth in case the economic impact of coronavirus continues beyond the first quarter.   Moreover, the housing sector faces a liquidity crunch and refinancing challenges due to increasing uncertainty over the availability of credit in the market, coupled with poor demand. This is in the backdrop of the recent meltdown in the financial market and rising risk […]

By Dr. Cristina Bettencourt, Head of HARMAN University   At HARMAN, we owe every degree of our success to our talented and dedicated employees. While we already have extraordinary talent across all of our operations, we never stop trying to improve by...

NORTHRIDGE, Calif.—HARMAN Professional Solutions, the global leader in audio, video, lighting and control systems, today announced the new AKG Podcaster Essentials bundle at the 2020 NAMM show in Anaheim, California and the 2020 CES shows in Las Vegas,...

CES 2020 – LAS VEGAS, Nev. – January 6, 2020 – HARMAN, a wholly-owned subsidiary of Samsung Electronics Co., Ltd., focused on connected technologies and solutions for automotive, consumer and enterprise markets, today unveiled a new ADAS use case, called...

The grunts, groans and the sound of pulsing music and crashing weights has returned to some of Beijing's gyms after being closed for nearly three months due to the coronavirus outbreak. Ciara Lee reports.

A fresh look at the world’s oldest religious texts suggests ancient Egyptians saw the sky as a water-filled iron container from which chunks fell to Earth as meteorites

Many ancient monuments are claimed to be aligned to celestial phenomena, but we now have the first statistical evidence this is the case for the Egyptian pyramids

The story of how gin and tonic came together fizzes with adventure, discovery, imperial ambition, biopiracy and a generous splash of fake news

London's High Court on Friday threw out part of a claim brought by Meghan, Britain's Duchess of Sussex, against a tabloid newspaper for breaching her privacy, ruling that it had not acted dishonestly. Lauren Anthony reports.

The grunts, groans and the sound of pulsing music and crashing weights has returned to some of Beijing's gyms after being closed for nearly three months due to the coronavirus outbreak. Ciara Lee reports.

A long-standing hypothesis suggests the BCG vaccine also serves to generally enhance the immune system, meaning it could protect against covid-19, and trials are under way to find out

A fresh look at the world’s oldest religious texts suggests ancient Egyptians saw the sky as a water-filled iron container from which chunks fell to Earth as meteorites

Many ancient monuments are claimed to be aligned to celestial phenomena, but we now have the first statistical evidence this is the case for the Egyptian pyramids

Title: AHA News: Hearing Loss and the Connection to Alzheimer's Disease, Dementia
Category: Health News
Created: 5/6/2020 12:00:00 AM
Last Editorial Review: 5/7/2020 12:00:00 AM

Title: Martial Arts Training May Save Seniors' Hips
Category: Health News
Created: 4/23/2010 10:10:00 AM
Last Editorial Review: 4/26/2010 12:00:00 AM

Title: Test Spots Potential Organ Donors Among Coma Patients
Category: Health News
Created: 4/26/2010 4:10:00 PM
Last Editorial Review: 4/27/2010 12:00:00 AM

Title: Is Drinking Wine a Key to Antiaging?
Category: Health News
Created: 4/28/2010 9:36:00 AM
Last Editorial Review: 4/28/2010 9:36:34 AM

Title: Mediterranean Diet Might Help Stave Off Dementia
Category: Health News
Created: 4/29/2013 4:35:00 PM
Last Editorial Review: 4/30/2013 12:00:00 AM

Title: General Anesthesia Not Linked to Raised Risk for Dementia
Category: Health News
Created: 5/1/2013 12:35:00 PM
Last Editorial Review: 5/2/2013 12:00:00 AM

Title: Loving, Supportive Kids May Help Lower Seniors' Dementia Risk
Category: Health News
Created: 5/2/2017 12:00:00 AM
Last Editorial Review: 5/3/2017 12:00:00 AM

Title: Mid-Life Stresses May Be Tied to Late-Life Dementia Risk
Category: Health News
Created: 4/30/2018 12:00:00 AM
Last Editorial Review: 5/1/2018 12:00:00 AM

Title: Some Reasons to Work With a Dietitian
Category: Health News
Created: 5/2/2018 12:00:00 AM
Last Editorial Review: 5/2/2018 12:00:00 AM

Title: Newly Discovered Illness May Cause Nearly 1 in 5 Dementias, Experts Say
Category: Health News
Created: 4/30/2019 12:00:00 AM
Last Editorial Review: 5/1/2019 12:00:00 AM

Title: AHA News: Essential Advice for Stressed-Out Essential Workers
Category: Health News
Created: 4/24/2020 12:00:00 AM
Last Editorial Review: 4/27/2020 12:00:00 AM

Title: New Initiative to Study Coronavirus Genome
Category: Health News
Created: 5/1/2020 12:00:00 AM
Last Editorial Review: 5/1/2020 12:00:00 AM

Title: Heart Drug Combos Might Also Lower Your Dementia Risk: Study
Category: Health News
Created: 3/13/2020 12:00:00 AM
Last Editorial Review: 3/16/2020 12:00:00 AM

Title: Study Ties Brain Inflammation to Several Types of Dementia
Category: Health News
Created: 3/18/2020 12:00:00 AM
Last Editorial Review: 3/18/2020 12:00:00 AM

Title: Daily Aspirin Won't Stop Dementia, Study Finds
Category: Health News
Created: 3/25/2020 12:00:00 AM
Last Editorial Review: 3/26/2020 12:00:00 AM

Title: Dirty Air Might Raise Your Odds for Dementia
Category: Health News
Created: 3/31/2020 12:00:00 AM
Last Editorial Review: 4/1/2020 12:00:00 AM

Title: Which Foods Might Reduce Your Odds for Dementia?
Category: Health News
Created: 4/14/2020 12:00:00 AM
Last Editorial Review: 4/14/2020 12:00:00 AM

Title: Gynecomastia (Enlarged Male Breasts)
Category: Diseases and Conditions
Created: 10/7/2009 12:00:00 AM
Last Editorial Review: 11/14/2019 12:00:00 AM

Title: lopinavir and ritonavir (Kaletra): Potential COVID-19 Drug
Category: Medications
Created: 3/12/2001 12:00:00 AM
Last Editorial Review: 4/8/2020 12:00:00 AM

Title: What Is a Partial Gastrectomy?
Category: Procedures and Tests
Created: 5/7/2020 12:00:00 AM
Last Editorial Review: 5/7/2020 12:00:00 AM

Title: azithromycin (Zithromax): Potential COVID-19 Combo Drug
Category: Medications
Created: 12/31/1997 12:00:00 AM
Last Editorial Review: 3/30/2020 12:00:00 AM

The development of efficacious therapies targeting metastatic spread of breast cancer to the brain represents an unmet clinical need. Accordingly, an improved understanding of the molecular underpinnings of central nervous system spread and progression of breast cancer brain metastases (BCBM) is required. In this study, the clinical burden of disease in BCBM was investigated, as well as the role of aldehyde dehydrogenase 1A3 (ALDH1A3) in the metastatic cascade leading to BCBM development. Initial analysis of clinical survival trends for breast cancer and BCBM determined improvement of breast cancer survival rates; however, this has failed to positively affect the prognostic milestones of triple-negative breast cancer (TNBC) brain metastases (BM). ALDH1A3 and a representative epithelial–mesenchymal transition (EMT) gene signature (mesenchymal markers, CD44 or Vimentin) were compared in tumors derived from BM, lung metastases (LM), or bone metastases (BoM) of patients as well as mice after injection of TNBC cells. Selective elevation of the EMT signature and ALDH1A3 were observed in BM, unlike LM and BoM, especially in the tumor edge. Furthermore, ALDH1A3 was determined to play a role in BCBM establishment via regulation of circulating tumor cell adhesion and migration phases in the BCBM cascade. Validation through genetic and pharmacologic inhibition of ALDH1A3 via lentiviral shRNA knockdown and a novel small-molecule inhibitor demonstrated selective inhibition of BCBM formation with prolonged survival of tumor-bearing mice. Given the survival benefits via targeting ALDH1A3, it may prove an effective therapeutic strategy for BCBM prevention and/or treatment.

Physical and chemical DNA-damaging agents are used widely in the treatment of cancer. Double-strand break (DSB) lesions in DNA are the most deleterious form of damage and, if left unrepaired, can effectively kill cancer cells. DNA-dependent protein kinase (DNA-PK) is a critical component of nonhomologous end joining (NHEJ), one of the two major pathways for DSB repair. Although DNA-PK has been considered an attractive target for cancer therapy, the development of pharmacologic DNA-PK inhibitors for clinical use has been lagging. Here, we report the discovery and characterization of a potent, selective, and orally bioavailable DNA-PK inhibitor, M3814 (peposertib), and provide in vivo proof of principle for DNA-PK inhibition as a novel approach to combination radiotherapy. M3814 potently inhibits DNA-PK catalytic activity and sensitizes multiple cancer cell lines to ionizing radiation (IR) and DSB-inducing agents. Inhibition of DNA-PK autophosphorylation in cancer cells or xenograft tumors led to an increased number of persistent DSBs. Oral administration of M3814 to two xenograft models of human cancer, using a clinically established 6-week fractionated radiation schedule, strongly potentiated the antitumor activity of IR and led to complete tumor regression at nontoxic doses. Our results strongly support DNA-PK inhibition as a novel approach for the combination radiotherapy of cancer. M3814 is currently under investigation in combination with radiotherapy in clinical trials.

ABSTRACT

The synergy between Mycobacterium tuberculosis and human immunodeficiency virus-1 (HIV-1) interferes with therapy and facilitates the pathogenesis of both human pathogens. Fundamental mechanisms by which M. tuberculosis exacerbates HIV-1 infection are not clear. Here, we show that exosomes secreted by macrophages infected with M. tuberculosis, including drug-resistant clinical strains, reactivated HIV-1 by inducing oxidative stress. Mechanistically, M. tuberculosis-specific exosomes realigned mitochondrial and nonmitochondrial oxygen consumption rates (OCR) and modulated the expression of host genes mediating oxidative stress response, inflammation, and HIV-1 transactivation. Proteomics analyses revealed the enrichment of several host factors (e.g., HIF-1α, galectins, and Hsp90) known to promote HIV-1 reactivation in M. tuberculosis-specific exosomes. Treatment with a known antioxidant—N-acetyl cysteine (NAC)—or with inhibitors of host factors—galectins and Hsp90—attenuated HIV-1 reactivation by M. tuberculosis-specific exosomes. Our findings uncover new paradigms for understanding the redox and bioenergetics bases of HIV-M. tuberculosis coinfection, which will enable the design of effective therapeutic strategies.

IMPORTANCE Globally, individuals coinfected with the AIDS virus (HIV-1) and with M. tuberculosis (causative agent of tuberculosis [TB]) pose major obstacles in the clinical management of both diseases. At the heart of this issue is the apparent synergy between the two human pathogens. On the one hand, mechanisms induced by HIV-1 for reactivation of TB in AIDS patients are well characterized. On the other hand, while clinical findings clearly identified TB as a risk factor for HIV-1 reactivation and associated mortality, basic mechanisms by which M. tuberculosis exacerbates HIV-1 replication and infection remain poorly characterized. The significance of our research is in identifying the role of fundamental mechanisms such as redox and energy metabolism in catalyzing HIV-M. tuberculosis synergy. The quantification of redox and respiratory parameters affected by M. tuberculosis in stimulating HIV-1 will greatly enhance our understanding of HIV-M. tuberculosis coinfection, leading to a wider impact on the biomedical research community and creating new translational opportunities.