Miracle-dz/UniFAR-FTUs huggingface dataset:
The big and intricate dreams of little organelles: Embracing complexity in the study of membrane traffic

Compartmentalization of eukaryotic cells into dynamic organelles that exchange material through regulated membrane traffic governs virtually every aspect of cellular physiology including signal transduction, metabolism and transcription. Much has been revealed about the molecular mechanisms that control organelle dynamics and membrane traffic and how these processes are regulated by metabolic, physical and chemical cues. From this emerges the understanding of the integration of specific organellar phenomena within complex, multiscale and nonlinear regulatory networks. In this review, we discuss systematic approaches that revealed remarkable insight into the complexity of these phenomena, including the use of proximity‐based proteomics, high‐throughput imaging, transcriptomics and computational modeling. We discuss how these methods offer insights to further understand molecular versatility and organelle heterogeneity, phenomena that allow a single organelle population to serve a range of physiological functions. We also detail on how transcriptional circuits drive organelle adaptation, such that organelles may shift their function to better serve distinct differentiation and stress conditions. Thus, organelle dynamics and membrane traffic are functionally heterogeneous and adaptable processes that coordinate with higher‐order system behavior to optimize cell function under a range of contexts. Obtaining a comprehensive understanding of organellar phenomena will increasingly require combined use of reductionist and system‐based approaches.
In vivo formaldehyde cross-linking: it is time for black box analysis

Abstract Formaldehyde cross-linking is an important component of many technologies, including chromatin immunoprecipitation and chromosome conformation capture. The procedure remains empirical and poorly characterized, however, despite a long history of its use in research. Little is known about the specificity of in vivo cross-linking, its efficiency and chemical adducts induced by the procedure. It is time to search this black box.
Involvement of AtPolλ in the Repair of High Salt- and DNA Cross-Linking Agent-Induced Double Strand Breaks in Arabidopsis1[C][W]

DNA Pol λ participates in the repair of double strand breaks induced by high salinity and DNA cross-linking agent in Arabidopsis seedlings, demonstrating the importance of Pol λ in the double strand break repair signaling network in higher plant genome. DNA polymerase λ (Pol λ) is the sole member of family X DNA polymerase in plants and plays a crucial role in nuclear DNA damage repair. Here, we report the transcriptional up-regulation of Arabidopsis (Arabidopsis thaliana) AtPolλ in response to abiotic and genotoxic stress, including salinity and the DNA cross-linking agent mitomycin C (MMC). The increased sensitivity of atpolλ knockout mutants toward high salinity and MMC treatments, with higher levels of accumulation of double strand breaks (DSBs) than wild-type plants and delayed repair of DSBs, has suggested the requirement of Pol λ in DSB repair in plants. AtPolλ overexpression moderately complemented the deficiency of DSB repair capacity in atpolλ mutants. Transcriptional up-regulation of major nonhomologous end joining (NHEJ) pathway genes KU80, X-RAY CROSS COMPLEMENTATION PROTEIN4 (XRCC4), and DNA Ligase4 (Lig4) along with AtPolλ in Arabidopsis seedlings, and the increased sensitivity of atpolλ-2/atxrcc4 and atpolλ-2/atlig4 double mutants toward high salinity and MMC treatments, indicated the involvement of NHEJ-mediated repair of salinity- and MMC-induced DSBs. The suppressed expression of NHEJ genes in atpolλ mutants suggested complex transcriptional regulation of NHEJ genes. Pol λ interacted directly with XRCC4 and Lig4 via its N-terminal breast cancer-associated C terminus (BRCT) domain in a yeast two-hybrid system, while increased sensitivity of BRCT-deficient Pol λ-expressing transgenic atpolλ-2 mutants toward genotoxins indicated the importance of the BRCT domain of AtPolλ in mediating the interactions for processing DSBs. Our findings provide evidence for the direct involvement of DNA Pol λ in the repair of DSBs in a plant genome.
Mobile phone use in Cameroon: An increasingly useful tool for the follow‐up of children with Burkitt lymphoma

To the Editor: As workers providing treatment and follow-up for children with Burkitt lymphoma (BL) cases in three hospitals in Cameroon, we have observed that ownership of mobile phones by the parents of our patients has been on the increase in the last few years. It was routinely noted in all patients’ medical notes from admission, whether or not a mobile phone was owned. We suspected that mobile phones might be a useful tool in follow-up of our BL cases. In January 2011, we systematically reviewed the records of all BL admissions at two hospitals in NW Cameroon for the years 2007–2010; a total of 285 case records. We found that parent ownership of mobile phones increased from 20% in 2007 to 60% in 2010. We also determined that 29% successful contacts had been achieved by mobile phones to parents in 2007 compared with 82% successful contacts in 2010. Additionally, we found that recharging of the phones was not a problem, even in remote areas. We believe that follow-up of patients with BL using mobile phones is useful in this respect. Time and expense in visits, to the rural homes of our patients, by nursing/medical staff and hospital drivers is minimised; abandonment is ameliorated; patient status can readily be ascertained; lives may be saved. To this end, we intend to provide mobile phones to all parents of our newly diagnosed patients with BL who do not possess a mobile phone. This study was presented at SIOP Auckland 2011. Reference: SIOP Abstract; Auckland, NZ; Poster PC008; p. 775.
Visual Function in Preterm Infants without Major Retinopathy of Prematurity or Neurological Complications

Abstract Objective Early exposure of preterm infants to visual stimulation could affect the process of visual maturation. The aim of this study was to assess the impact of prematurity on visual function at 15 months post-term. Subjects and Methods Visual function was assessed in 102 preterm (PTI) and 50 full-term infants (FTI) without major cerebral pathology or retinopathy of prematurity (ROP) of grade 2 to 5, at 15 months' corrected age. The visual acuity, refractive status, contrast sensitivity, strabismus, fundus, and neurodevelopment were examined. Results Impairments of individual visual functions were 2 to 10 times more common in PTI than FTI. However, the difference was significant only for refractive errors (p = 0.007, odds ratio [OR] = 10.5). The incidence of visual deficits was higher in PTI with gestational age less than 32 weeks compared with PTI with higher gestational age (OR = 1.3 to 2.0), but not significantly. Of the PTI, 4.9%, 2.9%, and 10.8% had mild abnormalities on ultrasound scans, neuromotor, and developmental examination, respectively, which were not associated with increased incidence of visual deficits. Conclusion Premature exposure to visual stimulation does not induce visual maturation but it is associated with impairment of certain aspects of visual function even in the absence of major ROP or neurodevelopmental deficits.
Influence of provider mix and regulation on primary care services supplied to US patients

Abstract Access to medical care and how it differs for various patients remain key policy issues. While existing work has examined clinic structure’s influence on productivity, less research has explored the link between provider mix and access for different patient types – which also correspond to different service prices. We exploit experimental data from a large field study spanning 10 US states where trained audit callers were randomly assigned an insurance status and then contacted primary care physician practices seeking new patient appointments. We find clinics with more non-physician clinicians are associated with better access for Medicaid patients and lower prices for office visits; however, these relationships are only found in states granting full practice autonomy to these providers. Substituting more non-physician labor in primary care settings may facilitate greater appointment availability for Medicaid patients, but this likely rests on a favorable policy environment. Relaxing regulations for non-physicians may be an important initiative as US health reforms continue and also relevant to other countries coping with greater demands for medical care and related financial strain.
GDSL LIPASE1 Modulates Plant Immunity through Feedback Regulation of Ethylene Signaling1[W]

A GDSL lipase regulates ethylene-dependent pathogen resistance and ethylene-salicylic acid signaling interactions in plants. Ethylene is a key signal in the regulation of plant defense responses. It is required for the expression and function of GDSL LIPASE1 (GLIP1) in Arabidopsis (Arabidopsis thaliana), which plays an important role in plant immunity. Here, we explore molecular mechanisms underlying the relationship between GLIP1 and ethylene signaling by an epistatic analysis of ethylene response mutants and GLIP1-overexpressing (35S:GLIP1) plants. We show that GLIP1 expression is regulated by ethylene signaling components and, further, that GLIP1 expression or application of petiole exudates from 35S:GLIP1 plants affects ethylene signaling both positively and negatively, leading to ETHYLENE RESPONSE FACTOR1 activation and ETHYLENE INSENSITIVE3 (EIN3) down-regulation, respectively. Additionally, 35S:GLIP1 plants or their exudates increase the expression of the salicylic acid biosynthesis gene SALICYLIC ACID INDUCTION-DEFICIENT2, known to be inhibited by EIN3 and EIN3-LIKE1. These results suggest that GLIP1 regulates plant immunity through positive and negative feedback regulation of ethylene signaling, and this is mediated by its activity to accumulate a systemic signal(s) in the phloem. We propose a model explaining how GLIP1 regulates the fine-tuning of ethylene signaling and ethylene-salicylic acid cross talk.
Monoubiquitination of Histone 2B at the Disease Resistance Gene Locus Regulates Its Expression and Impacts Immune Responses in Arabidopsis1[C][W][OPEN]

Histone modification at the plant immune receptor gene modulates immune responses in Arabidopsis. Disease resistance (R) genes are key components in plant immunity. Here, we show that Arabidopsis (Arabidopsis thaliana) E3 ubiquitin ligase genes HISTONE MONOUBIQUITINATION1 (HUB1) and HUB2 regulate the expression of R genes SUPPRESSOR OF npr1-1, CONSTITUTIVE1 (SNC1) and RESISTANCE TO PERONOSPORA PARASITICA4. An increase of SNC1 expression induces constitutive immune responses in the bonzai1 (bon1) mutant, and the loss of HUB1 or HUB2 function reduces SNC1 up-regulation and suppresses the bon1 autoimmune phenotypes. HUB1 and HUB2 mediate histone 2B (H2B) monoubiquitination directly at the SNC1 R gene locus to regulate its expression. In addition, SNC1 and HUB1 transcripts are moderately up-regulated by pathogen infection, and H2B monoubiquitination at SNC1 is enhanced by pathogen infection. Together, this study indicates that H2B monoubiquitination at the R gene locus regulates its expression and that this histone modification at the R gene locus has an impact on immune responses in plants.
Additional Amphivasal Bundles in Pedicel Pith Exacerbate Central Fruit Dominance and Induce Self-Thinning of Lateral Fruitlets in Apple1[C][W]

Amphivasal bundles in dominant fruits support a role in the subsequent self-abscission of lateral fruits. Apple (Malus × domestica) trees naturally produce an excess of fruitlets that negatively affect the commercial value of fruits brought to maturity and impact their capacity to develop flower buds the following season. Therefore, chemical thinning has become an important cultural practice, allowing the selective removal of unwanted fruitlets. As the public pressure to limit the use of chemical agents increases, the control of thinning becomes a major issue. Here, we characterized the self-thinning capacity of an apple hybrid genotype from the tree scale to the molecular level. Additional amphivasal vascular bundles were identified in the pith of pedicels supporting the fruitlets with the lowest abscission potential (central fruitlet), indicating that these bundles might have a role in the acquisition of dominance over lateral fruitlets. Sugar content analysis revealed that central fruitlets were better supplied in sorbitol than lateral fruitlets. Transcriptomic profiles allowed us to identify genes potentially involved in the overproduction of vascular tissues in central pedicels. In addition, histological and transcriptomic data permitted a detailed characterization of abscission zone development and the identification of key genes involved in this process. Our data confirm the major role of ethylene, auxin, and cell wall-remodeling enzymes in abscission zone formation. The shedding process in this hybrid appears to be triggered by a naturally exacerbated dominance of central fruitlets over lateral ones, brought about by an increased supply of sugars, possibly through additional amphivasal vascular bundles. The characterization of this genotype opens new perspectives for the selection of elite apple cultivars.
Stomatal Size, Speed, and Responsiveness Impact on Photosynthesis and Water Use Efficiency1[C]

Analysis of stomatal parameters highlights strategies to improve stomatal control of gas exchange and transpiration for enhanced water use efficiency without compromising CO2 uptake for photosynthesis. The control of gaseous exchange between the leaf and bulk atmosphere by stomata governs CO2 uptake for photosynthesis and transpiration, determining plant productivity and water use efficiency. The balance between these two processes depends on stomatal responses to environmental and internal cues and the synchrony of stomatal behavior relative to mesophyll demands for CO2. Here we examine the rapidity of stomatal responses with attention to their relationship to photosynthetic CO2 uptake and the consequences for water use. We discuss the influence of anatomical characteristics on the velocity of changes in stomatal conductance and explore the potential for manipulating the physical as well as physiological characteristics of stomatal guard cells in order to accelerate stomatal movements in synchrony with mesophyll CO2 demand and to improve water use efficiency without substantial cost to photosynthetic carbon fixation. We conclude that manipulating guard cell transport and metabolism is just as, if not more likely to yield useful benefits as manipulations of their physical and anatomical characteristics. Achieving these benefits should be greatly facilitated by quantitative systems analysis that connects directly the molecular properties of the guard cells to their function in the field.
New Dried Human Amniotic Membrane Is Useful as a Substitute for Dural Repair after Skull Base Surgery

Abstract Objectives Cerebrospinal fluid (CSF) leakage is an undesirable complication of skull base surgery. We used dried human amniotic membrane (AM) as a patch graft for dural repair to determine its efficacy in preventing CSF leakage. Design Frontoparietal craniotomy and removal of dura were performed in 20 Wistar rats. A dried AM was placed to cover the dural defect without suturing in 16 animals. In four animals, an expanded polytetrafluoroethylene was implanted. At 2 weeks and 1, 3, and 6 months, histological examination was performed. Dried AM was also used as a substitute in 10 patients who underwent skull base surgery, after approval by the Ethics Committee of the University of Toyama. Results At 2 weeks after implantation, thick connective tissue completely enclosed the dried AM. At 1 month after implantation, the connective tissue became thin and the implanted AM shortened. At 3 and 6 months after implantation, histological examination revealed disappearance of the dried AM and formation of membranous tissue. In the clinical study, neither CSF leakage nor clinical adverse reactions directly related to the dried AM were observed. Conclusion Dried human AM appears to be an ideal substitute for dura, since it is replaced by natural tissue.
Natural Compounds as Next-Generation Herbicides

Natural products are an important resource in the discovery of herbicides. Herbicides with new modes of action (MOAs) are badly needed due to the rapidly evolving resistance to commercial herbicides, but a new MOA has not been introduced in over 20 years. The greatest pest management challenge for organic agriculture is the lack of effective natural product herbicides. The structural diversity and evolved biological activity of natural phytotoxins offer opportunities for the development of both directly used natural compounds and synthetic herbicides with new target sites based on the structures of natural phytotoxins. Natural phytotoxins are also a source for the discovery of new herbicide target sites that can serve as the focus of traditional herbicide discovery efforts. There are many examples of strong natural phytotoxins with MOAs other than those used by commercial herbicides, which indicates that there are molecular targets of herbicides that can be added to the current repertoire of commercial herbicide MOAs.
Biomechanical performance measurement using wireless inertial sensors for professional and recreational darts players

Biomechanical performance is an important factor for developing darts players. The darts throw happens so quickly (< 200 ms) that even the trained eye of an experienced coach has difficulty in identifying the small movement differences that can determine a player's technical proficiency. Traditionally for high precision sports such as darts, biomechanical information is captured with an optical marker system, which is immobile, expensive and requires a specialised team to operate. Advances in wearable sensor technology allow measurement of kinematics using non-invasive sensors embedded in athletic clothing. Data from one professional player aged 24 y and ranked within the top 60 in the Professional Darts Corporation world rankings and two recreational players aged 28 and 25 y respectively were used in this analysis. A single custom-built Wireless Inertial Measurement Unit (WIMU) was placed on the proximal forearm of each participant. Each player performed 150 throws in a real game situation. Score and the projectile's final position on the target were recorded manually. As reported previously, players with higher skill level had the ability to regulate a number of variable parameters affecting outcome, for each discrete over arm throwing action, more effectively then the less skilled players. These parameters included the maximum acceleration of the throwing arm (std. dev. Pro. 0.1 g, Rec 0.35 g), the maximum speed of the throwing arm (std. dev. Pro. 0.1 ms-1 g, Rec 0.2 ms-1), and the throw timing (std. dev. Pro. 0.15 s, Rec 0.67 s). These results concur with previous measurements taken using an optical marker system. Placing WIMU's on a darts player's arm holds potential for coaches to easily measure biomechanical factors, thus quantifying performance without the need for a complex biomechanics laboratory. Coaches can use this data to fine-tune elite athletes or to screen younger players for characteristics that are indicative of a potential for high performance.
Takayasu Arteritis and Pregnancy: Case Report and Review of the Literature

Takayasu arteritis is a rare primary vasculitis of unknown cause, primarily affecting women of child-bearing age. Its course is unpredictable, but slow progression is usual, leading to stenosis, occlusion, or aneurysmal degeneration of the aorta or its major branches. Poor prognostic factors include retinopathy, secondary hypertension, aortic regurgitation, and arterial aneurysms. Pharmacological treatment is aimed at controlling vessel inflammation and hypertension. We describe the course and management of pregnancy in a woman with severe, complicated Takayasu’s arteritis and review this disease with special reference to natural history, etiopathogenesis, diagnostic criteria, classification, prognostic factors, and treatment strategies. Target Audience: Obstetricians & Gynecologists, Family Physicians Leaning Objectives: After completion of this article, the reader should be able to recall the symptoms and hallmarks of Takayasu arteritis, identify potential treatment strategies for Takayasu arteritis in pregnancy, and summarize predictors of poor pregnancy outcomes in women with Takayasu arteritis.
The symbolic roots of blood donation

Throughout history, blood has been embedded with powerful and paradoxical connotations. In the last decades, a more rational conception based on scientific knowledge has emerged, portraying blood as a “disenchanted” and utilitarian object, hence more apt for donation between strangers. This study aims to examine blood's representations in Quebec, Canada.
Strategien zur Prävention des hepatozellulären Karzinoms bei der Hepatitis-Virus-Infektion

Liver cirrhosis induced by HBV and HCV infections is the main risk factor for the development of hepatocellular carcinoma (HCC). Therefore, prevention of chronic infection with hepatitis viruses and prevention of the development of cirrhosis are essential for the primary prevention of HCC. A consequent vaccination program for HBV is suitable to reduce the rate of infections and the HCC-associated mortality. Since no vaccine is available for HCV, the reduction of risky behaviour and the improvement of hygiene standards are the mainstays for prevention of HCV. An efficient antiviral therapy aimed at the durable suppression of the viral load reduces the risk of progression to cirrhosis and development of HCC in precirrhotic stages of chronic HBV or HCV infections. In cirrhotic patients, the risk of developing HCC remains elevated even if a sustained virological response is achieved, thus requiring further screening with the intention of the early detection of HCC. It is too early to judge whether virological nonresponders profit from continued antiviral therapy. Therefore, the early diagnosis of chronic HBV or HCV infection is the single most important factor for the prevention of HCC. Secondary prevention after surgical resection or local ablative therapy may reduce the frequency of late recurrence. Liver transplantation is today the most effective measure of secondary prevention for selected patients with HCC. Due to its antiproliferative effects, the immunosuppressive drug sirolimus may play a role for secondary prevention of HCC following transplantation.