CITATIONSleep is a biological necessity, and insufficient sleep and untreated sleep disorders are detrimental for health, well-being, and public safety. Healthy People 2030 includes several ...sleep-related objectives with the goal to improve health, productivity, well-being, quality of life, and safety by helping people get enough sleep. In addition to adequate sleep duration, healthy sleep requires good quality, appropriate timing, regularity, and the absence of sleep disorders. It is the position of the American Academy of Sleep Medicine (AASM) that sleep is essential to health. There is a significant need for greater emphasis on sleep health in education, clinical practice, inpatient and long-term care, public health promotion, and the workplace. More sleep and circadian research is needed to further elucidate the importance of sleep for public health and the contributions of insufficient sleep to health disparities. CITATIONRamar K, Malhotra RK, Carden KA, et al. Sleep is essential to health: an American Academy of Sleep Medicine position statement. J Clin Sleep Med. 2021;17(10):2115-2119.
Obstructive Sleep Apnea, Obesity, and the Risk of Incident Atrial Fibrillation Apoor S. Gami, Dave O. Hodge, Regina M. Herges, Eric J. Olson, Jiri Nykodym, Tomas Kara, Virend K. Somers Obesity is a ...risk factor for atrial fibrillation/flutter (AF), and obstructive sleep apnea (OSA) is associated with both obesity and AF. It is unknown whether OSA predicts new-onset AF independently of obesity. We assessed the incidence of AF during an average of 4.7 years follow-up in a cohort of 3,542 Olmsted County adults without a history of AF who underwent polysomnography from 1987 to 2003. In subjects <65 years of age, independent predictors of incident AF were age, male gender, coronary artery disease, body mass index, and the decrease in nocturnal oxygen saturation, which is an important pathophysiological consequence of OSA.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Induction of histone acetylation in the nucleus accumbens (NAc), a key brain reward region, promotes cocaine-induced alterations in gene expression. Histone deacetylases (HDACs) tightly regulate the ...acetylation of histone tails, but little is known about the functional specificity of different HDAC isoforms in the development and maintenance of cocaine-induced plasticity, and previous studies of HDAC inhibitors report conflicting effects on cocaine-elicited behavioral adaptations. Here we demonstrate that specific and prolonged blockade of HDAC1 in NAc of mice increased global levels of histone acetylation, but also induced repressive histone methylation and antagonized cocaine-induced changes in behavior, an effect mediated in part through a chromatin-mediated suppression of GABAA receptor subunit expression and inhibitory tone on NAc neurons. Our findings suggest a new mechanism by which prolonged and selective HDAC inhibition can alter behavioral and molecular adaptations to cocaine and inform the development of therapeutics for cocaine addiction.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Previous work has identified alterations in histone acetylation in animal models of drug addiction and depression. However, the mechanisms which integrate drugs and stress with changes in chromatin ...structure remain unclear. Here, we identify the activity-dependent class II histone deacetylase, HDAC5, as a central integrator of these stimuli with changes in chromatin structure and gene expression. Chronic, but not acute, exposure to cocaine or stress decreases HDAC5 function in the nucleus accumbens (NAc), a major brain reward region, which allows for increased histone acetylation and transcription of HDAC5 target genes. This regulation is behaviorally important, as loss of HDAC5 causes hypersensitive responses to chronic, not acute, cocaine or stress. These findings suggest that proper balance of histone acetylation is a crucial factor in the saliency of a given stimulus and that disruption of this balance is involved in the transition from an acute adaptive response to a chronic psychiatric illness.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The method of continuous variation (often referred to as Job’s method) is an easy and common method for the determination of the reactant stoichiometry of chemical equilibria. The traditional ...interpretation of Job plots has been limited to complex association equilibria of the type nA + mB ⇌ A n B m , while little focus has been placed upon displacement type reactions (e.g., A + B ⇌ C + D), which can give Job plots that look quite similar. We developed a novel method that allows the user to accurately distinguish between 1:1 complex association, 2:2 complex association, and displacement reactions using nothing more than a pocket calculator. This method involves preparing a Job plot of the system under investigation (using regularly spaced mole fractions), normalizing the measured quantities (such as the concentration of A n B m or C for the above reactions) to their maximum value (i.e., at mole fraction 0.5), and determining the sum of the normalized values. This sum is then compared with theoretically predicted normalized sum values that depend on the nature of the equilibrium. The relationship between, on the one hand, the sum of the normalized values and, on the other hand, the reaction equilibrium constant and the concentration of the stock solutions used for the preparation of the Job plot is also explored. The use of this new technique for the interpretation of Job plots permits users to readily determine information that can be obtained otherwise only with laborious additional experiments, as illustrated by the analysis of four Job plots taken from the literature.
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IJS, KILJ, NUK, PNG, UL, UM
Hypervirulent (hypermucoviscous) Klebsiella pneumoniae (hvKP) strains are an emerging variant of "classical" K. pneumoniae (cKP) that cause organ and life-threatening infection in healthy ...individuals. An understanding of hvKP-specific virulence mechanisms that enabled evolution from cKP is limited. Observations by our group and previously published molecular epidemiologic data led us to hypothesize that hvKP strains produced more siderophores than cKP strains and that this trait enhanced hvKP virulence. Quantitative analysis of 12 hvKP strains in iron-poor minimal medium or human ascites fluid showed a significant and distinguishing 6- to 10-fold increase in siderophore production compared to that for 14 cKP strains. Surprisingly, high-pressure liquid chromatography (HPLC)-mass spectrometry and characterization of the hvKP strains hvKP1, A1142, and A1365 and their isogenic aerobactin-deficient (ΔiucA) derivatives established that aerobactin accounted for the overwhelming majority of increased siderophore production and that this was not due to gene copy number. Further, aerobactin was the primary factor in conditioned medium that enhanced the growth/survival of hvKP1 in human ascites fluid. Importantly the ex vivo growth/survival of hvKP1 ΔiucA was significantly less than that of hvKP1 in human ascites fluid, and the survival of outbred CD1 mice challenged subcutaneously or intraperitoneally with hvKP1 was significantly less than that of mice challenged with hvKP1 ΔiucA. The lowest subcutaneous and intraperitoneal challenge inocula of 3 × 10(2) and 3.2 × 10(1) CFU, respectively, resulted in 100% mortality, demonstrating the virulence of hvKP1 and its ability to cause infection at a low dose. These data strongly support that aerobactin accounts for increased siderophore production in hvKP compared to cKP (a potential defining trait) and is an important virulence factor.
Background Hyperoxaluria and increased calcium oxalate stone formation occur after Roux-en-Y gastric bypass (RYGB) surgery for morbid obesity. The etiology of this hyperoxaluria is unknown. We ...hypothesized that after bariatric surgery, intestinal hyperabsorption of oxalate contributes to increases in plasma oxalate and urinary calcium oxalate supersaturation. Methods We prospectively examined oxalate metabolism in 11 morbidly obese subjects before and 6 and 12 months after RYGB ( n = 9) and biliopancreatic diversion-duodenal switch (BPD-DS) ( n = 2). We measured 24-hour urinary supersaturations for calcium oxalate, apatite, brushite, uric acid, and sodium urate; fasting plasma oxalate; 72-hour fecal fat; and increases in urine oxalate following an oral oxalate load. Results Six and 12 months after RYGB, plasma oxalate and urine calcium oxalate supersaturation increased significantly compared with similar measurements obtained before surgery (all P ≤ .02). Fecal fat excretion at 6 and 12 months was increased ( P = .026 and .055, 0 vs 6 and 12 months). An increase in urine oxalate excretion after an oral dose of oxalate was observed at 6 and 12 months (all P ≤ .02). Therefore, after bariatric surgery, increases in fecal fat excretion, urinary oxalate excretion after an oral oxalate load, plasma oxalate, and urinary calcium oxalate supersaturation values were observed. Conclusion Enteric hyperoxaluria is often present in patients after the operations of RYGB and BPD-DS that utilize an element of intestinal malabsorption as a mechanism for weight loss.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Consumer sleep technologies (CSTs) are widespread applications and devices that purport to measure and even improve sleep. Sleep clinicians may frequently encounter CST in practice and, despite lack ...of validation against gold standard polysomnography, familiarity with these devices has become a patient expectation. This American Academy of Sleep Medicine position statement details the disadvantages and potential benefits of CSTs and provides guidance when approaching patient-generated health data from CSTs in a clinical setting. Given the lack of validation and United States Food and Drug Administration (FDA) clearance, CSTs cannot be utilized for the diagnosis and/or treatment of sleep disorders at this time. However, CSTs may be utilized to enhance the patient-clinician interaction when presented in the context of an appropriate clinical evaluation. The ubiquitous nature of CSTs may further sleep research and practice. However, future validation, access to raw data and algorithms, and FDA oversight are needed.
In optogenetics, researchers use light and genetically encoded photoreceptors to control biological processes with unmatched precision. However, outside of neuroscience, the impact of optogenetics ...has been limited by a lack of user-friendly, flexible, accessible hardware. Here, we engineer the Light Plate Apparatus (LPA), a device that can deliver two independent 310 to 1550 nm light signals to each well of a 24-well plate with intensity control over three orders of magnitude and millisecond resolution. Signals are programmed using an intuitive web tool named Iris. All components can be purchased for under $400 and the device can be assembled and calibrated by a non-expert in one day. We use the LPA to precisely control gene expression from blue, green, and red light responsive optogenetic tools in bacteria, yeast, and mammalian cells and simplify the entrainment of cyanobacterial circadian rhythm. The LPA dramatically reduces the entry barrier to optogenetics and photobiology experiments.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Two of the most-studied ecogeographical rules describe patterns of body size variation within species. Bergmann's rule predicts that individuals have larger body sizes in colder climates (typically ...at higher latitudes), and the island rule predicts that island populations of small-bodied species average larger in size than their mainland counterparts (insular gigantism). These rules are rarely tested in conjunction or assessed across space and time simultaneously. We investigated these patterns in the Northern Treeshrew (Tupaia belangeri) using museum specimens collected across a wide spatial and temporal range. Contrary to Bergmann's rule, size increases with temperature in T. belangeri, a signal that is highly consistent across space and time. We also show that these rules are intertwined: Bergmann's rule is reversed on the mainland but holds on islands, and therefore the island rule is upheld at higher, but not lower, latitudes. Moreover, we demonstrate a rapid reversal of both rules over time. The mechanism behind these inversions remains unclear, though temperature and precipitation are significant predictors of body size. Ecogeographical rules rely on the assumption of a constant relationship between size and the factors driving its variation. Our results highlight the need to question this assumption and reevaluate these rules in the context of accelerating and uneven climate change.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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