Global mRNA translation may differ dramatically between progenitor cells and their differentiated progeny. One way cell type-specific translation is established is through ribosome concentration. In addition to addressing unique metabolic needs, changes in ribosome concentration may influence cell fate. The mechanisms that determine ribosome abundance in progenitors versus differentiated progeny are not fully understood. Here we investigated this process by focusing on ribosomal RNA (rRNA) synthesis in Drosophila neural progenitors and neurons. We found that rRNA synthesis is robust in neural progenitors but is limited in post-mitotic neurons. Newly born neurons inherit rRNA from their progenitor parent and this inherited rRNA is sufficient for protein synthesis in neurons. Our findings support a model in which neuron-specific translation programs are established by rRNA inheritance.
There has been an increased prevalence of Group B Streptococcal disease over the last two decades with a mortality rate of ∼25% for invasive infection. We report a patient whom we discovered Monoclonal B cell Lymphocytosis that led to disseminated GBS disease . Likely source was asymptomatic bacteriuria following TURP
Whole genomes are commonly assembled into a collection of scaffolds and often lack annotations of autosomes, sex chromosomes and, and organelle genomes (i.e., mitochondrial and chloroplast). As these chromosome types can have highly disparate evolutionary histories, it is imperative to take this information into account when analyzing genomic variation. Here we assessed the accuracy of four methods for identifying the homogametic sex chromosome using two whole genome sequenced (WGS) and 133 RAD sequenced white-tailed eagles (Haliaeetus albicilla): i) difference in read depth per scaffold, ii) heterozygosity per scaffold in a male and female bird, iii) mapping to a reference genome of a related species (chicken) with identified sex chromosomes, and iv) an analysis of SNP-loadings from a principal components analysis (PCA), based on low-depth RADseq data from 133 individuals. In i and ii, the WGS were mapped to a reference genome consisting of 1142 assembled scaffolds from the golden eagle (Aquila chrysaetos) with no identified chromosomes. The read depth per scaffold identified 86.41% of the homogametic sex chromosome (Z) with few false positives. The SNP-loading scores found 78.6% of the Z-chromosome but had a false positive discovery rate of more than 10%. The heterozygosity per scaffold did not provide clear results due to a lack of diversity in both the Z and autosomal chromosomes, and potential interference from the heterogametic sex chromosome (W).
Cylas formicarius is one of the most important pests of sweet potato worldwide, causing considerable ecological and economic damage. To improve the effect of comprehensive management and understanding of genetic mechanisms, the genetic functions of C. formicarius have been the subject of intensive study. Using Illumina and PacBio sequencing, we obtained a chromosome-level genome assembly of adult weevils from lines inbred for 15 generations. The high-quality assembly obtained had a size of 338.84 Mb, with contig and scaffold N50 values of 14.97 Mb and 34.23 Mb, respectively. In total, 157.51 Mb of repeat sequences and 11,907 protein-coding genes were predicted. A total of 337.06 Mb of genomic sequences was located on the 11 chromosomes, and the sequence length that could be used to determine the sequence and direction accounted for 99.03% of the total length of the associated chromosome. Comparative genomic analysis showed that C. formicarius was sister to Dendroctonus ponderosae, and C. formicarius diverged from D. ponderosae approximately 138.89 million years ago (Mya). Many important gene families that were expanded in the C. formicarius genome were involved in the chemosensory system. In an in-depth study, the binding assay results indicated that CforOBP4-6 had strong binding affinities for sex pheromones and other ligands. Overall, the high-quality C. formicarius genome provides a valuable resource to reveal the molecular ecological basis, genetic mechanism and evolutionary process of major agricultural pests, deepen the understanding of environmental adaptability and apparent plasticity, and provide new ideas and new technologies for ecologically sustainable pest control.
The effects of the discharge of wastewater treatment plants (WWTP) on the status of rivers have most commonly been focused on water quality. A very limited number of works have characterised the ability of treatment plants to modify flow patterns in the receiving rivers. This paper presents a methodology for the assessment of the hydrologic alteration caused by WWTP discharges, over a two-fold sequence. The first phase comprises the application of indicators derived from accessible data and informative of the capacity of treatment plants to produce significant flow alterations. The second phase, which may only be carried out when flow data in the receiving river is available, is based on the indicators of hydrologic alteration provided by the free software IAHRIS (6 indicators) and IHA (2 indicators), and on a new indicator proposed in this paper to obtain information of flow alteration at seasonal and monthly time scales. The procedure suggested in this work is applied to the Manzanares River (Central Spain), allowing the quantification of the flow alteration generated by the 12 WWTP which give service to Madrid city (3.8 million inhabitants): Large increases of annual water volumes (from 108 hm3 to 410 hm3); at a monthly scale (increase from 246% to 1516%); variability in flow decreases in wet years by up to 47% and increases in dry years by up to 380%; seasonal patterns is altered within an altered regime. Results of the analysis show: (i) the ability of the proposed methodology to characterise the modification of flow patterns due to WWTP discharges; (ii) the importance of assessing such changes when evaluating the environmental impact of treatment plants; (iii) the importance of designing preventive and mitigation measures which maintain the ecological integrity of river ecosystems in the receiving channels.
Immune modulation is a key therapeutic tool for allergic diseases and asthma. It can be achieved in an antigen-specific way via allergen immunotherapy (AIT) or in endotype-driven approach using biologicals that target the major pathways of the type 2 (T2) immune response: IgE, IL-5 and IL-4/IL-13. COVID-19 vaccine provides an excellent opportunity to tackle the global pandemics and is currently being applied in an accelerated rhythm worldwide. It works as well through immune modulation. Thus, as there is an obvious interference between these treatment modalities recommendations on how they should be applied in sequence are expected. The European Academy of Allergy and Clinical Immunology (EAACI) gathered an outstanding expert panel under its Research and Outreach Committee (ROC). This expert panel was called to evaluate the evidence and formulate recommendation on the administration of COVID-19 vaccine in patients with allergic diseases and asthma receiving AIT or biologicals. The panel also formulated recommendations for COVID-19 vaccine in association with biologicals targeting the type 1 or type 3 immune response. In formulating recommendations, the panel evaluated the mechanisms of COVID-19 infection, of COVID-19 vaccine, of AIT and of biologicals and considered the data published for other anti-infectious vaccines administered concurrently with AIT or biologicals.
Aims: The COVID-19 pandemic led to hospitals in the United Kingdom substituting face-to-face (FtF) clinics with virtual clinic (VC) appointments. We evaluated the impact of virtual two-week wait (2-ww) lower gastrointestinal (LGI) consultations on stakeholders at a district general hospital in England. Methods: Patients undergoing index outpatient 2-ww LGI clinic assessment between 01/06/2019-31/10/2019 (FtF group) and 01/06/2020-31/10/2020 (VC group) were identified. Relevant data were obtained using electronic patient records. Compliance with national cancer waiting time targets (WTT) was assessed. Environmental and financial impact analyses were performed. Results: In total, 1531 patients were analysed (median age=70, male=852, 55.6%). Of these, 757 (49.4%) were assessed virtually via telephone; the remainder were seen FtF (n=774, 50.6%). Ninety two (6%, VC=44, FtF=48) patients had malignant pathology and 64 (4.2%) had colorectal cancer (CRC); of these, 46 (71.9%, VC=26, FtF=20) underwent treatment with curative intent. The median waiting times to index appointment, investigation and diagnosis were significantly lower following VC assessment (p<0.001). The cancer detection rates (p=0.749), treatments received (p=0.785) and median time to index treatment for CRC patients (p=0.156) were similar. A significantly higher proportion of patients were seen within two weeks of referral in the VC group (p<0.001). VC appointments saved patients a total of 9288 miles, 0.7 metric tonnes of CO2 emissions and £7482.97. Taxpayers saved £80,242.00 from VCs. No adverse events or complaints were reported in the VC group. Conclusion: Virtual 2-ww LGI clinics were effective, safe and were associated with tangible environmental and financial benefits for stakeholders.
Needle-free Epicutaneous For t 2 DNA Vaccine is Effective for Preventing and Treating Biting Midge (Forcipomyia taiwana) allergy in a murine modelTo the Editor,Allergen-specific immunotherapy (ASIT) remains the only treatment capable of inducing immune tolerance to the corresponding allergen and potentially treating the root cause of the allergic disease.1 As the treatment course of protein-based vaccines for ASIT is time-consuming, an easily administered epicutaneous anti-allergic DNA-based vaccine is an attractive method, especially in light of the COVID-19 pandemic.2 We established a mouse model of biting midge allergy to test the concept of the epicutaneous DNA vaccine.The biting midge, Forcipomyia taiwana , is the most prevalent cause of biting insect allergy in Taiwan. It is a tiny hematophagous midge that attacks en masse. As many as 60% of exposed individuals develop allergic reactions to the bites.3 The midge is widely distributed throughout Taiwan and southern China. Among the identified allergens, For t 2 is the most predominant, with 75% of midge-allergic patients showing specific IgE to For t 2.4E.coli -expressed For t 2 recombinant protein (rFor t 2) was used as an allergen to sensitize and challenge the mice.5For t 2-encoding fragment (GenBank accession EU678971) was amplified by PCR. The PCR products were subcloned into pVAX1 (Life Technologies, Carlsbad, CA) . The experiments were designed using two approaches: therapeutic and prophylactic (Fig 1). Twenty-five μg For t 2 DNA was determined as the optimal dose after several dose-finding experiments (Fig S1, data not shown). For each treatment, the hair of the abdominal area of the mice was removed using a depilatory, tape-stripped, then patched with 25 μg For t 2 DNA vaccine for one hour and removed. A total of three treatments were given spaced one week apart (Fig 1 and Fig S2). For t 2 proteins were detected in the patched skin and the immune organ spleen at 24 hours and had significantly increased at 48 hours (Fig S3). Scratch bouts after rFor t 2 challenge were used as a clinical surrogate of itch. We measured total IgE and For t 2-specific IgG2a in the sera as well as mRNA and proteins of IL-13, interferon-gamma, IL-10, and FOXP3 in the culture supernatants of splenocytes after stimulation with various doses of rFor t 2 at 37℃ for 3-5 days by ELISA and real-time quantitative PCR. Histopathology of the challenged skins was examined.We found that after epicutaneous DNA vaccination, the allergen-induced itch of the mice significantly improved, and For t 2-specific IgG2a increased (Fig 2). Both mRNA and protein of IL-13, and eosinophils infiltration in the targeted skin, significantly decreased. Expression of FOXP3 mRNA increased (Fig S4-S6).This is the first study to demonstrate an epicutaneous anti-allergic DNA vaccine that is effective at both treating an established allergic condition and preventing the development of an allergic disease using biting midge allergy as a model. After epicutaneous DNA vaccination, in addition to the significant improvement in allergen-induced itch, the changes of biomarkers for allergic inflammation, including IgE, allergen-specific IgG2a, allergen-challenge-induced eosinophil infiltration in the skin, Th2 cytokines from the splenocytes, and regulatory T cell-related transcription factors, suggest that immune tolerance was induced after three patches of the epicutaneous DNA vaccine.Our data show that though the molecular weight of the For t 2 DNA vaccine is as high as 4000 base pairs, it is able to penetrate the dermal barrier and translates the corresponding protein in the targeted skin as well as the spleen of the vaccinated mice. It is possible that the DNA vaccine passes the epidermis via the hair follicles as the skin is tape-stripped before epicutaneous vaccination.6The mode of this anti-allergic epicutaneous DNA vaccine may have potential for use in other specific immunotherapies for other allergens.Mey Fann Lee1Chi Sheng Wu2 Shyh Jye Lin3Yi Hsing Chen2,4*1Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan2Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan3School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan4School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
Tuberculosis of the upper gastrointestinal tract is a rare pathology. Stomach tuberculosis, particularly, can appear as a subepithelial gastric tumor. We describe a case of a Patient with tuberculous intraperitoneal lymphadenitis mimicking the submucosal gastric tumor. An exploratory laparotomy was performed, and the diagnosis was confirmed by frozen section examination.
A rare autosomal recessive condition, Arterial tortuosity syndrome (ATS) presents with ectactic blood vessels, cutaneous laxity, and bowel rupture. We report a case of an asymptomatic infant with arterial tortuosity syndrome who presented with left ventricular hypertrophy without any obvious obstruction to the outflow tract.
Abstract Background: The aim of this study was to evaluate the potential effect of 6-minute walking distance (6MWD) on exercise tolerance in patients with pulmonary hypertension (PH). To clarify whether 6WMD and right ventricle (RV) function measured by three-dimensional echocardiography (3D-echo) could result in better correlation with exercise capacity. Methods: 72 consecutive patients underwent right heart catheterization (RHC) and diagnosed with PH. Associations between 6WMD and measures of RV function were evaluated using the Pearson correlation coefficient. Receiver operating characteristic (ROC) curve analysis was applied to evaluate the clinical prognosis of patients. Results: RHC-derived parameters were significantly correlated with 6MWD: (RPVR = -0.719, RPAPs = -0.501, RPAPd = -0.404, and RPAPm = -0.468, all P <0.001). Meanwhile, 6MWD was positively correlated with CO (R = 0.54, P <0.001). Good correlations between 6MWD with 3D-echo parameters were shown as follows: R3D-RVEDV = -0.584, R3D-RVESV = -0.598, R3D-RVEF = 0.554, R3D-RV mass = -0.507, all P <0.001. The predictive value from 6MWD was not much inferior to the predictive values of PVR (AUC6MWD = 0.779 vs. AUCPVR = 0.875, both P <0.0001). Conclusions: 6MWD has a significant correlation with hemodynamic parameters obtained by RHC. And RV function obtained by 3D-echo result in better correlation with exercise capacity. 3D-echo might be candidate for RHC to assess right heart function in patients with PH.
Light chain systemic amyloidosis has low clinical incidence rate and poor prognosis. Relevant diagnosis depends on the biopsy results, and many patients were not confirmed until autopsy. Once amyloidosis is suspected, it is necessary to communicate with their families on the risks for treatment methods and prognosis.
Aim- To describe the pattern of clinical presentation of patients with neurofibromatosis in a homogeneous black African population with emphasis on ophthalmological presentation in a multidisciplinary management setting. Methods- Ophthalmology clinic records from the Department of Ophthalmology and database of the Department of Pathology, both of University College Hopsital, Ibadan, Nigeria were reviewed for cases of neurofibromatosis over a 10-year period (Jan 2010 and Dec 2019). Relevant demographic, clinical information, management, complications and patient follow up were extracted from the records and entered into a spreadsheet and analysed. Results - The 34 cases included in this study comprised 19 males (55.9%) and age ranged from 18 months – 60 years, with a median age of 15 years. The male to female ratio was 1.3:1 with approximately 35.3% (12 patients) in the paediatric age group. The most frequent reason for consultation was unilateral progressive painless lid swelling (plexiform neurofibroma) often associated with ptosis. There was a positive family history of neurofibromatosis in 9 out of 32 cases (28.1%). Café au laît macules were observed in 22 out of 25 (88%) of cases. Typical neurofibromas were present in 84.8% of the patients. There was no significant difference in prevalence of plexiform neurofibromas with age (p= 0.05) or sex (p= 0.79). Bone and joint abnormalities was present in 17.6% of the patients. Ophthalmic examination showed conjunctiva changes in 3 cases, prominent cornea nerves in 2 cases. Iris lisch nodules was present in 75.9% of cases that had documentation, cataract in 2 cases and optic atrophy in 6cases.Three patients had ophthalmic pathway gliomas. Patients were managed by multidisciplinary teams depending on their needs. Conclusion- Multidisciplinary team management is advocated because of the multi-system disorders these patient have and the need for holistic, patient centred care that is of good quality, and sustainable.
Community ecology includes linking variation in system functions to the distribution and abundance of taxa. In inferring processes, functions, and causal taxa, it is common practice to assume a core community can be defined and that attributes of the core are representative of the entire dataset. Assuming categorical thresholds in abundance exist has the potential to be misleading, especially if rare taxa are contributing to ecological processes. Additionally, there are no standard criteria for core membership, complicating comparisons across studies. Rather, the existence of a core set of taxa can be treated as a hypothesis that may or may not be supported. We considered four methods commonly used for defining a core in studies of microbiomes and applied them to two published microbial data sets and simulations covering a range of plausible communities. We evaluated the ability of each method to correctly categorize taxa. Assignment of core taxa varied substantially among methods and datasets. Additionally, the ability of evaluated methods to capture the simulated core was contingent on the distribution of taxon abundances. While able to correctly identify core taxa in select cases, the methods disagreed more often than not. Given the lack of agreement among core assignment methods, categorization of taxa into sets corresponding to core and non-core is questionable and requires testing and validation before use in any particular context. Our results do not support applying methods of dimension reduction for core taxa classification, but instead provide additional rationale to favor analyses that use abundance data in their entirety.