We search for energetic electron recoil signals induced by boosted dark matter (BDM) from the galactic center using the COSINE-100 array of NaI(Tl) crystal detectors at the Yangyang Underground ...Laboratory. The signal would be an excess of events with energies above 4 MeV over the well-understood background. Because no excess of events are observed in a 97.7 kg·yr exposure, we set limits on BDM interactions under a variety of hypotheses. Notably, we explored the dark photon parameter space, leading to competitive limits compared to direct dark photon search experiments, particularly for dark photon masses below 4 MeV and considering the invisible decay mode. Furthermore, by comparing our results with a previous BDM search conducted by the Super-Kamionkande experiment, we found that the COSINE-100 detector has advantages in searching for low-mass dark matter. This analysis demonstrates the potential of the COSINE-100 detector to search for MeV electron recoil signals produced by the dark sector particle interactions.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
A search for inelastic boosted dark matter (IBDM) using the COSINE-100 detector with 59.5 days of data is presented. This relativistic dark matter is theorized to interact with the target material ...through inelastic scattering with electrons, creating a heavier state that subsequently produces standard model particles, such as an electron-positron pair. In this study, we search for this electron-positron pair in coincidence with the initially scattered electron as a signature for an IBDM interaction. No excess over the predicted background event rate is observed. Therefore, we present limits on IBDM interactions under various hypotheses, one of which allows us to explore an area of the dark photon parameter space that has not yet been covered by other experiments. This is the first experimental search for IBDM using a terrestrial detector.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
Hippocampus-associated cognitive impairments are a common, highly conserved symptom of both schizophrenia (SCZ) and bipolar disorder (BPD). Although the hippocampus is likely an impacted region in ...SCZ/BPD patients, the molecular and cellular underpinnings of these impairments are difficult to identify. An emerging class of mouse models for these psychiatric diseases display similar cognitive impairments to those observed in human patients. The hippocampi of these mice possess a conserved pathophysiological alteration; we term the 'immature dentate gyrus' (iDG), characterized by increased numbers of calretinin-positive immature neuronal progenitors, a dearth of calbindin-positive mature neurons and (often) constitutively increased neurogenesis. Although these models provide a link between cellular dysfunction and behavioral alteration, limited translational validity exists linking the iDG to human pathophysiology. In this study, we report the initial identification of an iDG-like phenotype in the hippocampi of human SCZ/BPD patients. These findings suggest a new motif for the etiology of these diseases and link an emerging class of mouse models to the human disease condition.
The central regulator of adipogenesis, PPARγ, is a nuclear receptor that is linked to obesity and metabolic diseases. Here we report that MKRN1 is an E3 ligase of PPARγ that induces its ...ubiquitination, followed by proteasome-dependent degradation. Furthermore, we identified two lysine sites at 184 and 185 that appear to be targeted for ubiquitination by MKRN1. Stable overexpression of MKRN1 reduced PPARγ protein levels and suppressed adipocyte differentiation in 3T3-L1 and C3H10T1/2 cells. In contrast, MKRN1 depletion stimulated adipocyte differentiation in these cells. Finally, MKRN1 knockout MEFs showed an increased capacity for adipocyte differentiation compared with wild-type MEFs, with a concomitant increase of PPARγ and adipogenic markers. Together, these data indicate that MKRN1 is an elusive PPARγ E3 ligase that targets PPARγ for proteasomal degradation by ubiquitin-dependent pathways, and further depict MKRN1 as a novel target for diseases involving PPARγ.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The rapid diagnosis of tuberculosis (TB) is important for patient treatment and infection control. Current molecular diagnostic techniques for TB have insufficient sensitivity to detect samples with ...low bacterial loads. The sensitivity of molecular testing depends on not only the performance of the assay technique but also the nucleic acid extraction method. Here, we present a novel approach using exosomal DNA (exoDNA) and droplet digital PCR (ddPCR) platforms to detect Mycobacterium tuberculosis DNA in clinical samples.
The ddPCR platform targeting IS6110 was evaluated in parallel using total DNA and exoDNA. The clinical performance of ddPCR method was assessed with 190 respiratory samples from patients with suspected pulmonary TB.
Compared with mycobacterial culture, sensitivity and specificity of ddPCR were 61.5% (95% CI 44.6–76.6%) and 98.0% (95% CI 94.3–99.6%) using total DNA, and 76.9% (95% CI 60.7–88.9%) and 98.0% (95% CI 94.3–99.6%) using exoDNA, respectively. Among 15 culture-positive specimens with low concentrations of target molecules (2~99 positive droplets with exoDNA), only 53.3% (8/15), 46.7% (7/15), and 26.7% (4/15) of cases were detected using ddPCR with total DNA, real-time PCR with exoDNA, and real-time PCR with total DNA, respectively.
Our platform using ddPCR and exoDNA has the potential to provide sensitive and accurate methodology for TB diagnosis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Several studies have investigated the possibility of dairy foods and calcium (Ca) mediating weight and body composition, but a consensus has not been reached. We aimed to investigate ...weight-loss-related outcomes during intervention with low-fat dairy foods or Ca + vitamin D supplements, both as complements to hypocaloric diets. Overweight/obese Caucasian, early-postmenopausal women (
= 135) were recruited for a 6 month energy-restricted weight loss study complemented with either low-fat dairy foods (D; 4-5 servings/day), or Ca + vitamin D supplements (S); both to amount a total of ~1500 mg/day and 600 IU/day of Ca and vitamin D, respectively, or placebo pills (C). Bone mineral density (BMD) and lean and fat tissue were measured by Lunar iDXA. Serum and urinary markers of bone turnover were analyzed. Diet and physical activity were assessed with 3-day records. Participants on average lost ~4%, ~3%, and ~2% of body weight, fat, and lean tissue, respectively. The significantly better outcomes were noticed in participants in the D group regarding body composition (fat loss/lean tissue preservation) and in participants in the S group regarding the BMD outcomes, compared to those in the C group. Therefore, increasing low-fat dairy foods to 4-5 servings/day and/or increasing Ca & vitamin D intake by supplements (in those who are at the borderline dietary intake) may be beneficial for weight loss/maintenance and may lead to more favorable bone and body composition outcomes in postmenopausal women during moderate weight loss.
Memapsin 2 (β-secretase) is one of two proteases that cleave the β-amyloid precursor protein (APP) to produce the 40−42 residue amyloid-β peptide (Aβ) in the human brain, a key event in the ...progression of Alzheimer's disease. On the basis of the X-ray crystal structure of our lead inhibitor (2, OM99-2 with eight residues) bound to memapsin, we have reduced the molecular weight and designed potent memapsin inhibitors. Structure-based design and preliminary structure−activity studies have been presented.
Circadian rhythms of behavior are driven by oscillators in the brain that are coupled to the environmental light cycle. Circadian rhythms of gene expression occur widely in peripheral organs. It is ...unclear how these multiple rhythms are coupled together to form a coherent system. To study such coupling, we investigated the effects of cycles of food availability (which exert powerful entraining effects on behavior) on the rhythms of gene expression in the liver, lung, and suprachiasmatic nucleus (SCN). We used a transgenic rat model whose tissues express luciferase in vitro. Although rhythmicity in the SCN remained phase-locked to the light-dark cycle, restricted feeding rapidly entrained the liver, shifting its rhythm by 10 hours within 2 days. Our results demonstrate that feeding cycles can entrain the liver independently of the SCN and the light cycle, and they suggest the need to reexamine the mammalian circadian hierarchy. They also raise the possibility that peripheral circadian oscillators like those in the liver may be coupled to the SCN primarily through rhythmic behavior, such as feeding.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
The DESH (disproportionately enlarged subarachnoid-space hydrocephalus) pattern of "tight high-convexity and medial subarachnoid spaces, and enlarged Sylvian fissures with ventriculomegaly" is used ...to determine which patients undergo an operation for adult hydrocephalus at many centers. Our aim was to review adult hydrocephalus cases when DESH has not been a criterion for an operation to determine the prevalence of DESH among the cohort and compare the surgical outcomes in the presence or absence of DESH.
A retrospective cohort study was conducted at a single institution (Johns Hopkins Hospital) to include patients surgically treated for adult hydrocephalus between 2003 and 2014 drawn from a data base of patients who had undergone standardized hydrocephalus protocol MR imaging. Preoperative imaging was reviewed by 2 blinded neuroradiologists to characterize the presence of DESH. Preoperative and postoperative clinical symptomatology was recorded. Frequencies were compared using the Fisher exact test, and nonparametric means were compared using the Mann-Whitney
Test.
One hundred thirty-three subjects were identified and included (96 DESH absent, 37 DESH present). Shunting led to significant improvement in gait and urinary and cognitive symptoms for the overall cohort and for patients with and without DESH (
< .05). The Fisher exact test did not demonstrate any significant differences in either gait or urinary or cognitive symptom improvement between patients with or without DESH (
> .05).
The current study demonstrated symptom improvement in patients with adult hydrocephalus following shunting, with no significant differences between subjects with and without DESH. Thus, shunt insertion for patients with adult hydrocephalus should not rely solely on the presence of preoperative DESH findings.
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