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Multiplex signal cascade fluorescent biosensing for single nucleotide polymorphisms e...
Shenghui Li
Huan Yan

Shenghui Li

and 4 more

July 08, 2022
Glioma seriously endangers human lives and health, and precise SNPs genotyping is the key to modern clinical theranostics. A single nucleic acid signal amplification strategy cannot effectively ensure sensitivity and specificity detection. Herein, a multiplex signal amplification platform based on collaborative chain reaction (LCR, HCR) and cascaded rolling circle reaction (RCA) was first presented for specific and sensitive single nucleotide polymorphisms (SNPs) enhanced genotyping. The elongation HCR products were G-quadruplex and enriched on the magnetic nanoparticles (MBs). As the fluorescent intercalator, the thioflavin T (ThT) ligand was significantly embedded G-quadruplex structure for fluorescence enhancement, to indicate the mutation occurrence. Making use of the multiplex signal amplification strategy, as low as 1×10 -17 mol/L mutated strands can be detected, and the allele frequency determined was accurately achieved at 0.5%, indicating high sensitivity and high fidelity. Furthermore, this portable LCR-HCR-RCA multiplex signal cascade fluorescent biosensing (LHRCA) was combined with the efficient enrichment and rapid separation of magnetic nanoparticles (MBs), and suitable for glioma cell lysate samples analysis, making it a promising candidate for disease-associated SNPs discrimination.
Omega-3 polyunsaturated fatty acid-induced vasodilation in mouse aorta and mesenteric...
Cristiana Bercea
Roshan Limbu

Cristiana Bercea

and 8 more

July 08, 2022
There is strong evidence that the omega-3 polyunsaturated fatty acids (n-3 PUFAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have cardioprotective effects. n-3 PUFAs cause vasodilation in hypertensive patients, in part controlled by increased membrane conductance to potassium. As KATP play a major role in vascular tone regulation and are involved in hypertension, we aimed to verify whether n-3 PUFA-mediated vasodilation involved the opening of KATP channels. We used a murine model in which the KATP channel subunit, Kir6.1, is deleted in vascular smooth muscle. The vasomotor response of preconstricted arteries to physiologically relevant concentrations of DHA and EPA was measured using wire myography, using the channel blocker PNU-37883A. The effect of n-3 PUFAs on potassium currents in wild-type native smooth muscle cells was investigated using whole-cell patch clamping. DHA and EPA induced vasodilation in mouse aorta and mesenteric arteries; relaxations in the aorta were sensitive to KATP blockade with PNU-37883A. Endothelium removal didn’t affect relaxation to EPA and caused a small but significant inhibition of relaxation to DHA. In the knock-out model, relaxations to DHA and EPA were unaffected by channel knockdown but were still inhibited by PNU-37883A, indicating that the action of PNU-37883A on relaxation may not reflect inhibition of KATP. In native aortic smooth muscle cells DHA failed to activate KATP currents. We conclude that DHA and EPA cause vasodilation in mouse aorta and mesenteric arteries. Relaxations in blocker-treated arteries from knock-out mice demonstrate that KATP channels are not involved in the n-3 PUFA-induced relaxation.
A single serine in the CC3 region of STIM1 is critical for STIM1-Orai1 binding and CR...
Tao Yu
Xi Li

Tao Yu

and 6 more

July 08, 2022
Background and purpose: Store-operated Ca2+ entry (SOCE) is important for the function of many cell types. It is controlled by the interaction between ER Ca2+ sensor STIM1 and the plasma membrane Ca2+ channel Orai1. CAD of STIM1 is required for SOCE. It contains two putative coiled-coil regions (CC2 and CC3). The role of CC3 remains to be elucidated. Experimental approach: various plasmids carrying different fluorescent protein genes were constructed for better understanding the influence of S417G mutation in CC3 on SOCE activation; Confocal imaging system, calcium imaging technique and FRET technique were employed to examine the actions of 2-APB on the interaction between STIM1 C terminus and Orai1. Key results: Single-point mutation of the residue (S417G) abolishes STIM1 C-terminus interactions with Orai1. Mutation of S417 also abolished CAD-Orai1 binding and Orai1 channel activation, eliminated STIM1 puncta formation and co-localization with Orai1 and SOCE. 2-APB were found to restore the binding of STIM1 C-terminus mutant(S417G) to Orai1 and dose-dependently activated Orai1 channel. Both CBD and NBD of Orai1 is required for 2-APB-induced coupling between Orai1 and STIM1 C terminus mutant(S417G) and CRAC channel activation. We also demonstrated 2-APB lead to delayed activation of Orai1-K85E channel, although Orai1-K85E obviously impair 2-APB-induced STIM1 C-terminus mutant(S417G)-Orai1 coupling. Conclusions and implications: Our data suggest that S417 in the CC3 domain of STIM1 is critical for STIM1-Orai1 binding and CRAC channel activation. We also proposed experimental models of combined STM1 or Orai1 mutants with 2-APB to better understand the activation mechanism of CRAC.
Rational mutagenesis of Thermobifida fusca cutinase to modulate the enzymatic degrada...
Arpita Mrigwani
Madhav Pitaliya

Arpita Mrigwani

and 4 more

July 08, 2022
Thermobifida fusca cutinase ( TfC ) is a carboxylesterase (CE) that degrades the environmental pollutant, polyethylene terephthalate (PET). TfC also acts upon PET’s degradation intermediates (DIs), such as oligoethylene terephthalate (OET), and bis-/mono-hydroxyethyl terephthalate (BHET/MHET), to convert these into terephthalic acid (TPA), the terminal product of PET degradation. We examined TfC’s surface, compared it to that of other CEs, and performed molecular docking and MD simulations with an OET, 2HE-(MHET) 3, to understand interactions between TfC’s surface and the OET, at TfC’s active site as well as vicinal regions. We mutated 17 residues on TfC’s surface, mostly individually, but sometimes using pairs of mutations, to see how these modulate TfC’s activity. Most mutants/variants showed a decrease in activity against solid PET. Some killed activity completely. However, three mutations (L90F, F209I and F249R), made using a background mutation (G62A) already reported to improve activity by almost ~2.0-fold, yielded increases in activity that were between ~1.3- and ~2.0-fold higher than that of G62A TfC (which we found to display a ~1.7-fold increase in activity over TfC, in our own experiments). TfC variants, G62A/F249R, and G62A/F209I, exhibit the highest activities yet observed in any TfC mutants/variants, against PET, and BHET, respectively.
A closed, autologous bioprocess optimized for TCR-T cell therapies
Jennitte Stevens
Yijun Liu

Jennitte Stevens

and 10 more

July 08, 2022
Autologous cell therapy has proven to be an effective treatment for hematological malignancies. Cell therapies for solid tumors are on the horizon, however the high cost and complexity of manufacturing these therapies remain a challenge. Routinely used open steps to transfer cells and reagents through unit operations further burden the workflow reducing efficiency and increasing the chance for human error. Here we describe a fully closed, autologous bioprocess generating MAGE-B2 TCR-T cells. This bioprocess yielded 5 – 12e9 MAGE-B2-specific TCR-expressing T cells, transduced at low MOIs, within 7 to 10 days, and cells exhibited an enriched memory T cell phenotype and enhanced metabolic fitness. It was demonstrated that activating, transducing, and expanding leuko-apheresed cells in a single bioreactor without a T cell enrichment step promoted lentivirus transduction efficiency while resulting in comparable level of T cell purity (~97%) as that of leukopak cells that went through CD8+ and CD4+ positive selection. The critical process parameters of the bioreactor, including culturing at a high cell density (7e6 cells/mL), adjusting rocking agitations during phases of scale up, lowering glycolysis through addition of 2-Deoxy-D-glucose (2-DG), and modulating IL-2 levels, were shown to positively regulate TCR expression and cell doubling time, and promote resistance to effector-associated apoptosis of TCR-T cells. The bioprocess described herein supports scale-out feasibility by enabling processing of multiple patients’ batches in parallel within a Grade C cleanroom.
The Mini Electrode-equipped Catheter: Utility for Paroxysmal Supraventricular Tachyca...
Jin Iwasawa
Jacob Koruth

Jin Iwasawa

and 1 more

July 08, 2022
The Mini Electrode-equipped Catheter: Utility for Paroxysmal Supraventricular Tachycardia Ablation
Transaminase elevation during the first trimester and early pregnancy loss in patient...
Shuwen Zhang
Jiapo Li

Shuwen Zhang

and 4 more

July 08, 2022
Objective: To investigate the association between transaminase elevation during the first trimester and early pregnancy loss (EPL) in patients with recurrent spontaneous abortion (RSA). Further, the contributing risk factors for transaminase elevation in early pregnancy in RSA patients were analyzed Design: Cross-sectional study Setting: China Population: RSA patients during the first trimester Methods: Patients were divided into EPL group and N-EPL group as well as transaminase-elevated group (TE group) and transaminase-normal group (TN group). The relationship between transaminase level and EPL and the risk factors of elevated transaminase were investigated via student’s t test, Pearson chi-square test and logistic regression analyses. Main outcome measure: The association between transaminase elevation and EPL and the risk factors for elevated transaminase. Results: Higher serum transaminase levels were observed in EPL group than in the N-EPL group (p <0.05). Comparing with TN group, EPL is more common in TE group (p =0.018). There is still a correlation between elevated transaminases and EPL in RSA patients after adjusting for covariates (AST: OR, 1.018; 95% CI, 1.007-1.029; p, 0.001; ALT: OR, 1.006; 95%CI, 1.001-1.011; p, 0.018). The higher the transaminases, the greater the likelihood of EPL (p <0.05). Multivariate regression analysis found that the use of IVIG was an independent risk factor for elevated transaminase in RSA patients (OR, 0.374; 95% CI, 0.162-0.864; p =0.021). Conclusion: Serum transaminase levels are significantly correlated with RSA early pregnancy loss. Moreover, medication use is significantly correlated with transaminase elevation in the first trimester in RSA patients, especially IVIG.
Novel biallelic mutations in TMEM126B cause splicing defects and lead to Leigh syndro...
Ya Wang
Xiyue Zhou

Ya Wang

and 13 more

July 08, 2022
Leigh syndrome (LS) is one of the most common mitochondrial disease subtypes, caused by mutations in either the nuclear or mitochondrial genomes. TMEM126B was identified as a mitochondrial complex I assembly factor. Here, we identified a novel intronic mutation (c.82-2A>G) and a novel exonic insertion mutation (c.290dupT) in TMEM126B from a Chinese patient with clinical manifestations of LS. In silico predictions, minigene splicing assays and patients’ RNA analyses determined that the c.82-2A>G mutation resulted in complete exon 2 skipping, and the c.290dupT mutation provoked partial and complete exon 3 skipping, leading to translational frameshifts and premature termination. Functional analysis revealed the impaired mitochondrial function in patient-derived lymphocytes due to the complex I content and assembly defect. Although TMEM126B mutations have been related to multi-symptoms (exercise intolerance, severe muscle weakness, hyperlactic acidemia, pure myopathy, chronic renal failure and cardiomyopathy), we found the patient carrying these two mutations developed an middle-onset LS. Altogether, this is the first report that the patient carrying TMEM126B mutations was diagnosed with LS. Our data uncover the functional effect and the molecular mechanism of the pathogenic variants c.82-2A>G and c.290dupT, which expand gene mutation spectrum of LS and clinical spectrum caused by TMEM126B mutations.
Is low vitamin D status in pregnancy associated with adverse outcomes? :a prospective...
Jiaoyang Shi
Xiaoxin Yao

Jiaoyang Shi

and 7 more

July 08, 2022
Objectives: The relative contributions of vitamin D status to pregnancy complications are not fully understood. We investigated the correlation between vitamin D status and pregnancy outcomes. Design: Prospective analysis of cases Setting: China Population or Sample: A total of 1766 pregnant women admitted to The Eighth Affiliated Hospital, Sun Yat-sen University and Guangdong Women and Children Hospital between January 2019 and December 2020. Methods: This prospective cohort study was performed on women who paid antennal visits during their whole gestation. Serum 25-hydroxyvitamin D [25(OH)D] concentrations were measured among women before 24 weeks of gestation. Associations between maternal vitamin D status, maternal characteristics, and pregnancy outcomes were assessed. The adjusted odds ratio (OR) for adverse pregnancy outcomes was calculated using the logistic regression analysis. Results: Among all the participants ,192(10.87%), 1023(57.93%) and 551(31.20%) were defined as vitamin D sufficiency, insufficiency, and deficiency, respectively. There was no significant difference in vitamin D between pregnant women with adverse pregnancy outcomes and those without adverse pregnancy outcome. Neither vitamin D deficiency nor insufficiency was associated with adverse pregnancy outcomes compared with vitamin D sufficiency. Risks of adverse outcomes were as follows: GDM (OR=0.72 95%CI 0.46-1.14; OR=0.86 95%CI 0.57-1.30), SGA (OR=1.38 95%CI 0.73-2.60; OR=1.28 95%CI 0.70-2.34), early preterm delivery (OR=0.59 95%CI 0.13-2.70; OR=0.84 95%CI 0.23-3.00), PE (OR=3.44 95%CI 0.43-27.52; OR=2.40 95%CI 0.31-18.50), and postpartum hemorrhage (OR=0.58 95%CI 0.33-1.03; OR=0.81 95%CI 0.49-1.35). Conclusions: Low vitamin D status may not be associated with adverse pregnancy outcomes. Vitamin D screening in all pregnant women seems not reasonable.
Review of biomechanical deviations among nonpregnant, pregnant, and postpartum cohort...
Linjuan WEI
Yan WANG

Linjuan WEI

and 4 more

July 08, 2022
Objective: This review analyzed available studies on biomechanical changes during the pre-, in-, and post-pregnancy periods. Data sources: in the electronic databases of PubMed, Scopus, and Cochrane from inception until June 2, 2021 Study eligibility criteria: 1) the research object of the literature is healthy pregnant women; 2) the research direction is in the range of biomechanics, which can be related to the trunk, lumbar spine, hip joint, knee joint, ankle joint, wrist joint, foot, muscle strength, muscle endurance, joint strength, plantar pressure, and motion analysis; 3) with full text; 4) written in English or Chinese;and 5) cohort studies comparing pregnant women with the same group of women in the pre-pregnancy period or with nonpregnant women. Study appraisal and synthesis methods: Using National Institutes of Health quality assessment tool for observational cohort and cross-sectional studies to assessment the quality of the reviewed articles.Synthesized the general information(authors,publication years,country where the studies were conducted etc.),age of the studied subjects,investigated periods,sample size,objectives,study ammetersers,measurement tools,and outcomes of reviewed studies. Results: Duplicate results were removed,the search returned 2918 reports.Fourteen studies met the selection criteria. Conclusion: These studies revealed biomechanical deviations in body stability, motion patterns, and gait modes during these three periods. Regarding research content, there are insufficient studies on certain critical biomechanical aspects, such as the kinetic parameters of the inner body, which are the most direct factors related to musculoskeletal problems. According to quality assessment tool , a more comprehensive and explicit understanding of pregnancy biomechanics can be expected.
The meaning of life
Rui-Hong Xue

Rui-Hong Xue

July 08, 2022
The meaning of life
Analytical and Numerical Study of a Nonlinear Volterra Integro-differential Equation...
Mohamed Moumen Bekkouche
Abdelaziz Azeb Ahmed

Mohamed Moumen Bekkouche

and 4 more

July 08, 2022
In this paper we interest concerns an integro-differential equation of Volterra when the derivative of the solution appears under the sign of integration in a non-linear way. The derivation is the Caputo-Fabrizio Fractional Derivative (CF-FD), which increases the interest of this study. we built Lipchitz conditions to obtain the existence and uniqueness of the solution in a Banach space specific to the derivative of Caputo. The analytical study is followed by a complete numerical study.
Generalized Keratosis Pilaris induced by Testosterone Injections in Patient with CHAR...
fares alkhayal
Rima  Bin Fadliah

Fares Alkhayal

and 4 more

July 08, 2022
keratosis pilaris (KP) is an autosomal dominant disorder characterized by keratotic follicular papules with varying degrees of perifollicular erythema. Keratosis pilaris affects up to half of normal children and up to three-quarters of children with ichthyosis vulgaris. Most commonly it affects children with atopic eczema.
Optimization of adeno-associated virus (AAV) gene delivery into human bone marrow ste...
Shaomian Yao
Weiqiong  Rong

Shaomian Yao

and 3 more

July 08, 2022
Efficiently delivering nucleic acid into mammalian cells is essential to overexpress genes for assessing gene functions. Human bone marrow stem cells (hBMSCs) are the most studied tissue-derived stem cells. Adeno-associated viruses (AAVs) have been used to deliver DNA into hBMSCs for various purposes. This study optimized the AAV transduction protocol for high-efficiency DNA delivery into hBMSCs. hBMSCs were infected with different serotypes of AAVs containing green fluorescence (eGFP) reporter driven by the CMV promoter. GFP was monitored in the infected cells. Cells were collected at designated time points after the infection for RT-PCR to assess eGFP mRNA. The results indicated that the order of transduction efficiency of the AAV serotypes was AAV2 > AAV2.7 > AAV6 > AAV6.2 > AAV1 > AAD-DJ. AAV2 could achieve almost 100% transduction at the MOI greater than 100K. Over 90% of cells could be transduced at 20K to 50K MOI. About 80% transduction was seen at MOIs of 10K and 15K. The eGFP expression reached the maximum about15- 25 days post-AAV2 infection. High levels of transcription were still detectable at day 30 post-infection. We conclude that AAV2 and AAV2.7 can efficiently deliver transgene into hBMSCs for sustained expression over one month.
BUCCAL KAPOSI’S SARCOMA ASSOCIATED WITH HIV INFECTION AND COVID-19: A case report
Simon Carnot Ndrianarivony
Tahiriarivelo Randriamanantena

Simon Carnot Ndrianarivony

and 2 more

July 08, 2022
Kaposi's sarcoma is a common cancer associated with HIV infection. Since the COVID-19 pandemic, the prevalence of this pathology has increased. We report a case of a 33-year-old patient who presented with Kaposi's sarcoma associated with Covid-19 and HIV coinfection. It promotes the progression of cancers and increases mortality.
A monoterpene synthase regulates geraniol formation and plant defense via alternative...
Hao Jiang
Mengting Zhang

Hao Jiang

and 11 more

July 08, 2022
Geraniol is an important contributor to the pleasant floral scent of tea products and one of the most abundant aroma compounds in tea plants; however, its biosynthesis and physiological function in response to stress in tea plants remain unclear. Here, we studied eight terpene synthases with expression levels that were correlated with geraniol accumulation in different tissues of tea plants. The proteins encoded by the full-length terpene synthase ( CsTPS1) and its alternative splicing isoform ( CsTPS1- AS) could catalyze the formation of geraniol when GPP was used as a substrate in vitro, whereas the expression of CsTPS1- AS was only significantly induced by Colletotrichum gloeosporioides and Neopestalotiopsis sp. infection. Silencing of CsTPS1 and CsTPS1- AS resulted in a significant decrease in the geraniol content in tea plants. The geraniol content and antifungal activity of tea plants were compared when CsTPS1 and CsTPS1- AS were silenced. Down-regulation of the expression of CsTPS1- AS reduced the accumulation of geraniol, and the silenced tea plants exhibited greater susceptibility to pathogen infection than control plants. However, the geraniol content and pathogen resistance of CsTPS1-silenced plants and control plants did not significantly differ. Further analysis showed that silencing of CsTPS1- AS led to a decrease in the expression of the defense-related genes PR1 and PR2 and the expression of SA pathway-related genes in tea plants, which increased the susceptibility of tea plants to pathogenic fungal infections . Both in vitro and in vivo results indicated that CsTPS1 is involved in the regulation of geraniol formation and plant defense via alternative splicing in tea plants. The results of this study provide new insights into geraniol biosynthesis and highlight the role of monoterpene synthases in modulating plant disease resistance via alternative splicing.
PRACTICE OF L-ASPARAGINASE USAGE: A SURVEY AMONG HEALTHCARE PROVIDERS TREATING CHILDR...
Archana MV
Kalasekhar vijayasekharan

Archana MV

and 6 more

July 08, 2022
Introduction: L‑Asparaginase is an essential chemotherapeutic agent in the therapy of Acute Lymphoblastic Leukemia (ALL), which has led to improvement in survival. In low and middle-income countries like India, the outcomes in ALL are inferior compared to the published literature, one of the cause of which are believed to be due to the inferior quality of bioequivalent Asparaginase. The following survey attempts to understand the practice of using this agent among oncologists treating children with cancer in our country. Methods: The researchers designed a structured online questionnaire comprising 25 aspects of L-Asparaginase usage in the study. The questionnaire was directed to the healthcare providers involved in treating children with cancer in India. Results: Of the total 80 responses recorded, 51 (64%) respondents had more than five years of experience in pediatric oncology and were treating at least 5-10 newly diagnosed ALL patients per month. Forty-one (51%) respondents utilized Native Asparaginase, and 21 (26.3%) oncologists used PEGylated-Asparaginase exclusively. The most common route of administration was the intramuscular route (66.3%). Seventy percent of respondents utilized Native form at a dose of 10,000IU/m 2 and 20% at 6000IU/m 2. The amounts used for PEGylated L-Asparaginase were 1000IU/m 2, 2500IU/m 2, and variable doses in 48%, 40%, and 10% of responses, respectively. Though Serum Asparaginase assay (SAA) was not measured routinely in most of the centres, 39 (48.8%) healthcare providers perceived performing SAA helps to make the clinical decision. Conclusion: This survey shows a wide variation in L-Asparaginase usage among healthcare providers caring for children with cancer in our country. As L-Asparaginase is the pivotal component of ALL therapy, uniformity in its usage and dosing with the possibility of monitoring SAA due to the quality of bioequivalent may be one of the critical steps towards improving outcomes in ALL in our country.
Byzantine Failure against Colluding Attacks in Cloud Data
Noman Mazher

Noman Mazher

and 1 more

July 11, 2022
Cloud computing is the next stage in evolution of the internet, which provides large amounts of computing and storage to customers provisioned as a service over the internet. However, cloud computing faces so many security challenges due to the possible compromise or byzantine failures. In this paper, we focus on Ensuring data storage security in cloud computing, which is an important aspect of Quality of Service (QoS). We propose an effective and flexible distribution verification protocol to address data storage security in cloud computing. In this protocol, we rely on erasure code for the availability, reliability of data and utilize token precomputation using Sobol Sequence to verify the integrity of erasure coded data rather than Pseudorandom Data in existing systems. Unlike prior works, our scheme provides more security to user data stored in cloud computing. The performance analysis shows that our scheme is more secure than existing systems against Byzantine failure, unauthorized data modification attacks, and even cloud server colluding attacks.
Economic pressures of Covid-19 lockdowns result in increased timber extraction within...
Jacquelyn Tleimat
Sarah Fritts

Jacquelyn Tleimat

and 5 more

July 08, 2022
Although the COVID-19 lockdowns in 2020 had some environmental benefits, the pandemic’s impact on the global economy has also had conservation repercussions, especially in biodiverse nations. Ecuador, which is heavily reliant on petroleum, agricultural exports, and ecotourism, experienced a rise in poverty in response to pandemic shutdowns. In this study, we sought to quantify levels of illegal timber extraction and poaching before and after the start of COVID-19 lockdowns throughout two protected areas (Reserva Jama Coaque [JCR] and Reserva Bosque Seco Lalo Loor [BSLL]) in the endangered Pacific Forest of Ecuador. We analyzed chainsaw and gunshot acoustic data recorded from devices installed in the forest canopy from December 2019 to March 2020 and October 2020 to March 2021. Results from generalized linear mixed effects models indicated less chainsaw activity before lockdowns (post.lockdown = 0.571 + 0.196 SE, p-value = 0.004), although increased average rainfall also seemed to negatively affect chainsaw activity (avg.rainfall = -0.005 + 0.001 SE, p-value < 0.001). Gunshots were too infrequent to conduct statistical models; however, 87% of gunshots were detected during the ‘lockdown’ period. Observational data collected by rangers from these protected areas also noted an increase in poaching activities beginning mid to late 2020 and persisting into 2021. These results add to the steadily growing literature indicating an increase in environmental crime, particularly in biodiverse nations, catalyzed by COVID-19-related economic hardships. Identifying areas where environmental crime increased during pandemic lockdowns is vital to address both socioeconomic drivers and enforcement deficiencies to prevent further biodiversity loss and disease outbreaks and to promote ecosystem resilience. Our study also demonstrates the utility of passive acoustic monitoring to detect illegal resource extraction patterns, which can inform strategies such as game theory modeling for ranger patrol circuits and placement of real-time acoustic detection technologies to monitor and mitigate environmental crimes.
Viral infections and drug hypersensitivity
Charlotte Brüggen
Werner Pichler

Marie-Charlotte Brüggen

and 1 more

July 08, 2022
Virus infections and T cell-mediated drug hypersensitivity reactions (DHR) can influence each other. In most instances, systemic virus infections appear first. They may prime the reactivity to drugs in two ways: First, by virus-induced second signals: certain drugs like β-lactam antibiotics are haptens and covalently bind to various soluble and tissue proteins, thereby forming novel antigens. Under homeostatic conditions, these neo-antigens do not induce an immune reaction, probably because co-stimulation is missing. During a virus infection, the hapten-modified peptides are presented in an immune-stimulatory environment with co-stimulation. A drug-specific immune reaction may develop and manifest as exanthema. Second, by increased pharmacological interactions with immune receptors (p-i) : drugs tend to bind to proteins and may even bind to immune receptors. In the absence of viral infections, this low affine binding may be insufficient to elicit T cell activation. During a viral infection immune receptors are more abundantly expressed and allow more interactions to occur. This increases the overall avidity of p-i reactions and may even be sufficient for T cell activation and symptoms. There is a situation, where the virus-DHR sequence of events is inversed: in drug reaction with eosinophilia and systemic symptoms (DRESS), a severe DHR can precede reactivation and viremia of various herpes viruses. One could explain this phenomenon by the massive p-i mediated immune stimulation during acute DRESS, which coincidentally acvitates many herpes virus-specific T cells. Through p-i stimulation, they develop a cytotoxic activity with killing of herpes peptide-expressing cells and release of herpes viruses. These concepts could explain the often transient nature of DHR occurring during viral infections and the often asymptomatic herpes-virus viraemia after DRESS.
Drivers of population divergence and genetic variation in Elymus breviaristatus (Keng...
Jin Li
shiyong chen

Jin Li

and 5 more

July 08, 2022
Elymus breviaristatus (family Triticeae), a rare grass species with excellent resistance and ecological importance, is narrowly distributed on the Qinghai-Tibet Plateau (QTP). Populations of E. breviaristatus are declining due to habitat fragmentation, and thus far, characteristics of genetic differentiation and adaptive responses to climate change remain poorly understood in this species. Here, we explored the genetic structure of 18 natural populations (269 individuals) in the transition zone between Tibet and the Hengduan Mountains using 15 expressed sequence tag (EST)-SSR primer pairs and identified possible barriers to gene flow that might have caused genetic discontinuities. Additional analyses were performed to identify the environmental factors affecting genetic diversity and to test whether the patterns of genetic variation among populations were more consistent with the isolation by distance (IBD) or isolation by environment (IBE) model. Multiple measures of genetic diversity revealed that intra-population genetic variation was low, while inter-population genetic variation was high. Clustering, structure, and principal coordinate analyses identified three genetic groups: (a) Eastern Qamdo, (b) Nagqu and Western Qamdo, and (c) Lhasa and Nyingchi. A clear physical barrier to gene flow was formed by the Yarlung Zangbo Grand Canyon and the Tanggula Mountains. We found that both IBD and IBE contributed to the observed patterns of genetic variation, indicating that the process of population differentiation was affected by complex mechanisms. In addition, four precipitation-related variables significantly affected population genetic variation, especially in extremely cold and dry habitats. Overall, our results emphasized the genetic fragility of E. breviaristatus populations and showed that this species requires attention, as future climate changes and human activities may further threaten its survival. In addition, the genetic differences among E. breviaristatus populations should be considered when formulating conservation measures for E. breviaristatus populations in the study area.
Cost-efficient population genomic investigation of Daphnia longispina complex resting...
Jana Nickel
Mathilde Cordellier

Jana Nickel

and 1 more

July 08, 2022
Resting stages of aquatic organisms that accumulate in the sediment over time are an exceptional resource that allows direct insights into past populations and addressing evolutionary questions. This is of particular interest in taxa that have recently faced environmental changes such as the Daphnia longispina species complex, a keystone zooplankton group in European freshwater ecosystems. However, genomic analysis might be challenging as many of these resting stages are very small and the DNA might be degraded. To reliably allow the resequencing of single Daphnia resting eggs from different sediment layers and characterize genomic changes through time, we performed whole genome amplification to obtain DNA amounts suitable for genome re-sequencing and tested multiple protocols involving egg isolation, whole genome amplification kits and library preparation. A pre-sequencing contamination screening was developed to quickly assess possible contamination. In total, we successfully amplified and sequenced nine genomes from Daphnia resting eggs that could be identified as Daphnia longispina species. We analyzed the genome coverage and SNP calling of these samples to optimize this method for future projects involving population genomic investigation of the resting egg bank.
Phase-field modeling of near-neutral pH stress corrosion crack initiation life in und...
Edel R. Martinez
Solomon Tesfamariam

Edel R. Martnez

and 1 more

July 07, 2022
A unified phase-field theory is introduced to describe crack initiation and early crack growth due to pitting corrosion of pipelines in contact with near-neutral pH groundwater. The model incorporates a formulation that accounts for stochastic corrosion-induced crack nucleation events at pit sites. This approach supplies a modeling framework to handle the combined effects of electrochemical transformation of the original metal, hydrogen diffusion and resulting embrittlement of the original metal, and mechanical stresses. This is a robust computational approach to tracking the evolving metalelectrolyte interface and embrittlement regions. It was confirmed that dissolved hydrogen into the material promotes crack initiation over a wide potential range and that pitting corrosion, as a precursor of stress corrosion cracking, has a recognizable influence on strength over time. It is expected that this work provides the ground for modeling the pit-to-crack transition required to effectively control very slow crack-in-colonies in pipelines.
Leadless pacemaker implantation in dextrocardia with situs viscerum inversus: a case...
Luca Bontempi
Angelica Fundaliotis

Luca Bontempi

and 8 more

July 07, 2022
Leadless pacemaker implantation (LPI) has fewer device complications and reduced chance of infection compared to conventional pacemakers. Dextrocardia with situs viscerum inversus (DC+SVI) is a rare condition, which seldom leads to cardiac complications. However, its presence poses a challenge to operators in cardiac procedures. LPI reports in DC patients are scarce. We report a case of LPI in a DC+SVI patient, followed by a brief but comprehensive literature review.
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