NADPH facilitates glucose-stimulated insulin secretion (GSIS) in pancreatic islet (PI) β-cells by an as yet unknown mechanism. We found NADPH oxidase, isoform-4 (NOX4), to be the major producer of cytosolic H₂O₂, essential for GSIS, while the increase in ATP/ADP alone was insufficient. The fast GSIS phase was absent in PIs from NOX4-null, β-cell-specific knockout mice (NOX4βKO) (not NOX2KO), and NOX4-silenced or catalase-overexpressing INS-1E cells. Lentiviral NOX4 overexpression or H₂O₂ rescued GSIS in PIs from NOX4βKO mice. NOX4 silencing suppressed Ca²⁺ oscillations and the patch-clamped ATP-sensitive potassium channel (K_ATP) opened more frequently at high glucose. Mitochondrial H₂O₂, decreasing upon GSIS, provided an alternative redox signaling when 2-oxo-isocaproate or fatty acid oxidation formed superoxide by electron-transport flavoprotein:Q-oxidoreductase. Unlike GSIS, this ceased with mitochondrial antioxidant SkQ1. Both NOX4KO and NOX4βKO strains exhibited impaired glucose tolerance and peripheral insulin resistance. Thus the redox signaling previously suggested to cause β-cell-self-checking – hypothetically induces insulin resistance when absent. In conclusion, ATP plus H₂O₂ elevations constitute an essential switch-on signal of insulin exocytosis for glucose and branched-chain oxoacids as secretagogues (partly for fatty acids). Redox signaling could be impaired by cytosolic antioxidants, hence those targeting mitochondria should be preferred for clinical applications to treat (pre)diabetes at any stage.

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

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...

Joachim Spranger
Mar 1, 2003; 52:812-817
Pathophysiology

Clinical studies have suggested that changes in peripheral nerve microcirculation may contribute to nerve damage in diabetic polyneuropathy (DN). High-sensitivity troponin T (hsTNT) assays have been recently shown to provide predictive values for both cardiac and peripheral microangiopathy in type 2 diabetes (T2D). This study investigated the association of sciatic nerve structural damage in 3 Tesla (3T) magnetic resonance neurography (MRN) with hsTNT and N-terminal pro-brain natriuretic peptide serum levels in patients with T2D. MRN at 3T was performed in 51 patients with T2D (23 without DN, 28 with DN) and 10 control subjects without diabetes. The sciatic nerve’s fractional anisotropy (FA), a marker of structural nerve integrity, was correlated with clinical, electrophysiological, and serological data. In patients with T2D, hsTNT showed a negative correlation with the sciatic nerve’s FA (r = –0.52, P < 0.001), with a closer correlation in DN patients (r = –0.66, P < 0.001). hsTNT further correlated positively with the neuropathy disability score (r = 0.39, P = 0.005). Negative correlations were found with sural nerve conduction velocities (NCVs) (r = –0.65, P < 0.001) and tibial NCVs (r = –0.44, P = 0.002) and amplitudes (r = –0.53, P < 0.001). This study is the first to show that hsTNT is a potential indicator for structural nerve damage in T2D. Our results indirectly support the hypothesis that microangiopathy contributes to structural nerve damage in T2D.

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.

George A. Bray
Apr 1, 2014; 37:950-956
Current Concepts of Type 2 Diabetes Prevention

George A. Bray
Apr 1, 2014; 37:950-956
Current Concepts of Type 2 Diabetes Prevention

OBJECTIVE

Acrylamide exposure from daily-consumed food has raised global concern. We aimed to assess the exposure-response relationships of internal acrylamide exposure with oxidative DNA damage, lipid peroxidation, and fasting plasma glucose (FPG) alteration and investigate the mediating role of oxidative DNA damage and lipid peroxidation in the association of internal acrylamide exposure with FPG.

This is what I think of as an honest cake - not tizzy, just homely, buttery and ever-so more-ish with its tender, nutty crumb and sweet, caramelised pineapple topping. I particularly love the way the sides, through some kind of magical alchemy of heat and sugar, become ever-so-slightly crunchy. There are a couple of little things I've noticed when I bake it - the first is that it cooks better and looks better when baked in a regular, not a non-stick, cake tin. And the second is that it's really important not to overload the tin with pineapple or it will release too much liquid and the centre of the cake will be soggy.

140g unsalted butter 200g dark chocolate 100g light brown sugar 100g caster sugar 2 teaspoons vanilla extract 2 eggs 1 egg yolk 85g plain flour 55g macadamia nuts, lightly toasted, chopped 30g crystallised ginger, chopped Sifted cocoa powder, to dust

I seriously love cooking on the Weber more in winter cooler temperature make us feel more cosy and accentuate the taste buds and smell . Replaced the traditional peanuts with our wonderful local macadamias

Delicious Australian dish with fresh Lilly Pilly and finger lime spritzer.

125g butter, softened 1 cup caster sugar 1 egg 1 tsp vanilla essence 1 and 1/2 cups plain flour, sifted 1 tsp baking powder 1/4 tsp. pepper leaf spice, ground 1 cup white chocolate chips 1/3 cup raw macadamia nuts, chopped

Love this time of year where our makers are abundant with the sweet aroma of fresh basil . Here is my take on a fancy potato salad of macadamia pesto , crispy prosciutto, sweet cherry tomatoes

The local lady finger bananas are so sweet and moorish!

This salad is inspired by a good chef friend of mine who cooked with me last weekend. Such a healthy way to enjoy broccoli which is so delicious at the moment. It's wonderful to utilize the whole vegetable and the added fibre in the stalk which we use in the salad.Feel free to explore with certain quantities in this recipe therefore I encourage you to taste and adjust to your own personal taste. You can also add chopped green olives which add an extra dimension.

Nothing beats beautifully roasted vegetables caramelized in their own sugar content to accompany a simple roast dinner or even on their own with a nice salad. The addition of perfumed lemon thyme and macadamia gives a nice touch.

This salad is our go-to staple. Everyone loves it. It's healthy, colourful and so, so easy. It can also be made entirely with local ingredients.

Exotic, different, really cool flavours, pared-back dessert and it's not too sweet. Enjoy!

OBJECTIVE

Plasma protein N-glycan profiling integrates information on enzymatic protein glycosylation, which is a highly controlled ubiquitous posttranslational modification. Here we investigate the ability of the plasma N-glycome to predict incidence of type 2 diabetes and cardiovascular diseases (CVDs; i.e., myocardial infarction and stroke).

As the threat of COVID-19 continues, infectious disease expert and TED Fellow Adam Kucharski answers five key questions about the novel coronavirus, providing necessary perspective on its transmission, how governments have responded and what might need to change about our social behavior to end the pandemic. (This video is excerpted from a 70-minute interview between Kucharski and head of TED Chris Anderson. Listen to the full interview at http://go.ted.com/adamkucharski. Recorded March 11, 2020)

By Emily Reynolds. Participants whose self-esteem was based on financial success felt more lonely and disconnected from others.

Told from two points of view: Drake: Most guys like their dads. Most guys aren't the son of the literal devil. When Daddy Dearest tells me its unseemly for the last living son of the Lord of Hell to be unmarried, I hate to think who he has in mind. Until, I remember I'm technically already married. Yeah, she's human and I was all of eight at the time. But, still counts. Now I just need to get my wife to Hell for a meet and greet with Pops and send her back home. Except, our marriage won't technically be legit until it's consummated. And I don't know that I want to send her home... Wren: Most girls live normal lives. Most girls aren't married to the devil's son. There is something weirdly familiar about the new guy next door, but I can't place it. Then a weird little demon thing turns up in my room to tell me a prince of Hell wishes for an audience with me. Oh, yeah. And, apparently - while I'm not even eighteen yet - he's my husband? So, I find myself stuck in Hell with a husband. And, I guess I don't hate it as much as I thought I would. There's always something going on and things to discover. And soon, I don't know that I want to go home.

Beastie Boys (Musical group)

War crime trials -- Australia.

Wild plants, Edible.

Menarche.

Lyricists -- Australia -- Biography.

Minter, Adam, 1970- -- Travel.

Wien : Urban & Schwarzenberg, 1893-1895.

Hannover : Köllner, 1898.

London : H.K. Lewis, 1890.

Edinburgi : Apud Balfour et Smellie, 1783.

Paris : G. Steinheil, 1895.

Stuttgart : F. Enke, 1895.

Detroit, Mich. : G.S. Davis, 1891.

London : W. Swan Sonnenschein, 1884-1885.

London : Swan Sonnenschein, 1897.

Goettingae : Litteris Ioann. Christ. Dieterich, Acad. Typogr, [1781]

Amstelodami : Typis A. Wolfgang, 1674.

London : Printed & sold by Thos. & John Bowles, printsellers, [1728]

Rockville, Maryland : National Institute on Drug Abuse, 1985.

Just two years removed from the euphoria of winning her second national championship, Muffet McGraw knew it was time. The Hall of Fame coach retired Wednesday with a resume that includes two national championships in 33 seasons at the school, a surprising decision to many of the countless players and coaches she has influenced on and off the court as a mentor and advocate for women. ''I am proud of what we have accomplished and I can turn the page to the next chapter in my life with no regrets, knowing that I gave it my best every day,'' said McGraw, a four-time winner of the AP women's basketball Coach of the Year.