Imagine zipping down a 750-foot zipline over your private lake, then taking in the beautiful Colorado views from the comfort of the expansive front porch of your log home.

The newly launched ‘1093 helpline service’ of the Sindh Local Government Department has been providing counselling service to around 50 people on a daily basis who are suffering from various psychological issues due to the ongoing coronavirus crisis in the country, said Sindh Local...

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ADB today approved an additional $500 million loan to bolster the efforts of the Government of Bangladesh to manage the impact of the novel coronavirus disease (COVID-19) pandemic on the country’s economy and the public health.

Over 50 flights are scheduled to return stranded Lebanese citizens in the third phase of citizen repatriation set to begin May 14, Middle East Airlines said in a statement Friday.

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ADB has approved $50 million in loan and grant financing to help the Government of the Kyrgyz Republic mitigate the significant negative health, social, and economic impacts of the novel coronavirus disease (COVID-19) pandemic.

ADB today approved an additional $500 million loan to bolster the efforts of the Government of Bangladesh to manage the impact of the novel coronavirus disease (COVID-19) pandemic on the country’s economy and the public health.

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Iran warned Saturday that coronavirus infections were rising in the southwest despite falls in other regions, as it announced more than 1,500 new confirmed cases.

ADB has approved $50 million in loan and grant financing to help the Kyrgyz Republic mitigate the health and socioeconomic impact of COVID-19 pandemic.

АБР утвердил пакет финансирования на сумму 50 млн. долл. США для оказания помощи Кыргызской Республике смягчить последствия COVID-19 на здоровье и социально-экономические аспекты.

MOST150 Technology to Control the Infotainment System on Volvo Cars’ Second-Generation XC60 SUV

Microchip Delivers 50 Millionth MOST® Technology 50 Mbps Automotive Intelligent Network Interface Controller

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AT25010B/AT25020B/AT25040B SPI Automotive Temperature Serial EEPROM Data Sheet

NEW DELHI: Realty firm Ambience today said it will invest about Rs 1,950 crore over the next four years to develop two luxury housing projects in Gurgaon and Noida. The Delhi-based company will develop over 1,030 apartments in these two projects launched today. Ambience has presence in Delhi and Gurgaon property markets. It is developing a 150-acre project ‘Ambience Island’ in Gurgaon that comprises premium homes, ‘Leela Ambience’ hotel with over 400 keys and a huge shopping mall. In Delhi, it has a ‘Kempinski Ambience’ hotel comprising 480 keys and a shopping mall at Vasant Kunj. “We are coming up two new projects in Noida and Gurgaon. We are entering […]

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Bangalore/Mumbai: HDFC Property Fund, the private equity arm of Housing Development Finance Corp. Ltd, has raised $250 million (around `1,500 crore today) through an offshore fund. It hopes to raise another $150 million by the end of the year, said a person directly familiar with the development who did not want to be named. On Friday, HDFC Property Fund informed the BSE that it had raised the capital through its second international fund, saying “the recently closed fund will focus on investing primarily in residential property developments in major cities across India”. The cumulative assets under management now exceed $1 billion, the statement added. The new fund, which started raising […]

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ATMX150RHA Power-supply sequencing

Telangana government has plans to infuse a sum of Rs 50,000 crore to uplift the infra status in Hyderabad in the next five years. KT Rama Rao, Minister for Urban Development and Municipal Affairs (MA&UD) has shared that the fund would be utilised for the development of the Hyderabad Urban Agglomeration area. A corpus of Rs 50,000 crore is being readied by the Telangana government, which would go into the development of the Hyderabad Urban Agglomeration (HUA) region. KT Rama Rao, Minister for Urban Development and Municipal Affairs (MA&UD) has shared the information. HUA region comprises the core of the city as well as its outskirts falling within the Outer […]

MUMBAI: US private equity firm Kohlberg Kravis Roberts & Co has made its entry in the country’s real estate sector by finalising investments of Rs 750 crore in two property projects. KKR has struck a structured debt transaction for Rs 400 crore for the Bhartiya Group’s integrated township project in Bangalore, two people with direct knowledge of the transactions said. It also agreed to provide a Rs 350 crore structured loan to the Wadhwa Group’s luxury home project in west central Mumbai, they said. The group will use the money to repay other lenders of the project, where the cost of apartments ranges from Rs 1.5 crore to Rs 10 […]

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NEW DELHI: Realty firm Logix group plans to raise Rs 250 crore from foreign investors for the development of its ongoing mixed-use commercial project in Noida. The company is developing this commercial project at an investment of Rs 1,000 crore and is looking to raise FDI to complete this project. The 6-acre project ‘Noida City Center’ includes a 7 lakh sq ft shopping mall, 2.5 lakh sq ft office towers, two hotels with combined 400 rooms and 100 service apartments. “Total project cost of this commercial project is Rs 1,000 crore,” Logix group CMD Shakti Nath said. The investments are largely met through internal accruals, he said, adding that the […]

A 50-year-old maths problem has finally been solved, and it shows that even an infinitely large lottery ticket could not contain every winning solution

In 2012, mathematician Shinichi Mochizuki produced a proof claiming to solve the long-standing ABC conjecture, but no one understood it. Most mathematicians still don't, but it will now be published in a journal

The genomes of 2514 new viruses have been identified in DNA recovered from human and animal cells, many of them belonging to wholly new families

The age of a whale shark can be determined by dating the rings of growth in their cartilage, a method that has confirmed that these animals can live for at least 50 years

A piece of string found in a cave in France is the oldest ever discovered and shows that Neanderthals knew how to twist fibres together to make cords

Coronavirus will overshadow Earth Day's golden anniversary, but the movement's successes are worth celebrating, says Gary Paul Nabhan

Title: 50 Years of Data Confirm Benefit of Antipsychotics
Category: Health News
Created: 5/3/2012 11:00:00 AM
Last Editorial Review: 5/3/2012 12:00:00 AM

Title: After Age 50, Yearly Eye Checks May Catch Common Cause of Vision Loss
Category: Health News
Created: 4/28/2018 12:00:00 AM
Last Editorial Review: 4/30/2018 12:00:00 AM

Title: NIH Launches $500 Million Contest to Produce Best COVID-19 Test
Category: Health News
Created: 4/29/2020 12:00:00 AM
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Title: Dangerously Hot Days for U.S. Farm Workers Could Double by 2050
Category: Health News
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Legionella pneumophila, the etiological agent of Legionnaires’ disease, employs an arsenal of hundreds of Dot/Icm-translocated effector proteins to facilitate replication within eukaryotic phagocytes. Several effectors, called metaeffectors, function to regulate the activity of other Dot/Icm-translocated effectors during infection. The metaeffector Lpg2505 is essential for L. pneumophila intracellular replication only when its cognate effector, SidI, is present. SidI is a cytotoxic effector that interacts with the host translation factor eEF1A and potently inhibits eukaryotic protein translation by an unknown mechanism. Here, we evaluated the impact of Lpg2505 on SidI-mediated phenotypes and investigated the mechanism of SidI function. We determined that Lpg2505 binds with nanomolar affinity to SidI and suppresses SidI-mediated inhibition of protein translation. SidI binding to eEF1A and Lpg2505 is not mutually exclusive, and the proteins bind distinct regions of SidI. We also discovered that SidI possesses GDP-dependent glycosyl hydrolase activity and that this activity is regulated by Lpg2505. We have therefore renamed Lpg2505 MesI (metaeffector of SidI). This work reveals novel enzymatic activity for SidI and provides insight into how intracellular replication of L. pneumophila is regulated by a metaeffector.

Respiratory syncytial virus (RSV) is an enveloped RNA virus which is responsible for approximately 80% of lower respiratory tract infections in children. Current lines of evidence have supported the functional involvement of long noncoding RNA (lncRNA) in many viral infectious diseases. However, the overall biological effect and clinical role of lncRNAs in RSV infection remain unclear. In this study, lncRNAs related to respiratory virus infection were obtained from the lncRNA database, and we collected 144 clinical sputum specimens to identify lncRNAs related to RSV infection. Quantitative PCR (qPCR) detection indicated that the expression of lncRNA negative regulator of antiviral response (NRAV) in RSV-positive patients was significantly lower than that in uninfected patients, but lncRNA psoriasis-associated non-protein coding RNA induced by stress (PRINS), nuclear paraspeckle assembly transcript 1 (NEAT1), and Nettoie Salmonella pas Theiler’s (NeST) showed no difference in vivo and in vitro. Meanwhile, overexpression of NRAV promoted RSV proliferation in A549 and BEAS-2B cells, and vice versa, indicating that the downregulation of NRAV was part of the host antiviral defense. RNA fluorescent in situ hybridization (FISH) confirmed that NRAV was mainly located in the cytoplasm. Through RNA sequencing, we found that Rab5c, which is a vesicle transporting protein, showed the same change trend as NRAV. Subsequent investigation revealed that NRAV was able to favor RSV production indirectly by sponging microRNA miR-509-3p so as to release Rab5c and facilitate vesicle transportation. The study provides a new insight into virus-host interaction through noncoding RNA, which may contribute to exploring potential antivirus targets for respiratory virus.

IMPORTANCE The mechanism of interaction between RSV and host noncoding RNAs is not fully understood. In this study, we found that the expression of long noncoding RNA (lncRNA) negative regulator of antiviral response (NRAV) was reduced in RSV-infected patients, and overexpression of NRAV facilitated RSV production in vitro, suggesting that the reduction of NRAV in RSV infection was part of the host antiviral response. We also found that NRAV competed with vesicle protein Rab5c for microRNA miR509-3p in cytoplasm to promote RSV vesicle transport and accelerate RSV proliferation, thereby improving our understanding of the pathogenic mechanism of RSV infection.

Recently, abundant evidence has clarified that long noncoding RNAs (lncRNAs) play an oncogenic or anticancer role in the tumorigenesis and development of diverse human cancers. Described as a crucial regulator in some cancers, MIR22HG has not yet been studied in laryngocarcinoma and therefore the underlying regulatory role of MIR22HG in laryngocarcinoma is worth detecting. In this study, MIR22HG expression in laryngocarcinoma cells was confirmed to be downregulated, and upregulated MIR22HG expression led to suppressive effects on laryngocarcinoma cell proliferation and migration. Molecular mechanism assays revealed that MIR22HG sponges miR-5000-3p in laryngocarcinoma cells. Besides, decreased expression of miR-5000-3p suppressed laryngocarcinoma cell proliferation and migration. Moreover, the FBXW7 gene was reported to be a downstream target gene of miR-5000-3p in laryngocarcinoma cells. More importantly, rescue assays verified that FBXW7 depletion or miR-5000-3p upregulation countervailed the repressive effects of MIR22HG overexpression on laryngocarcinoma progression. In addition, E2F6 was proved to be capable of inhibiting MIR22HG transcription in laryngocarcinoma cells. To sum up, E2F6-induced downregulation of MIR22HG promotes laryngocarcinoma progression through the miR-5000-3p/FBXW7 axis.

Drug-induced liver injury (DILI) is a global medical problem. The risk of DILI is often related to expression and activities of drug-metabolizing enzymes, especially cytochrome P450s (P450s). However, changes on expression and activities of P450s after DILI have not been determined. The aim of this study is to fill this knowledge gap. Acetaminophen (APAP) was used as a model drug to induce DILI in C57BL/6J mice at different ages of days 10 (infant), 22 (child), and 60 (adult). DILI was assessed by levels of alanine aminotransferase and aspartate aminotransferase in plasma with a confirmation by H&E staining on liver tissue sections. The expression of selected P450s at mRNA and protein levels was measured by real-time polymerase chain reaction and liquid chromatography–tandem mass spectrometry, respectively. The activities of these P450s were determined by the formation of metabolites from probe drugs for each P450 using ultraperformance liquid chromatography–quadrupole time of flight mass spectrometry. DILI was induced at mild to severe levels in a dose-dependent manner in 200, 300, and 400 mg/kg APAP-treated groups at child and adult ages, but not at the infant age. Significantly decreased expression at mRNA and protein levels as well as enzymatic activities of CYP2E1, 3A11, 1A2, and 2C29 were found at child and adult ages. Adult male mice were more susceptible to APAP-induced liver injury than female mice with more decreased expression of P450s. These results suggest that altered levels of P450s in livers severely injured by drugs may affect the therapeutic efficacy of drugs, which are metabolized by P450s, more particularly for males.

PF-05089771 is an aryl sulfonamide Nav1.7 channel blocker that binds to the inactivated state of Nav1.7 channels with high affinity but binds only weakly to channels in the resting state. Such aryl sulfonamide Nav1.7 channel blockers bind to the extracellular surface of the S1-S4 voltage-sensor segment of homologous Domain 4, whose movement is associated with inactivation. This binding site is different from that of classic sodium channel inhibitors like lidocaine, which also bind with higher affinity to the inactivated state than the resting state but bind at a site within the pore of the channel. The common dependence on gating state with distinct binding sites raises the possibility that inhibition by aryl sulfonamides and by classic local anesthetics might show an interaction mediated by their mutual state dependence. We tested this possibility by examining the state-dependent inhibition by PF-05089771 and lidocaine of human Nav1.7 channels expressed in human embryonic kidney 293 cells. At –80 mV, where a small fraction of channels are in an inactivated state under drug-free conditions, inhibition by PF-05089771 was both enhanced and speeded in the presence of lidocaine. The results suggest that lidocaine binding to the channel enhances PF-05089771 inhibition by altering the equilibrium between resting states (with D4S4 in the inner position) and inactivated states (with D4S4 in the outer position). The gating state–mediated interaction between the compounds illustrates a principle applicable to many state-dependent agents.

1q21 amplification is an important prognostic marker in multiple myeloma. In this study we identified that IL6R (the interleukin-6 membrane receptor) and ADAR1 (an RNA editing enzyme) are critical genes located within the minimally amplified 1q21 region. Loss of individual genes caused suppression to the oncogenic phenotypes, the magnitude of which was enhanced when both genes were concomitantly lost. Mechanistically, IL6R and ADAR1 collaborated to induce a hyper-activation of the oncogenic STAT3 pathway. High IL6R confers hypersensitivity to interleukin-6 binding, whereas, ADAR1 forms a constitutive feed-forward loop with STAT3 in a P150-isoform-predominant manner. In this respect, ADAR1-P150 acts as a direct transcriptional target for STAT3 and this STAT3-induced-P150 in turn directly interacts with and stabilizes the former protein, leading to a larger pool of proteins acting as oncogenic transcription factors for pro-survival genes. The importance of both IL6R and ADAR1-P150 in STAT3 signaling was further validated when concomitant knockdown of both genes impeded IL6-induced-STAT3 pathway activation. Clinical evaluation of various datasets of myeloma patients showed that low expression of either one or both genes was closely associated with a compromised STAT3 signature, confirming the involvement of IL6R and ADAR1 in the STAT3 pathway and underscoring their essential role in disease pathogenesis. In summary, our findings highlight the complexity of the STAT3 pathway in myeloma, in association with 1q21 amplification. This study therefore reveals a novel perspective on 1q21 abnormalities in myeloma and a potential therapeutic target for this cohort of high-risk patients.

Background:

Early diagnosis can significantly reduce colorectal cancer deaths. We sought to identify serum PIWI-interacting RNAs (piRNAs) that could serve as sensitive and specific noninvasive biomarkers for early colorectal cancer detection.

Adeno-associated virus (AAV) recombinants are currently the vector of choice for many gene therapy applications. As experimental therapies progress to clinical trials, the need to characterize recombinant adeno-associated viruses (rAAVs) accurately and reproducibly increases. Accurate determination of rAAV infectious titer is important for determining the activity of each vector lot and for ensuring lot-to-lot consistency. The following protocol developed in our laboratory uses a 96-well TCID₅₀ format and quantitative polymerase chain reaction (qPCR) detection for the determination of rAAV infectious titer.