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"Graham, Robert J"
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مصور في الحج : رحلات محمد علي أفندي السعودي (1904-1908)
يعد كتاب مصور في الحج تأريخا مصورا لرحلة الحج والأماكن المقدسة في مكة المكرمة والمدينة المنورة وتعكس يوميات المصور محمد علي أفندي السعودي وهي موضوع هذا الكتاب رؤية نادرة عبر عينين مصريتين لرحلة الحج التي قامت بها الحملة المصرية في مطلع القرن العشرين إبان حكم الإمبراطورية العثمانية وبتزامن مع تشييد سكة الحجاز الحديدية التي ستغير طرق الحج المعتادة.
BOOK
Mitochondrial fusion is required for spermatogonial differentiation and meiosis
Differentiating cells tailor their metabolism to fulfill their specialized functions. We examined whether mitochondrial fusion is important for metabolic tailoring during spermatogenesis. Acutely after depletion of mitofusins Mfn1 and Mfn2 , spermatogenesis arrests due to failure to accomplish a metabolic shift during meiosis. This metabolic shift includes increased mitochondrial content, mitochondrial elongation, and upregulation of oxidative phosphorylation (OXPHOS). With long-term mitofusin loss, all differentiating germ cell types are depleted, but proliferation of stem-like undifferentiated spermatogonia remains unaffected. Thus, compared with undifferentiated spermatogonia, differentiating spermatogonia and meiotic spermatocytes have cell physiologies that require high levels of mitochondrial fusion. Proteomics in fibroblasts reveals that mitofusin-null cells downregulate respiratory chain complexes and mitochondrial ribosomal subunits. Similarly, mitofusin depletion in immortalized spermatocytes or germ cells in vivo results in reduced OXPHOS subunits and activity. We reveal that by promoting OXPHOS, mitofusins enable spermatogonial differentiation and a metabolic shift during meiosis.
Journal Article
Batman, Knightsend
\"Bruce Wayne returns to Gotham City only to find that his replacement, Jean-Paul Valley, has become increasingly violent and reckless. Now he must confront and defeat Jean-Paul in order to win back the mantle of the Bat. Following the events of Batman: Knightquest: The Search, Bruce Wayne is ready to return to his role as Gotham's greatest protector, Batman. Including never-before-collected material! Bruce Wayne completes his improbable recovery from his broken back and is ready to resume his role as Gotham's protector. But Jean-Paul Valley, the man who now patrols the night as a vicious and violent Batman, is not willing to give up his new identity. Driven to the brink of madness by inner demons, the new Batman seeks to destroy Bruce as they meet in mortal combat.\"-- Provided by publisher.
Book
Novel integrated computational AMP discovery approaches highlight diversity in the helminth AMP repertoire
Antimicrobial Peptides (AMPs) are immune effectors that are key components of the invertebrate innate immune system providing protection against pathogenic microbes. Parasitic helminths (phylum Nematoda and phylum Platyhelminthes) share complex interactions with their hosts and closely associated microbiota that are likely regulated by a diverse portfolio of antimicrobial immune effectors including AMPs. Knowledge of helminth AMPs has largely been derived from nematodes, whereas the flatworm AMP repertoire has not been described. This study highlights limitations in the homology-based approaches, used to identify putative nematode AMPs, for the characterisation of flatworm AMPs, and reveals that innovative algorithmic AMP prediction approaches provide an alternative strategy for novel helminth AMP discovery. The data presented here: (i) reveal that flatworms do not encode traditional lophotrochozoan AMP groups (Big Defensin, CSαβ peptides and Myticalin); (ii) describe a unique integrated computational pipeline for the discovery of novel helminth AMPs; (iii) reveal >16,000 putative AMP-like peptides across 127 helminth species; (iv) highlight that cysteine-rich peptides dominate helminth AMP-like peptide profiles; (v) uncover eight novel helminth AMP-like peptides with diverse antibacterial activities, and (vi) demonstrate the detection of AMP-like peptides from Ascaris suum biofluid. These data represent a significant advance in our understanding of the putative helminth AMP repertoire and underscore a potential untapped source of antimicrobial diversity which may provide opportunities for the discovery of novel antimicrobials. Further, unravelling the role of endogenous worm-derived antimicrobials and their potential to influence host-worm-microbiome interactions may be exploited for the development of unique helminth control approaches.
Journal Article
Batman Knightfall omnibus
\"This classic storyline that led to the birth of a new Batman begins as the Dark Knight's greatest enemies have all simultaneously escaped from Arkham Asylum and are preying on Gotham City. With his city under siege, Batman pushes his body to its physical breaking point as he takes on the Joker, the Mad Hatter, Poison Ivy, Killer Croc, the Riddler and the Scarecrow, one after another. But things get much worse, when Bane, the man behind all of this madness, confronts an exhausted Batman and cripples him by breaking his back.\"-- Provided by publisher.
Book
Dysphagia Phenotypes in Spinal Muscular Atrophy: The Past, Present, and Promise for the Future
Purpose The aim of this study was to provide clinicians with an overview of literature relating to dysphagia in spinal muscular atrophy (SMA) to guide assessment and treatment. Method In this clinical focus article, we review literature published in Scopus and PubMed between 1990 and 2020 pertaining to dysphagia in SMA across the life span. Original research articles that were published in English were included. Searches were conducted within four themes of inquiry: (a) etiology and phenotypes, (b) respiratory systemic deficits and management, (c) characteristics of natural history dysphagia and its treatment, and (d) dysphagia outcomes with disease-modifying therapies. Articles for the first two themes were selected by content experts who identified the most salient articles that would provide clinicians foundational background knowledge about SMA. Articles for the third theme were identified using search terms, including
OR
. Search terms for the fourth theme included
AND
OR
. Review of Pertinent Literature Twenty-nine articles were identified. Findings across identified articles support the fact that patients with SMA who do not receive disease-modifying therapy exhibit clinically significant deficits in oropharyngeal swallow function. Few investigations provided systematic information regarding the underlying physiological deficits responsible for this loss in function, the timing of the degradation, or how disease-modifying therapies change these outcomes. Conclusion Future research outlining the physiological and functional oropharyngeal swallowing deficits among patients with SMA who receive disease-modifying therapy is critical in developing standards of dysphagia care to guide clinicians.
Journal Article
A real-world analysis of the impact of X-linked myotubular myopathy on caregivers in the United States
Background
X-linked myotubular myopathy (XLMTM) is a rare, life-threatening congenital myopathy with multisystem involvement, which often includes the need for invasive ventilator support, gastrostomy tube feeding, and wheelchair use in approximately 80% of patients. The direct and indirect financial impact of extensive supportive care, as reported by caregivers of individuals with XLMTM, and the health-related quality of life (HRQoL) of caregivers has not been previously described. Here, we use a survey co-designed by patient advocates to provide objective information on the physical and financial challenges of caregiving for individuals with XLMTM.
Methods
A real-world web-based survey was conducted in the United States between November 19, 2019, and January 23, 2020. The survey was developed in association with patient advocacy leaders from the XLMTM community, who were also caregivers of individuals with XLMTM. The survey included the EuroQol 5-dimension 5-level HRQoL instrument and visual analog scale, and a cost (direct and indirect medical costs) and healthcare resource questionnaire. The survey was shared among the XLMTM community by patient advocacy organizations. Caregivers who completed the survey and met the eligibility criteria were included. Descriptive statistics were conducted using Microsoft Excel.
Results
Twenty-two caregiver respondents agreed to participate. All respondents completed the cost and health resource survey. Productivity loss varied between participants over the prior 12 months. Durable medical equipment expenses comprised most of the direct medical out-of-pocket costs. Non-medical expenditures (e.g. home and vehicle modifications) were higher than direct medical out-of-pocket costs. Twelve of the 22 respondents completed the HRQoL survey. The HRQoL domains most impacted were usual activities, anxiety/depression, and pain/discomfort.
Conclusions
Findings from this real-world survey of caregivers for individuals with XLMTM describe the caregiver experience, as well as the multifaceted impact of the disease on caregiver productivity loss, out-of-pocket expenses, and HRQoL. XLMTM comes with financial constraints and substantial impacts on caregivers’ physical and mental health. Understanding these gaps is crucial to support the caregivers who provide care for this medically fragile population.
Journal Article
Resilience of Snowball Earth to Stochastic Events
Earth went through at least two periods of global glaciation (i.e., “Snowball Earth” states) during the Neoproterozoic, the shortest of which (the Marinoan) may not have lasted sufficiently long for its termination to be explained by the gradual volcanic build‐up of greenhouse gases in the atmosphere. Large asteroid impacts and supervolcanic eruptions have been suggested as stochastic geological events that could cause a sudden end to global glaciation via a runaway melting process. Here, we employ an energy balance climate model to simulate the evolution of Snowball Earth's surface temperature after such events. We find that even a large impactor (diameters of d ∼ 100 km) and the supervolcanic Toba eruption (74 Kyr ago), are insufficient to terminate a Snowball state unless background CO2 has already been driven to high levels by long‐term outgassing. We suggest, according to our modeling framework, that Earth's Snowball states would have been resilient to termination by stochastic events. Plain Language Summary The terminations of Earth's longest periods of global glaciation are commonly understood to have occurred due to the gradual build‐up of greenhouse gases in the atmosphere from volcanism. However, the sudden ends of Earth's shorter global glaciation periods likely cannot be explained by the same mechanisms. Large asteroid impacts and supervolcanic eruptions have been suggested as geophysical phenomena that could cause abrupt ends to global glaciation periods. Here, we model the evolution of the planet's surface temperature in the aftermath of such events. Impacts and eruptions open up gaps in the global ice sheet, and also partially cover the ice in far‐spreading dust and ash, both of which increase the amount of solar radiation that is absorbed by the planet comparing to the highly reflective surface of ice and snow. Greater absorption of radiation leads to higher surface temperatures, which increases ice melting, and generates a feedback loop that can melt the entire planet surface. However, we find that the scales of impact or eruption required to produce global melting are too great to have likely occurred at the times of Earth's global glaciations. Other mechanisms must, therefore, be explored to explain Earth's short glaciation periods. Key Points We use an Energy Balance Model (EBM) to simulate the response of Snowball climate after stochastic events Impact simulations and estimates of ash dispersion are used to inform initial conditions Earth's Snowball states seem resilient to termination by stochastic events within our modeling framework
Journal Article
The temporal dynamics of the tracheal microbiome in tracheostomised patients with and without lower respiratory infections
Airway microbiota dynamics during lower respiratory infection (LRI) are still poorly understood due, in part, to insufficient longitudinal studies and lack of uncontaminated lower airways samples. Furthermore, the similarity between upper and lower airway microbiomes is still under debate. Here we compare the diversity and temporal dynamics of microbiotas directly sampled from the trachea via tracheostomy in patients with (YLRI) and without (NLRI) lower respiratory infections.
We prospectively collected 127 tracheal aspirates across four consecutive meteorological seasons (quarters) from 40 patients, of whom 20 developed LRIs and 20 remained healthy. All aspirates were collected when patients had no LRI. We generated 16S rRNA-based microbial profiles (~250 bp) in a MiSeq platform and analyzed them using Mothur and the SILVAv123 database. Differences in microbial diversity and taxon normalized (via negative binomial distribution) abundances were assessed using linear mixed effects models and multivariate analysis of variance.
Alpha-diversity (ACE, Fisher and phylogenetic diversity) and beta-diversity (Bray-Curtis, Jaccard and Unifrac distances) indices varied significantly (P<0.05) between NLRI and YLRI microbiotas from tracheostomised patients. Additionally, Haemophilus was significantly (P = 0.009) more abundant in YLRI patients than in NLRI patients, while Acinetobacter, Corynebacterium and Pseudomonas (P<0.05) showed the inverse relationship. We did not detect significant differences in diversity and bacterial abundance among seasons. This result disagrees with previous evidence suggesting seasonal variation in airway microbiotas. Further study is needed to address the interaction between microbes and LRI during times of health and disease.
Journal Article
Identification of secreted bacterial proteins by noncanonical amino acid tagging
Pathogenic microbes have evolved complex secretion systems to deliver virulence factors into host cells. Identification of these factors is critical for understanding the infection process. We report a powerful and versatile approach to the selective labeling and identification of secreted pathogen proteins. Selective labeling of microbial proteins is accomplished via translational incorporation of azidonorleucine (Anl), a methionine surrogate that requires a mutant form of the methionyl-tRNA synthetase for activation. Secreted pathogen proteins containing Anl can be tagged by azide-alkyne cycloaddition and enriched by affinity purification. Application of the method to analysis of the type III secretion system of the human pathogen Yersinia enterocolitica enabled efficient identification of secreted proteins, identification of distinct secretion profiles for intracellular and extracellular bacteria, and determination of the order of substrate injection into host cells. This approach should be widely useful for the identification of virulence factors in microbial pathogens and the development of potential new targets for antimicrobial therapy.
Journal Article