Miracle-dz/UniFAR-FTUs huggingface dataset:
Coordination of Meristem Doming and the Floral Transition by Late Termination, a Kelch Repeat Protein

A kelch-containing repressor complex limits expression of the floral antagonist and meristem size promoter SELF PRUNING, thus restricting doming of the shoot apical meristem to the floral transition. Enlargement and doming of the shoot apical meristem (SAM) is a hallmark of the transition from vegetative growth to flowering. While this change is widespread, its role in the flowering process is unknown. The late termination (ltm) tomato (Solanum lycopersicum) mutant shows severely delayed flowering and precocious doming of the vegetative SAM. LTM encodes a kelch domain-containing protein, with no link to known meristem maintenance or flowering time pathways. LTM interacts with the TOPLESS corepressor and with several transcription factors that can provide specificity for its functions. A subgroup of flowering-associated genes is precociously upregulated in vegetative stages of ltm SAMs, among them, the antiflorigen gene SELF PRUNING (SP). A mutation in SP restored the structure of vegetative SAMs in ltm sp double mutants, and late flowering was partially suppressed, suggesting that LTM functions to suppress SP in the vegetative SAM. In agreement, SP-overexpressing wild-type plants exhibited precocious doming of vegetative SAMs combined with late flowering, as found in ltm plants. Strong flowering signals can result in termination of the SAM, usually by its differentiation into a flower. We propose that activation of a floral antagonist that promotes SAM growth in concert with floral transition protects it from such terminating effects.
The Human Leukocyte Antigen (HLA)-B27 Peptidome in Vivo, in Spondyloarthritis-susceptible HLA-B27 Transgenic Rats and the Effect of Erap1 Deletion *

HLA-B27 is a class I major histocompatibility (MHC-I) allele that confers susceptibility to the rheumatic disease ankylosing spondylitis (AS) by an unknown mechanism. ERAP1 is an aminopeptidase that trims peptides in the endoplasmic reticulum for binding to MHC-I molecules. ERAP1 shows genetic epistasis with HLA-B27 in conferring susceptibility to AS. Male HLA-B27 transgenic rats develop arthritis and serve as an animal model of AS, whereas female B27 transgenic rats remain healthy. We used large scale quantitative mass spectrometry to identify over 15,000 unique HLA-B27 peptide ligands, isolated after immunoaffinity purification of the B27 molecules from the spleens of HLA-B27 transgenic rats. Heterozygous deletion of Erap1, which reduced the Erap1 level to less than half, had no qualitative or quantitative effects on the B27 peptidome. Homozygous deletion of Erap1 affected approximately one-third of the B27 peptidome but left most of the B27 peptidome unchanged, suggesting the possibility that some of the HLA-B27 immunopeptidome is not processed in the presence of Erap1. Deletion of Erap1 was permissive for the AS-like phenotype, increased mean peptide length and increased the frequency of C-terminal hydrophobic residues and of N-terminal Ala, Ser, or Lys. The presence of Erap1 increased the frequency of C-terminal Lys and Arg, of Glu and Asp at intermediate residues, and of N-terminal Gly. Several peptides of potential interest in AS pathogenesis, previously identified in human cell lines, were isolated. However, rats susceptible to arthritis had B27 peptidomes similar to those of non-susceptible rats, and no peptides were found to be uniquely associated with arthritis. Whether specific B27-bound peptides are required for AS pathogenesis remains to be determined. Data are available via ProteomeXchange with identifier PXD005502.
The Arabidopsis Mitochondrial Protease FtSH4 Is Involved in Leaf Senescence via Regulation of WRKY-Dependent Salicylic Acid Accumulation and Signaling1

The mitochondria-localized protein FtSH4 regulates leaf senescence and modulates the cross talk of ROS, SA, and WRKY signaling pathways. Mitochondria and autophagy play important roles in the networks that regulate plant leaf senescence and cell death. However, the molecular mechanisms underlying the interactions between mitochondrial signaling and autophagy are currently not well understood. This study characterized the function of the Arabidopsis (Arabidopsis thaliana) mitochondrial AAA-protease gene FtSH4 in regulating autophagy and senescence, finding that FtSH4 mediates WRKY-dependent salicylic acid (SA) accumulation and signaling. Knockout of FtSH4 in the ftsh4-4 mutant resulted in severe leaf senescence, cell death, and high autophagy levels. The level of SA increased dramatically in the ftsh4-4 mutant. Expression of nahG in the ftsh4-4 mutant led to decreased SA levels and suppressed the leaf senescence and cell death phenotypes. The transcript levels of several SA synthesis and signaling genes, including SALICYLIC ACID INDUCTION DEFICIENT2 (SID2), NON-RACE-SPECIFIC DISEASE RESISTANCE1 (NDR1), and NONEXPRESSOR OF PATHOGENESIS-RELATED PROTEINS1 (NPR1), increased significantly in the ftsh4-4 mutants compared with the wild type. Loss of function of SID2, NDR1, or NPR1 in the ftsh4-4 mutant reversed the ftsh4-4 senescence and autophagy phenotypes. Furthermore, ftsh4-4 mutants had elevated levels of transcripts of several WRKY genes, including WRKY40, WRKY46, WRKY51, WRKY60, WRKY63, and WRKY75; all of these WRKY proteins can bind to the promoter of SID2. Loss of function of WRKY75 in the ftsh4-4 mutants decreased the levels of SA and reversed the senescence phenotype. Taken together, these results suggest that the mitochondrial ATP-dependent protease FtSH4 may regulate the expression of WRKY genes by modifying the level of reactive oxygen species and the WRKY transcription factors that control SA synthesis and signaling in autophagy and senescence.
Transplant size mismatch in restrictive lung disease

To maximize the benefit of lung transplantation, the effect of size mismatch on survival in lung transplant recipients with restrictive lung disease (RLD) was examined. All single and bilateral RLD lung transplants from 1987 to 2011 in the United Network for Organ Sharing (UNOS) Database were identified. Donor predicted total lung capacity (pTLC):Recipient pTLC ratio (pTLCr) quantified mismatch. pTLCr was segregated into five strata. A Cox proportional hazards model evaluated the association of pTLCr with mortality hazard. To identify a critical pTLCr, a Cox model using a restricted cubic spline for pTLCr was used. A total of 6656 transplants for RLD were identified. Median pTLCr for single orthotopic lung transplant (SOLT) and bilateral orthotopic lung transplant (BOLT) was 1.0 (0.69–1.47) and 0.98 (0.66–1.45). Examination of pTLCr as a categorical variable revealed that undersizing (pTLCr <0.8) for SOLT and moderate oversizing (pTLCr = 1.1–1.2) for SOLT and BOLT had a harmful survival effect [for SOLT pTLC <0.8: HR 1.711 (95% CI 1.146–2.557), P = 0.01 and for BOLT pTLC 1.1–1.2: HR 1.717 (95% CI 1.112–2.651), P = 0.02]. Spline analysis revealed significant changes in SOLT mortality by variation of pTLCr between 0.8–0.9 and 1.1–1.2. RLD patients undergoing SOLT are susceptible to detriments of an undersized lung. RLD patients undergoing BOLT have higher risk of mortality when pTLCr falls between 1.1 and 1.2.
Looking Inward and Back: Real-Time Monitoring of Visual Working Memories

Confidence in our memories is influenced by many factors, including beliefs about the perceptibility or memorability of certain kinds of objects and events, as well as knowledge about our skill sets, habits, and experiences. Notoriously, our knowledge and beliefs about memory can lead us astray, causing us to be overly confident in eyewitness testimony or to overestimate the frequency of recent experiences. Here, using visual working memory as a case study, we stripped away all these potentially misleading cues, requiring observers to make confidence judgments by directly assessing the quality of their memory representations. We show that individuals can monitor the status of information in working memory as it degrades over time. Our findings suggest that people have access to information reflecting the existence and quality of their working memories, and furthermore, that they can use this information to guide their behavior.
Cannabis in epilepsy: From clinical practice to basic research focusing on the possible role of cannabidivarin

Cannabidivarin (CBDV) and cannabidiol (CBD) have recently emerged among cannabinoids for their potential antiepileptic properties, as shown in several animal models. We report the case of a patient affected by symptomatic partial epilepsy who used cannabis as self‐medication after the failure of countless pharmacological/surgical treatments. Clinical and video electroencephalogram (EEG) evaluations were periodically performed, and the serum levels of CBDV, CBD, and Δ9‐tetrahydrocannabinol were repeatedly measured. After cannabis administration, a dramatic clinical improvement, in terms of both decrease in seizure frequency and recovery of cognitive functions, was observed, which might parallel high CBDV plasma concentrations. To widen the spectrum of CBDV possible mechanisms of action, electrophysiological methods were applied to investigate whether it could exert some effects on γ‐aminobutyric acid (GABA)A receptors. Our experiments showed that, in human hippocampal tissues of four patients affected by drug‐resistant temporal lobe epilepsy (TLE) transplanted in Xenopus oocytes, there is decrease of current rundown (i.e., reduction of use‐dependent GABAA current) after prolonged exposure to CBDV. This result has been confirmed using a single case of Rasmussen encephalitis (RE). Our patient's electroclinical improvement supports the hypothesis that cannabis could actually represent an effective, well‐tolerated antiepileptic drug. Moreover, the experimental data suggest that CBDV may greatly contribute to cannabis anticonvulsant effect through its possible GABAergic action.
Gating the mechanical channel Piezo1

Piezo1 is a eukaryotic cation-selective mechanosensitive ion channel. To understand channel function in vivo, we first need to analyze and compare the response in the whole cell and the patch. In patches, Piezo1 inactivates and the current is fit well by a 3-state model with a single pressure-dependent rate. However, repeated stimulation led to an irreversible loss of inactivation. Remarkably, the loss of inactivation did not occur on a channel-by-channel basis but on all channels at the same time. Thus, the channels are in common mechanical domain. Divalent ions decreased the unitary conductance from ~68 pS to ~37 pS, irrespective of the cation species. Mg and Ca did not affect inactivation rates, but Zn caused a 3-fold slowing. CytochalasinD (cytoD) does not alter inactivation rates or the transition to the non-inactivating mode but does reduce the steady-state response. Whole-cell currents were similar to patch currents but also had significant differences. In contrast to the patch, cytoD inhibited the current suggesting that the activating forces were transmitted through the actin cytoskeleton. Hypotonic swelling that prestressed the cytoskeleton and the bilayer greatly increased the sensitivity of both control and cytoD cells so there are two pathways to transmit force to the channels. In contrast to patch, removing divalent ions decreased the whole-cell current. The difference between whole cell and patch properties provide new insights into our understanding of the Piezo1 gating mechanisms and cautions against generalization to in situ behavior.
A randomised controlled trial assessing the efficacy of co‐phenylcaine nasal spray in flexible transnasal pharyngolaryngoscopy

INTRODUCTION The aim of this study was to assess whether using co‐phenylcaine nasal spray before flexible transnasal pharyngolaryngoscopy results in reduced pain and discomfort during the procedure. METHODS This was a randomised controlled trial. Eighty‐four patients were randomised to receive either co‐phenylcaine nasal spray or placebo nasal spray before performing transnasal flexible pharyngolaryngoscopy. Patient reported outcome measures included pain, discomfort, unpleasantness and willingness to repeat the procedure while clinician reported outcome measures comprised ease of examination and quality of view obtained during the procedure. RESULTS There was no statistically significant difference in scores for pain, discomfort, unpleasantness and willingness to repeat the procedure between the co‐phenylcaine and placebo groups. On the other hand, ease of examination scores were significantly better for the co‐phenylcaine group than for the placebo group. CONCLUSIONS The majority of patients do not find flexible pharyngolaryngoscopy unpleasant or painful with or without topical nasal anaesthesia. However, the spray does appear to help the examiner in completing a satisfactory assessment.
An Antibody to Notch2 Reverses the Osteopenic Phenotype of Hajdu-Cheney Mutant Male Mice

Notch receptors play a central role in skeletal development and bone remodeling. Hajdu-Cheney syndrome (HCS), a disease characterized by osteoporosis and fractures, is associated with gain-of-NOTCH2 function mutations. To study HCS, we created a mouse model harboring a point 6955C>T mutation in the Notch2 locus upstream of the proline, glutamic acid, serine, and threonine domain, leading to a Q2319X change at the amino acid level. Notch2Q2319X heterozygous mutants exhibited cancellous and cortical bone osteopenia. Microcomputed tomography demonstrated that the cancellous and cortical osteopenic phenotype was reversed by the administration of antibodies generated against the negative regulatory region (NRR) of Notch2, previously shown to neutralize Notch2 activity. Bone histomorphometry revealed that anti-Notch2 NRR antibodies decreased the osteoclast number and eroded surface in cancellous bone of Notch2Q2319X mice. An increase in osteoclasts on the endocortical surface of Notch2Q2319X mice was not observed in the presence of anti-Notch2 NRR antibodies. The anti-Notch2 NRR antibody decreased the induction of Notch target genes and Tnfsf11 messenger RNA levels in bone extracts and osteoblasts from Notch2Q2319X mice. In vitro experiments demonstrated increased osteoclastogenesis in Notch2Q2319X mutants in response to macrophage colony-stimulating factor and receptor activator of nuclear factor-κB ligand, and these effects were suppressed by the anti-Notch2 NRR. In conclusion, Notch2Q2319X mice exhibit cancellous and cortical bone osteopenia that can be corrected by the administration of anti-Notch2 NRR antibodies.
Frontoparietal activation during visual conjunction search: Effects of bottom‐up guidance and adult age

We conducted functional magnetic resonance imaging (fMRI) with a visual search paradigm to test the hypothesis that aging is associated with increased frontoparietal involvement in both target detection and bottom‐up attentional guidance (featural salience). Participants were 68 healthy adults, distributed continuously across 19 to 78 years of age. Frontoparietal regions of interest (ROIs) were defined from resting‐state scans obtained prior to task‐related fMRI. The search target was defined by a conjunction of color and orientation. Each display contained one item that was larger than the others (i.e., a size singleton) but was not informative regarding target identity. Analyses of search reaction time (RT) indicated that bottom‐up attentional guidance from the size singleton (when coincident with the target) was relatively constant as a function of age. Frontoparietal fMRI activation related to target detection was constant as a function of age, as was the reduction in activation associated with salient targets. However, for individuals 35 years of age and older, engagement of the left frontal eye field (FEF) in bottom‐up guidance was more prominent than for younger individuals. Further, the age‐related differences in left FEF activation were a consequence of decreasing resting‐state functional connectivity in visual sensory regions. These findings indicate that age‐related compensatory effects may be expressed in the relation between activation and behavior, rather than in the magnitude of activation, and that relevant changes in the activation‐RT relation may begin at a relatively early point in adulthood. Hum Brain Mapp 38:2128–2149, 2017. © 2017 Wiley Periodicals, Inc.
Clinically Relevant Levels of 4-Aminopyridine Strengthen Physiological Responses in Intact Motor Circuits in Rats, Especially After Pyramidal Tract Injury

Background. 4-Aminopyridine (4-AP) is a Food and Drug Administration–approved drug to improve motor function in people with multiple sclerosis. Preliminary results suggest the drug may act on intact neural circuits and not just on demyelinated ones. Objective. To determine if 4-AP at clinically relevant levels alters the excitability of intact motor circuits. Methods. In anesthetized rats, electrodes were placed over motor cortex and the dorsal cervical spinal cord for electrical stimulation, and electromyogram electrodes were inserted into biceps muscle to measure responses. The motor responses to brain and spinal cord stimulation were measured before and for 5 hours after 4-AP administration both in uninjured rats and rats with a cut lesion of the pyramidal tract. Blood was collected at the same time as electrophysiology to determine drug plasma concentration with a goal of 20 to 100 ng/mL. Results. We first determined that a bolus infusion of 0.32 mg/kg 4-AP was optimal: it produced on average 61.5 ± 1.8 ng/mL over the 5 hours after infusion. This dose of 4-AP increased responses to spinal cord stimulation by 1.3-fold in uninjured rats and 3-fold in rats with pyramidal tract lesion. Responses to cortical stimulation also increased by 2-fold in uninjured rats and up to 4-fold in the injured. Conclusion. Clinically relevant levels of 4-AP strongly augment physiological responses in intact circuits, an effect that was more robust after partial injury, demonstrating its broad potential in treating central nervous system injuries.
Non-technical skills and gastrointestinal endoscopy: a review of the literature

Background Non-technical skills (NTS) have gained increasing recognition in recent years for their role in safe, effective team performance in healthcare. Gastrointestinal endoscopy is a procedure-based specialty with rapidly advancing technology, significant operational pressures and rapidly changing ‘teams of experts’. However, to date there has been little focus on the effect of NTS in this field. Objectives This review aims to examine the existing literature on NTS in gastrointestinal endoscopy and identify areas for further research. Method A systematic search of MEDLINE, Embase, Cochrane Library, PsychINFO, CINAHL Plus and PubMed databases was performed using search terms Non-Technical Skills, Team Performance or Team Skills, and Endoscopy, Colonoscopy, OGD, Gastroscopy, Endoscopic Retrograde Cholangio-Pancreatography or Endoscopic Ultrasound. Results Eighteen relevant publications were found. NTS are deemed an essential component of practice, but so far there is little evidence of their integration into training or competency assessment. Those studies examining the effects of NTS and team training in endoscopy are small and have variable outcome measures with limited evidence of improvement in skills or clinical outcomes. NTS assessment in endoscopy is in its early phases with a few tools in development. Conclusions The current literature on NTS in gastrointestinal endoscopy is limited. NTS, however, are deemed an essential component of practice, with potential positive effects on team performance and clinical outcomes. A validated reliable tool would enable evaluation of training and investigation into the effects of NTS on outcomes. There is a clear need for further research in this field.
Character Disposition and Behavior Type: Influences of Valence on Preschool Children's Social Judgments

ABSTRACT The authors studied the influences of valence information on preschool children's (n = 47) moral (good or bad), liking (liked or disliked by a friend), and consequence-of-behavior (reward or punishment) judgments. The authors presented 8 scenarios describing the behavior valence, positive valence (help, share), negative valence (verbal insult, physical aggression), and disposition valence (nice or mean) of characters in social interaction with a friend. Overall, character disposition and behavior valence significantly influenced children's judgments. Moral, liking, and consequence-of-behavior judgments varied significantly by character disposition for both positive behavior scenarios. In contrast, there were fewer significant findings as a function of character disposition for negative behavior scenarios, suggesting that the negative behavior cue somewhat diminished the effect of character disposition on children's judgments. The authors discuss preschool students’ coordination of information about valence of behavior and character disposition and the students’ reluctance to judge that misbehavior warrants punitive consequence.
Serum cystatin C as a marker of renal function in detection of early acute kidney injury

In patients with acute kidney injury (AKI), serum creatinine level does not increase until moderate to severe reduction in glomerular filtration rate (GFR) occurs. Thus its use for estimating GFR in early AKI delays detection of kidney damage and making important therapeutic decisions. Moreover, serum cystatin C is not affected by gender, age, race, and muscle mass and also does not suffer from lag period for its rise in early AKI. We studied 200 healthy subjects and 130 AKI patients over a period of 2 years at a tertiary care hospital. Serum creatinine and serum cystatin C were studied and analyzed in relevance to early AKI. We found that 56.2% of patients of AKI group had normal levels of serum creatinine in early phase, while all patients had elevated serum cystatin C at same time. Multiple logistic regression analysis revealed cystatin C-based GFR reflecting decline in GFR with worsening AKI in better than creatinine-based GFR. Serum cystatin C is a better marker of renal function in early stages of AKI and is less affected by age, gender, muscle mass, and ethnicity. Its use helps in early therapeutic intervention and possibly favorable outcome.
In Sickness but Not in Wealth

We present results from a hypothetical framed field experiment assessing whether risk preferences significantly differ across the health and financial domains when they are elicited through the same multiple price list paired-lottery method. We consider a sample of 300 patients attending outpatient clinics in a university hospital in Athens during the Greek financial crisis. Risk preferences in finance were elicited using paired-lottery questions with hypothetical payments. The questions were adapted to the health domain by framing the lotteries as risky treatments in hypothetical health care scenarios. Using maximum likelihood methods, we estimated the degree of risk aversion, allowing for the estimates to be dependent on domain and individual characteristics. The subjects in our sample, who were exposed to both health and financial distress, tended to be less risk averse in the financial domain than in the health domain.