Incorporation of ribonucleotides into DNA can severely diminish genome integrity. However, how ribonucleotides instigate DNA damage is poorly understood. In DNA, they can promote replication stress and genomic instability and have been implicated in several diseases. We report here the impact of the ribonucleotide rATP and of its naturally occurring damaged analog 1,N6-ethenoadenosine (1,N6-ϵrA) on translesion synthesis (TLS), mediated by human DNA polymerase η (hpol η), and on RNase H2–mediated incision. Mass spectral analysis revealed that 1,N6-ϵrA in DNA generates extensive frameshifts during TLS, which can lead to genomic instability. Moreover, steady-state kinetic analysis of the TLS process indicated that deoxypurines (i.e. dATP and dGTP) are inserted predominantly opposite 1,N6-ϵrA. We also show that hpol η acts as a reverse transcriptase in the presence of damaged ribonucleotide 1,N6-ϵrA but has poor RNA primer extension activities. Steady-state kinetic analysis of reverse transcription and RNA primer extension showed that hpol η favors the addition of dATP and dGTP opposite 1,N6-ϵrA. We also found that RNase H2 recognizes 1,N6-ϵrA but has limited incision activity across from this lesion, which can lead to the persistence of this detrimental DNA adduct. We conclude that the damaged and unrepaired ribonucleotide 1,N6-ϵrA in DNA exhibits mutagenic potential and can also alter the reading frame in an mRNA transcript because 1,N6-ϵrA is incompletely incised by RNase H2.

(Universitat Pompeu Fabra - Barcelona) Expansions by groups of humans were common during prehistoric times, after the adoption of agriculture. Among other factors, this is due to population growth of farmers which was greater than of that hunter-gatherers. We can find one example of this during the Neolithic period, when farming was introduced to Europe by migrations from the Middle East.

Up-and-coming recording artiste Kaay Jones says she did not know she was becoming part of a transformational music project that would connect her to a wide cross section of talent in the Caribbean. Jones carries Jamaica's flag in a unified...

The Ministry of Health and Wellness has reported ten new positive COVID-19 test results, pushing the tally of confirmed cases to 488. Among the ten new cases, eight are females, and two are males. Their ages range from four years to 39-years-...

Data from March shows similarities in spending across various demographics.

Rationale: Despite its widespread use in oncology, the PET radiotracer ¹⁸F-FDG is ineffective for improving early detection of pancreatic ductal adenocarcinoma (PDAC). An alternative strategy for early detection of pancreatic cancer involves visualisation of high-grade pancreatic intraepithelial neoplasias (PanIN-3), generally regarded as the non-invasive precursors of PDAC. The DNA damage response is known to be hyper-activated in late-stage PanINs. Therefore, we investigated whether the SPECT imaging agent, ¹¹¹In-anti-H2AX-TAT, allows visualisation of the DNA damage repair marker H2AX in PanIN-3s in an engineered mouse model of PDAC, to facilitate early detection of PDAC. Methods: Genetically engineered KPC mice (KRasLSL.G12D/+; p53LSL.R172H/+; PdxCre) were imaged with ¹⁸F-FDG and ¹¹¹In-anti-H2AX-TAT. PanIN/PDAC presence visualised by histology was compared with autoradiography and immunofluorescence. Separately, the survival of KPC mice imaged with ¹¹¹In-anti-H2AX-TAT was evaluated. Results: In KPC mouse pancreata, H2AX expression was increased in high-grade PanINs, but not in PDAC, corroborating earlier results obtained from human pancreas sections. Uptake of ¹¹¹In-anti-H2AX-TAT, but not ¹¹¹In-IgG-TAT or ¹⁸F-FDG, within the pancreas was positively correlated with the age of KPC mice, which was correlated with the number of high-grade PanINs. ¹¹¹In-anti-H2AX-TAT localises preferentially in high-grade PanIN lesions, but not in established PDAC. Younger, non-tumour-bearing KPC mice that show uptake of ¹¹¹In-anti-H2AX-TAT in the pancreas survive significantly shorter than mice with physiological ¹¹¹In-anti-H2AX-TAT uptake. Conclusion: ¹¹¹In-anti-H2AX-TAT imaging allows non-invasive detection of DNA damage repair signalling upregulation in pre-invasive PanIN lesions and is a promising new tool to aid in the early detection and staging of pancreatic cancer.

The prostate-specific membrane antigen (PSMA) is an excellent target for theranostic applications in prostate cancer (PCa). However, PSMA-targeted radioligand therapy can cause undesirable effects due to high accumulation of PSMA radiotracers in salivary glands and kidneys. This study assessed orally administered monosodium glutamate (MSG) as a potential means of reducing kidney and salivary gland radiation exposure using a PSMA targeting radiotracer. Methods: This prospective, double-blind, placebo-controlled study enrolled 10 biochemically recurrent PCa patients. Each subject served as his own control. [¹⁸F]DCFPyl PET/CT imaging sessions were performed 3 – 7 days apart, following oral administration of either 12.7 g of MSG or placebo. Data from the two sets of images were analyzed by placing regions of interest on lacrimal, parotid and submandibular glands, left ventricle, liver, spleen, kidneys, bowel, urinary bladder, gluteus muscle and malignant lesions. The results from MSG and placebo scans were compared by paired analysis of the ROI data. Results: A total of 142 pathological lesions along with normal tissues were analyzed. As hypothesized a priori, there was a significant decrease in maximal standardized uptake values corrected for lean body mass (SULmax) on images obtained following MSG administration in the parotids (24 ± 14%, P = 0.001), submandibular glands (35 ± 11%, P<0.001) and kidneys (23 ± 26%, P = 0.014). Significant decreases were also observed in lacrimal glands (49 ± 13%, P<0.001), liver (15 ± 6%, P<0.001), spleen (28 ± 13%, P = 0.001) and bowel (44 ± 13%, P<0.001). Mildly lower blood pool SULmean was observed after MSG administration (decrease of 11 ± 13%, P = 0.021). However, significantly lower radiotracer uptake in terms of SULmean, SULpeak, and SULmax was observed in malignant lesions on scans performed after MSG administration compared to the placebo studies (SULmax median decrease 33%, range -1 to 75%, P<0.001). No significant adverse events occurred and vital signs were stable following placebo or MSG administration. Conclusion: Orally administered MSG significantly decreased salivary gland, kidney and other normal organ PSMA radiotracer uptake in human subjects, using [¹⁸F]DCFPyL as an exemplar. However, MSG caused a corresponding reduction in tumor uptake, which may limit the benefits of this approach for diagnostic and therapeutic applications.

This week host Matt Egan kicks things off by chatting to staff writer Lewis Painter about the (genuinely) impressive Huawei P9 phone release. Then, acting editor at Macworld.co.uk David Price jumps in to discuss Whatsapp encryption (12:30) and the Panama Papers. Finally, Christina Mercer, online editor at Techworld.com, introduces you to the wonderful world of Li-Fi (24:30).  

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This week Ashleigh Allsopp is simultaneously fascinated and worried by the UK launch of Amazon's Dash buttons, and discusses the many wonderful and not-so-wonderful things they enable you to buy on a drunken whim. Then David Price takes his turn to shine a spotlight on Apple's mysterious tax affairs (12:20) and tries to explain why the Irish government doesn't want to be given 13 billion euros. Finally a surprisingly riled-up Neil Bennett explains why women wearing headphones are not fair game for dimwitted pick-up artists (25:00), and ponders the social conventions surrounding the place of technology in each of our lives.  

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This week Henry Burrell is in the presenter chair and he has brought puns, sing-songs and tenuous Field of Dreams references. First up is producer Chris to discuss the Fitbit acquisition of fellow wearable maker Pebble and why owners are sad. Then online editor at Techworld Tamlin Magee is discussing the Met Police's decision to upload their body camera footage to the cloud and why this could be problematic (12:00). Finally, fellow online editor Scott Carey runs us through the Amazon Go news and how the retail giant is trying to pull off the technology behind its 'just walk out' shopping experience (24:00).  

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Join host Henry Burrell in conversation with two editors, Karen Khan of Macworld UK in her debut pod along with pod regular Charlotte Jee of Techworld. We tackle the issues of privacy and self esteem, particularly in the young people that we are not, and ask who this product is for (because surely it will sell). Tech obviously plays a big part in the selfie phenomenon/epidemic. Second we discuss automation and how it is affecting the job market. Can a robot make an iPhone? Is Trump right about bringin' it all back home? What should politicians be doing to understand the technology involved? Thanks for listening, listener.  

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We return like a nerdy phoenix for episode 66, where Henry Burrell leads David Price and Dominic Preston down the tech rabbit hole to discuss the week's news. Amazon Prime Day came and went, but what does it really mean for consumers and the media? Did you buy anything? Did you need it? The team then discuss the odd ongoing story of the man who lost copyright of an image of a monkey to... the monkey that allegedly took it. PETA got involved. It's weird. It's good to be back.  

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We back. Google and Amazon introduced a raft of new products for us to drool over and, of course, apply a degree of scepticism. Jim Martin was on the ground to use all the new Google stuff and has the latest. Scott then talks us through Uber's mishaps, this time its London licence has been revoked. Will the company go public when it wants to? Finally we discuss the SNES Mini which we managed to get our hands on and why Nintendo has such low stock of all its great products.  

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This week host Charlotte Jee breaks down open banking with Computerworld UK editor Scott Carey: what is it and why should we care?

Then audience development editor Christina Mercer explains why chip-maker Qualcomm has been fined nearly €1 billion and the EU's sustained attack on big tech (12:00)

Last up is senior staff writer at Tech Advisor Dom Preston to talk about Amazon's revolutionary concept Go store opening in Seattle and if this is really the future of shopping (20:00).

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This week our host Scott Carey is joined by Macworld UK editor Karen Khan to chat about Apple's latest blockbuster results.

Then group production editor Tamlin Magee jumps in to discuss Amazon's working practices following the collective action around Prime Day.

Finally, Scott chats through his experience at the Google Cloud Next conference in San Francisco last week to see how it is trying to compete with the big boys at Amazon and Microsoft.

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The brain mechanisms underlying the association of hyperglycemia with depressive symptoms are unknown. We hypothesized that disrupted glutamate metabolism in pregenual anterior cingulate cortex (ACC) in type 1 diabetes (T1D) without depression affects emotional processing. Using proton magnetic resonance spectroscopy (MRS), we measured glutamate concentrations in ACC and occipital cortex (OCC) in 13 T1D without major depression (HbA1c=7.1±0.7% [54±7mmol/mol]) and 11 healthy non-diabetic controls (HbA1c=5.5±0.2% [37±3mmol/mol]) during fasting euglycemia (EU) followed by a 60-minute +5.5mmol/l hyperglycemic clamp (HG). Intrinsic neuronal activity was assessed using resting-state blood oxygen level dependent functional MRI to measure the fractional amplitude of low frequency fluctuations in slow-band 4 (fALFF4). Emotional processing and depressive symptoms were assessed using emotional tasks (Emotional-Stroop, Self-Referent-Encoding-Task SRET) and clinical ratings (HAM-D, SCL-90-R), respectively. During HG, ACC glutamate increased (1.2mmol/kg, +10%, p=0.014) while ACC fALFF4 was unchanged (-0.007, -2%, p=0.449) in T1D; in contrast, glutamate was unchanged (-0.2mmol/kg, -2%, p=0.578) while fALFF4 decreased (-0.05, -13%, p=0.002) in controls. OCC glutamate and fALFF4 were unchanged in both groups. T1D had longer SRET negative-word response-times (p=0.017) and higher depression-rating scores (HAM-D p=0.020; SCL-90-R-depression p=0.008). Higher glutamate change tended to associate with longer Emotional-Stroop response-times in T1D only. Brain glutamate must be tightly controlled during hyperglycemia due to the risk for neurotoxicity with excessive levels. Results suggest that ACC glutamate control mechanisms are disrupted in T1D, which affects glutamatergic neurotransmission related to emotional or cognitive processing. Increased prefrontal glutamate during acute hyperglycemic episodes could explain our previous findings of associations between chronic hyperglycemia, cortical thinning and depressive symptoms in T1D.

Tisu Super Tahan Lama merupakan tisu antiseptik sekaligus obat kuat oles tahan lama , efektif atasi ejakulasi dini pria dengan harga sangat ekonomis

Maximum Powerful Obat Kuat Pria adalah ramuan herbal alami yang berkhasiat sebagai obat kuat tahan lama,serta mengatasi ejakulasi dini, impotensi dan dll

Jamaica’s senior men’s ice hockey team’s historic championship win at last year’s Amerigol LATAM Cup is memorialised in a Canadian sports yearbook published earlier this year. The team copped the championship in its first international outing...

(CMC): The European Union (EU) will be making a second donation of medical supplies and equipment to Jamaica in support of the country’s efforts to tackle COVID-19, the Head of the EU Delegation to Jamaica, Ambassador Malgorzata Wasilewska,...

It does not matter that he does not listen to you, That you’d rather he say your neck Is as graceful as an antelopes, Perhaps he’s not accustomed to lying. If he bought you an expensive phone you, Dropped in the bath the next day, would You, In yellow, Say he does not love you? […]

1 June 2012 , Volume 68, Number 4

Eyes in the skies keeping watch on a planet under stress. Click on the PDF link to view the graphic

LOCAL MUSICIAN Janine JKUHL’s two-month-long immersive creative residency programme in Bali, Indonesia, has been extended indefinitely, or at least until the world has the COVID-19 spread under control and international airports open up to...

As Jamaica signs off on Budget 2020-2021, we are still uncertain whether we will be able to withstand the economic onslaught that will accompany the crisis in the years to come. It is clear that this pandemic is like none other that we have seen...

On Tuesday, April 14, the International Monetary Fund downgraded Jamaica’s growth prospects to -5.6 per cent. This is a severe contraction warranting substantial Government intervention. However, at times, the Government waits too late to respond...

The global COVID-19 spread has gone from bad to worse, with over 3.2 million confirmed cases and close to 250,000 deaths, not only has this pandemic claimed innumerable lives, it has also destabilised economies by freezing trade and other economic...

Empathetic, God-fearing, humanitarian, motivated, and optimistic – these are just a few words that come to mind when one thinks of Dr Kazi-Ann Kasimbie. Dr Kasimbie is the CEO and founder of Psychfactor Consulting Services, a psychological...

Western Bureau: A number of swimming officials in western Jamaica say that the region’s struggles with underdevelopment will continue even if the COVID-19 pandemic is brought under control. They say this is because they still lack proper pools to...

In February World Health Organization (WHO) declared the microcephaly epidemic in South America an international public health emergency. Today, the US Centers for Disease Control and Prevention, the CDC, has confirmed that it’s is Zika virus which is causing that microcephaly.  The outbreak was originally spotted in Recife, in Brazil, and it’s...

Welcome back to Talk Evidence - where Helen Macdonald and Carl Heneghan take you through what's happening in the world of Evidence. This month we'll be discussing tramadol being prescripted postoperatively, and a new EBM verdict says that should change(1.36). How much preventable harm does healthcare causes (11.20. A canadian project to help...

Latoya Rose used the last $3,000 she had to invest in 26 baby chicks and feed with the hope of turning a profit after they matured. Last Friday, as the Spaldings resident went to her coop to feed the chickens, they were all gone. “When I don’t see...

It was not the landing the Jamaicans who arrived at Kingston’s Norman Manley International Airport on Wednesday evening would want again. The 43 Jamaican ship workers of the Marella Discovery 2 were among the 115 people aboard the TUI charter flight that touched down amid the Kingston breeze and evening sunset.

“I know this has been some difficult times for us with the pandemic, but I know we are going to get through this together – Jamaica together. We are going to continue our social distancing. We are going to continue practising our incredible hygiene...

KINGSTOWN, St Vincent, CMC – St Vincent and the Grenadines students in Jamaica wanting to return home amid the coronavirus (COVID-19, including locked borders, must each pay an estimated US$1,3339 for a return flight. In a letter to the...