Background:

Relatives of patients with bladder cancer have been shown to be at increased risk for kidney, lung, thyroid, and cervical cancer after correcting for smoking-related behaviors that may concentrate in some families. We demonstrate a novel approach to simultaneously assess risks for multiple cancers to identify distinct multicancer configurations (multiple different cancer types that cluster in relatives) surrounding patients with familial bladder cancer.

Background:

New technologies are being developed for early detection of multiple types of cancer simultaneously. To quantify the potential benefit, we estimated reductions in absolute cancer–related deaths that could occur if cancers diagnosed after metastasis (stage IV) were instead diagnosed at earlier stages.

The Klenow fragment, which retains the template-dependent deoxynucleotide polymerizing activity and the 3' -> 5' exonuclease of the holo-enzyme but lacks its powerful 5' -> 3' exonuclease activity, is used to fill recessed 3' termini of dsDNA. In this protocol, fragments suitable as templates for the end-filling reaction are produced by digestion of DNA with an appropriate restriction enzyme. The Klenow enzyme is then used to catalyze the attachment of dNTPs to the recessed 3'-hydroxyl groups.

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.

This protocol is used to determine the concentration of DNase-resistant vector genomes (i.e., packaged in the capsid) in purified recombinant adeno-associated virus (rAAV) preparations. The protocol begins with treatment of the vector stock with DNase I to eliminate unencapsidated AAV DNA or contaminating plasmid DNA. This is followed by a heat treatment to heat-inactivate DNase I, to disrupt the viral capsid, and to release the packaged vector genomes for quantification by real-time polymerase chain reaction (PCR) using a set of standards (linearized plasmid used for vector production) containing known copy numbers. To accomplish high-throughput titration, the primer and probe sets used in real-time PCR are usually designed to target common elements present in most rAAV genomes, such as promoters and poly(A) signals. This strategy significantly reduces the number of PCRs, controls, and turnaround time. Several important controls should be included in the assay as follows: The first two controls should have a known copy number of the rAAV genome plasmid treated or not treated with DNase I. This control tests the effectiveness of DNase treatment. To control for potential cross-contamination between samples during the preparation process, a blank control containing nuclease-free water only should be processed and tested in parallel. A validation vector sample with a known titer should be included in every assay to monitor interassay variability. Finally, for the PCR run, a no-template control (NTC) is included to indicate cross-contamination during PCR setup.

Although ample evidence indicates that immune cell homeostasis is an important prognostic outcome determinant in patients with cancer, few studies have examined whether it also determines cancer risk among initially healthy individuals. We performed a case–cohort study including incident cases of breast (n = 207), colorectal (n = 111), lung (n = 70), and prostate (n = 201) cancer as well as a subcohort (n = 465) within the European Prospective Investigation into Cancer and Nutrition-Heidelberg cohort. Relative counts of neutrophils, monocytes, and lymphocyte sublineages were measured by qRT-PCR. HRs and 95% confidence intervals were used to measure the associations between relative counts of immune cell and cancer risks. When relative counts of immune cell types were taken individually, a significant positive association was observed between relative counts of FOXP3+ regulatory T cells (Tregs) and lung cancer risk, and significant inverse associations were observed between relative CD8+ counts and risks of lung and breast cancer (overall and ER+ subtype). Multivariable models with mutual adjustments across immune markers showed further significant positive associations between higher relative FOXP3+ T-cell counts and increased risks of colorectal and breast cancer (overall and ER− subtype). No associations were found between immune cell composition and prostate cancer risk. These results affirm the relevance of elevated FOXP3+ Tregs and lower levels of cytotoxic (CD8+) T cells as risk factors for tumor development.Significance:This epidemiologic study supports a role for both regulatory and cytotoxic T cells in determining cancer risk among healthy individuals.See related commentary by Song and Tworoger, p. 1801

RING-finger E3 ligases are instrumental in the regulation of inflammatory cascades, apoptosis, and cancer. However, their roles are relatively unknown in TGFβ/SMAD signaling. SMAD3 and its adaptors, such as β2SP, are important mediators of TGFβ signaling and regulate gene expression to suppress stem cell–like phenotypes in diverse cancers, including hepatocellular carcinoma (HCC). Here, PJA1, an E3 ligase, promoted ubiquitination and degradation of phosphorylated SMAD3 and impaired a SMAD3/β2SP-dependent tumor-suppressing pathway in multiple HCC cell lines. In mice deficient for SMAD3 (Smad3+/−), PJA1 overexpression promoted the transformation of liver stem cells. Analysis of genes regulated by PJA1 knockdown and TGFβ1 signaling revealed 1,584 co-upregulated genes and 1,280 co-downregulated genes, including many implicated in cancer. The E3 ligase inhibitor RTA405 enhanced SMAD3-regulated gene expression and reduced growth of HCC cells in culture and xenografts of HCC tumors, suggesting that inhibition of PJA1 may be beneficial in treating HCC or preventing HCC development in at-risk patients.Significance: These findings provide a novel mechanism regulating the tumor suppressor function of TGFβ in liver carcinogenesis.

While immuno-oncology has made significant advances in activating local tumor immune responses, leading to improved outcomes, the role of systemic immunity in cancer incidence remains poorly understood. Le Cornet and colleagues prospectively studied circulating immune cells quantified by DNA methylation markers in relation to incidence of breast, colorectal, lung, and prostate cancer among initially healthy individuals. A positive association with cancer risk was observed for higher FOXP3+ T-cell–mediated immune tolerance and lower CD8+ T-cell–mediated cytotoxicity. Further studies of systemic immunity in cancer development are crucial to identify novel prediction markers and interventional targets for cancer immunoprevention.See related article by Le Cornet et al., p. 1885

An annual report released by the Ministry of Construction (MoC) at a press conference on Monday showed housing prices in the two mảo cities Hanoi and Ho Chi Minh (HCMC) rose slightly in the third quarter (Q3) of this year.

The constantly increasing number of new real estate projects which have been implemented in the Mekong Delta region has led to the rising land price and strong fluctuation in the local property market.

We spoke with industry experts to identify what’s preventing developers from fully going green – and it all boils down to lack of finances.

As they implement stricter measures and distribute millions worth of donations to communities in need.

Many entrepreneurs become so excited about launching their new business venture that they fail to find the right location for it. This is one of the first steps that can be very critical to your success in future.

To ensure that you can afford for your living expenditures, you should not spend more than 30-40% of income on housing.

Doanh số bán các căn hộ trị giá từ 10 triệu đô la Singapore (SGD), tương đương 7,3 triệu USD trở lên, đã chạm mức cao nhất trong 11 năm qua. Nhu cầu tìm kiếm tài sản “trú ẩn” của các triệu phú Trung Quốc được cho là nguyên nhân chính thúc đẩy sự tăng trưởng ấn tượng này.

Theo báo cáo của Colliers International, các chủ đầu tư văn phòng tại khu trung tâm Singapore không ngừng nâng giá thuê trong suốt 9 quý liên tục, khiến người thuê bất bình. Những văn phòng này chủ yếu là văn phòng hạng A, nằm trong các khu kinh doanh sầm uất nhất Singapore.

Ngân hàng trung ương Singapore gần đây đã đưa ra lời cảnh báo trước tình trạng “ế hàng” của thị trường bất động sản cũng như sự sụt giảm của thị trường lao động. Giá bất động sản để ở trước đó giảm mạnh sau khi chính phủ thực hiện các biện pháp kiểm soát tài sản từ tháng 7 năm ngoái, nhưng gần đây đã bắt đầu tăng trở lại.

Narsingh Jayanti 2020: नरसिंह जयंती भगवान नरसिंह जी का जन्मोत्सव है। हिन्दू पंचांग के अनुसार, भगवान नरसिंह जी का अवतरण वैशाख शुक्ल पक्ष की चतुर्दशी तिथि के दिन हुआ था। इस वर्ष यह तिथि 6 मई को पड़ रही है। इसलिए नरसिंह जयंती 6 मई को मनाई जाएगी।

मास वैशाख कृतिका युत, हरण मही को भार। शुक्ल चतुर्दशी सोम दिन, लियो नरसिंह अवतार।।

उदयरवि सहस्रद्योतितं रूक्षवीक्षं प्रळय जलधिनादं कल्पकृद्वह्नि वक्त्रम् | सुरपतिरिपु वक्षश्छेद रक्तोक्षिताङ्गं प्रणतभयहरं तं नारसिंहं नमामि ||

भक्त प्रह्राद की रक्षा के लिए भगवान विष्णु ने नरसिंह अवतार लिया था। नरसिंह जयंती के दिन भगवान नरसिंह की उपासना करने से सभी संकटों से मुक्ति मिलती है।

Nintendo has released its latest hardware and software figures for the Nintendo Switch and Nintendo 3DS through March 31, 2020. Shipments figures for the Nintendo Switch reached 55.77 million units, while the Nintendo 3DS hit 75.77 million units shipped. As for lifetime software 356.24 million Switch games have been shipped and 383.11 million 3DS games. 

For the quarter Nintendo shipped 3.28 million Switch units and 45.59 million Switch games, as well as 0.07 million 3DS units and 0.89 million 3DS games. 

Nintendo forecasts it will ship 19 million Switch units in the fiscal year ending March 31, 2021.

Here are the top 10 best-selling Switch first-party titles:

1. Mario Kart 8 Deluxe – 24.77 million
2. Super Smash Bros. Ultimate – 18.84 million
3. The Legend of Zelda: Breath of the Wild – 17.41 million
4. Super Mario Odyssey – 17.41 million
5. Pokemon Sword / Pokemon Shield – 17.37 million
6. Pokemon: Let’s Go, Pikachu! / Pokemon: Let’s Go, Eevee! – 11.97 million
7. Animal Crossing: New Horizons – 11.77 million (first 11 days) / 13.41 million (first six weeks)
8. Splatoon 2 – 10.13 million
9. Super Mario Party – 10.10 million
10. New Super Mario Bros. U Deluxe – 6.60 million

A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel dedicated to gaming Let's Plays and tutorials. You can contact the author at wdangelo@vgchartz.com or on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/443417/switch-shipments-reach-5577-million-units-as-of-march-31-animal-crossing-new-horizons-sells-12-million/

QR codes, tracking apps and drones at toll booths are just some of the tech tools China is deploying to monitor the spread of the new coronavirus

Robots are being developed to help with tasks like fixing the sea cages where fish are farmed, and their size seems to be all that affects how the fish react

Strange as it may sound, Animal Crossing: New Horizons feels like where Breath of the Wild should have ended up gameplay-wise.

As well as announcing reminders to stay away from each other, the robots also estimate how many people are in the park at any given time.

The Milky Way ate another galaxy called Gaia-Enceladus, and the waves passing through a star have shown us that it happened at most 11.6 billion years ago

The leading hypothesis for how the moon formed involves a collision between a Mars-sized object and Earth that would have boiled away elements like carbon, making its discovery on the moon a mystery

The overlooked epicenter of the Covid-19 pandemic is our nation's nursing homes, veterans' homes, and other long-term care facilities.

Long before NLP became a hot field in AI, people devised rules and machines to manipulate language

A new contest aims to help first responders leverage computer vision algorithms and drone imagery during a search

Record low bond yields are pushing superannuation funds and insurers into alternative investments.

Advertising spending contributes about $40 billion a year to the Australian economy, or 2 per cent of GDP.

Xenosaga Chronicles 2 is here. Did you get a switch just for it? Chris and Alex talk through their experiences. Johnathan, meanwhile, has been delving...

From tiny sunglasses to leather coats, the film’s costume designer Kym Barrett writes about why the film’s look feels so relevant in our uncertain world

• Read more from the spring/summer 2020 edition of The Fashion, our biannual style supplement

I never thought The Matrix would have the impact it has had on fashion. But from long leather coats to so-called “Matrix-style” sunglasses, the costumes I designed in the 90s continue to have influence to this day.

Part of the reason they are still in the ether is because they were so iconic. The silhouettes, for instance, had to be instantly recognisable so that viewers could tell who each character was, even in the dark. All of the costumes are fairly immune to period, which is what makes them relatable, even now.

Brighten up WFH with colourful loungewear to lighten the mood