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Two blinding corneal dystrophies, pediatric-onset congenital hereditary endothelial dystrophy (CHED) and some cases of late-onset Fuchs endothelial corneal dystrophy (FECD), are caused by SLC4A11 mutations. Three N-terminal SLC4A11 variants: v1, v2 and v3 are expressed in humans. We set out to determine which of these transcripts and what translated products, are present in corneal endothelium as these would be most relevant for CHED and FECD studies. Reverse transcription PCR (RT-PCR) and quantitative RT-PCR revealed only v2 and v3 mRNA in human cornea, but v2 was most abundant. Immunoblots probed with variant-specific antibodies revealed that v2 protein is about four times more abundant than v3 in human corneal endothelium. Bioinformatics and protein analysis using variant-specific antibodies revealed that second methionine in the open reading frame (M36) acts as translation initiation site on SLC4A11 v2 in human cornea. The v2 variants starting at M1 (v2-M1) and M36 (v2-M36) were indistinguishable in their cell surface trafficking and transport function (water flux). Structural homology models of v2-M36 and v3 suggest structural differences but their significance remains unclear. A combination of bioinformatics, RNA quantification and isoform-specific antibodies allows us to conclude that SLC4A11 variant 2 with start site M36 is predominant in corneal endothelium.

Sepsis and septic shock are the leading causes of death in critically ill patients. Acute intestinal ischemia/reperfusion (AII/R) is an adaptive response to shock. The high mortality rate from AII/R is due to the severity of the disease and, more importantly, the failure of timely diagnosis. The objective of this investigation is to use nuclear magnetic resonance (NMR) analysis to characterize urine metabolomic profile of AII/R injury in a mouse model. Animals were exposed to sham, early (30 min) or late (60 min) acute intestinal ischemia by complete occlusion of the superior mesenteric artery, followed by 2 hrs of reperfusion. Urine was collected and analyzed by NMR spectroscopy. Urinary metabolite concentrations demonstrated that different profiles could be delineated based on the duration of the intestinal ischemia. Metabolites such as allantoin, creatinine, proline, and methylamine could be predictive of AII/R injury. Lactate, currently used for clinical diagnosis, was found not to significantly contribute to the classification model for either early or late ischemia. This study demonstrates that patterns of changes in urinary metabolites are effective at distinguishing AII/R progression in an animal model. This is a proof-of-concept study to further support examination of metabolites in the clinical diagnosis of intestinal ischemia reperfusion injury in patients. The discovery of a fingerprint metabolite profile of AII/R will be a major advancement in the diagnosis, treatment, and prevention of systemic injury in critically ill patients.

ObjectiveHuman milk composition is dynamic. While extensive research has focused on its macronutrient concentrations during the first 6 months of lactation, limited research exists for extended lactation periods. This study aims to examine the nutritional composition of human milk during these longer lactation phases.DesignA retrospective longitudinal cohort study performed within the National Dutch Human Milk Bank.ParticipantsWe selected donors who had provided milk donations at least once after the 6-month postpartum mark.Main outcome measuresThe Miris Human Milk Analyser was used to analyse macronutrient concentrations in the milk samples. Linear mixed models were used for longitudinal analysis of these concentrations, factoring in time variables established for six sequential lactation periods.ResultsWe analysed 820 milk samples from 86 women, collected between 5 weeks and 28 months postpartum. Initially, milk protein concentrations dropped over the first 8 months of lactation (diff = −0.19 g/dL, p<0.001) and stabilised between 8 and 18 months before increasing again by 0.21 (95% CI 0.06–0.21) g/dL. Carbohydrate concentrations remained steady throughout the study period. Fat concentrations were stable for the first 8 months but saw an increase afterwards. Post 18 months, the fat content saw a rise of 1.90 (95% CI 1.59–2.21) g/dL. The caloric density mirrored the pattern of the fat concentrations.ConclusionThe nutritional content of human milk does not decrease after 6 months of lactation. Therefore, human milk banks may accept donations from mothers up to 2 years post-birth.

Nitrogen-vacancy (NV) centers have considerable promise as high sensitivity magnetometers, however are commonly limited by inefficient collection and low contrasts. Laser threshold magnetometry (LTM) enables efficient collection and high contrasts, providing a path towards higher sensitivity magnetometry. We demonstrate an infrared LTM using an ensemble of NV centers in a single crystal diamond plate integrated into a vertical external cavity surface emitting laser. The laser was tuned to the spin dependent absorption line of the NV centers, allowing for optical readout by monitoring the laser output power. We demonstrate a magnetic sensitivity of 7.5~nT/\\(\\sqrt{\\textit{Hz}}\\) in the frequency range between 10 and 50 Hz. Furthermore, the contrast and the projected PSNL sensitivity are shown to improve significantly by operating close to the lasing threshold, achieving 18.4\\% and 26.6~pT/\\(\\sqrt{\\textit{Hz}}\\) near threshold. What's more, an unexpected saturable absorption phenomenon was observed near threshold, which enhanced the contrast and projected PSNL sensitivity.

[Jay-Z] showed last night that he fully deserves his extraordinary rise from humble beginnings as a Brooklyn crack dealer to all-time-great status as a rapper, as well as becoming half of hip-hop's premier power couple alongside Beyonce who drove the crowd berserk when she joined her man on stage. Always a favourite with UK audiences, Jay-Z's hip-hop version of Beware Of The Boys, the classic British Asian bhangra track, created a storm, provoking a particularly strong response with the line \"Leave Iraq alone!\" Confusion briefly took over as the DJ threw on the unmistakable beat of Made You Look, a track by fellow New York rapper, Nas. This turn of events was especially puzzling, since Jay- Z and Nas have engaged in bitter verbal warfare over the past few years. Those of us who were aware that Jay-Z, who is CEO of Def Jam Recordings, signed Nas to the label earlier this year, were slightly less surprised by this rapprochement, but watching these all-time greats share the stage was a thrilling experience nonetheless.

Heaven, a sizzling duet with Stephanie McKay, captures the engaging passion and tenderness of Marvin Gaye's songs with Diana Ross. And the old-school synths and soaring vocals of You Could Be Mine are reminiscent of Stevie Wonder. Despite these delights and the impressive variety displayed by If I Don't - an upbeat jazzy corker laced with a cheeky minor-key clarinet - these self-penned tracks fail to deliver the promised brilliance. He should follow Gaye's example and enlist some songwriters.