The Influence of Body Size and Hemoglobin Multiplicity on Critical Oxygen Threshold in Red Drum (Sciaenops ocellatus)

Hypoxia is common in marine environments and fishes use a suite of cardiorespiratory adjustments to defend aerobic metabolism, including reducing standard metabolic rate (SMR), the minimum metabolic rate needed to sustain life at a specified temperature, or increasing hemoglobin (Hb)-O2 affinity. Nonetheless, hypoxia can constrain oxygen transport whereby fish cannot accommodate standard metabolic rate; a point known as critical oxygen tension (Pcrit). Currently, it is unclear how life history traits may impact Pcrit, but available data on red drum (Sciaenops ocellatus) suggest that its SMR decreases with size, and its transcriptome contains multiple Hb-α and Hb-β subunits. Therefore we sought to explore the influence of body size and acclimation to hypoxia. Critical oxygen tension (Pcrit) was measured for fish over a 2500-fold range in mass (0.26 - 686 g) and surprisingly showed an increase (Pcrit = 3.15 logM + 16.19; R2 = 0.44) despite decreasing SMR. Two groups of S. ocellatus (90.96 ± 5.00 g ranging from 69.7 g to 141.9 g) were also subjected to either normoxia ( > 95% P_(O_2 )) or hypoxia (30%±5% P_(O_2 )) treatment for two weeks. Only fish subjected to hypoxia treatment showed a statistically significant decrease in Pcrit after the treatment. Acclimation had no impact on gill surface area, diffusion distance or relative ventricular mass, but mRNA expression levels of the major Hb-α subunit switched from Hbα-3.1 in the normoxia group to Hbα-3.2 in the hypoxia treatment group and expression levels of Hbα-2, Hbα-3.2 and Hbβ-3.1 showed a statistically significant increase in the hypoxia treatment group. Decrease in P50 and thus an increase in Hb-O2 binding affinity was observed for fish subjected to hypoxia treatment. Taken together these data indicate that hypoxia tolerance is affected by both developmental stage and hypoxia acclimation.Integrative Biolog

A Coefficient-Embedding Ideal Lattice can be Embedded into Infinitely Many Polynomial Rings

Many lattice-based crypstosystems employ ideal lattices for high efficiency. However, the additional algebraic structure of ideal lattices usually makes us worry about the security, and it is widely believed that the algebraic structure will help us solve the hard problems in ideal lattices more efficiently. In this paper, we study the additional algebraic structure of ideal lattices further and find that a given ideal lattice in some fixed polynomial ring can be embedded as an ideal in infinitely many different polynomial rings. We explicitly present all these polynomial rings for any given ideal lattice. The interesting phenomenon tells us that a single ideal lattice may have more abundant algebraic structures than we imagine, which will impact the security of corresponding crypstosystems. For example, it increases the difficulties to evaluate the security of crypstosystems based on ideal lattices, since it seems that we need consider all the polynomial rings that the given ideal lattices can be embedded into if we believe that the algebraic structure will contribute to solve the corresponding hard problem. It also inspires us a new method to solve the ideal lattice problems by embedding the given ideal lattice into another well-studied polynomial ring. As a by-product, we also introduce an efficient algorithm to identify if a given lattice is an ideal lattice or not

Soliton Molecules and Multisoliton States in Ultrafast Fibre Lasers: Intrinsic Complexes in Dissipative Systems

Benefiting from ultrafast temporal resolution, broadband spectral bandwidth, as well as high peak power, passively mode-locked fibre lasers have attracted growing interest and exhibited great potential from fundamental sciences to industrial and military applications. As a nonlinear system containing complex interactions from gain, loss, nonlinearity, dispersion, etc., ultrafast fibre lasers deliver not only conventional single soliton but also soliton bunching with different types. In analogy to molecules consisting of several atoms in chemistry, soliton molecules (in other words, bound solitons) in fibre lasers are of vital importance for in-depth understanding of the nonlinear interaction mechanism and further exploration for high-capacity fibre-optic communications. In this Review, we summarize the state-of-the-art advances on soliton molecules in ultrafast fibre lasers. A variety of soliton molecules with different numbers of soliton, phase-differences and pulse separations were experimentally observed owing to the flexibility of parameters such as mode-locking techniques and dispersion control. Numerical simulations clearly unravel how different nonlinear interactions contribute to formation of soliton molecules. Analysis of the stability and the underlying physical mechanisms of bound solitons bring important insights to this field. For a complete view of nonlinear optical phenomena in fibre lasers, other dissipative states such as vibrating soliton pairs, soliton rains, rogue waves and coexisting dissipative solitons are also discussed. With development of advanced real-time detection techniques, the internal motion of different pulsing states is anticipated to be characterized, rendering fibre lasers a versatile platform for nonlinear complex dynamics and various practical applications

Soliton Molecules and Multisoliton States in Ultrafast Fibre Lasers: Intrinsic Complexes in Dissipative Systems

Benefiting from ultrafast temporal resolution, broadband spectral bandwidth, as well as high peak power, passively mode-locked fibre lasers have attracted growing interest and exhibited great potential from fundamental sciences to industrial and military applications. As a nonlinear system containing complex interactions from gain, loss, nonlinearity, dispersion, etc., ultrafast fibre lasers deliver not only conventional single soliton but also soliton bunching with different types. In analogy to molecules consisting of several atoms in chemistry, soliton molecules (in other words, bound solitons) in fibre lasers are of vital importance for in-depth understanding of the nonlinear interaction mechanism and further exploration for high-capacity fibre-optic communications. In this Review, we summarize the state-of-the-art advances on soliton molecules in ultrafast fibre lasers. A variety of soliton molecules with different numbers of soliton, phase-differences and pulse separations were experimentally observed owing to the flexibility of parameters such as mode-locking techniques and dispersion control. Numerical simulations clearly unravel how different nonlinear interactions contribute to formation of soliton molecules. Analysis of the stability and the underlying physical mechanisms of bound solitons bring important insights to this field. For a complete view of nonlinear optical phenomena in fibre lasers, other dissipative states such as vibrating soliton pairs, soliton rains, rogue waves and coexisting dissipative solitons are also discussed. With development of advanced real-time detection techniques, the internal motion of different pulsing states is anticipated to be characterized, rendering fibre lasers a versatile platform for nonlinear complex dynamics and various practical applications

Long-term use of antibiotics and risk of type 2 diabetes in women:a prospective cohort study

BACKGROUND: Accumulating evidence suggested that long-term antibiotic use may alter the gut microbiome, which has, in turn, been linked to type 2 diabetes. We undertook this study to investigate whether antibiotic use was associated with increased risk of type 2 diabetes. METHODS: This prospective cohort study included women free of diabetes, cardiovascular disease and cancer in the Nurses’ Health Study (NHS 2008–2014) and NHS II (2009–2017). We evaluated the overall duration of antibiotics use in the past 4 years and subsequent diabetes risk with Cox proportional-hazards regression adjusting for demography, family history of diabetes and lifestyle factors. RESULTS: Pooled analyses of NHS and NHS II (2837 cases, 703 934 person-years) revealed that a longer duration of antibiotic use in the past 4 years was associated with higher risk of diabetes [Trend-coefficient = 0.09, 95% confidence interval (CI) 0.04 to 0.13]. Participants who received antibiotics treatment for a medium duration of 15 days to 2 months [hazard ratio (HR) 1.23, 95% CI 1.10 to 1.39] or long duration of >2 months (HR 1.20, 95% CI 1.02 to 1.38) had higher risk of type 2 diabetes as compared with non-users. Subgroup analyses suggested that the associations were unlikely to be modified by age, family history of diabetes, obesity, smoking, alcohol drinking, physical activity and overall diet quality. CONCLUSIONS: A longer duration of antibiotic use in recent years was associated with increased risk of type 2 diabetes in women. Physicians should exercise caution when prescribing antibiotics, particularly for long-term use

Structural and Lipidomic Alterations of Striatal Myelin in 16p11.2 Deletion Mouse Model of Autism Spectrum Disorder

Myelin abnormalities have been observed in autism spectrum disorder (ASD). In this study, we seek to discover myelin-related changes in the striatum, a key brain region responsible for core ASD features, using the 16p11.2 deletion (16p11.2±) mouse model of ASD. We found downregulated expression of multiple myelin genes and decreased myelin thickness in the striatum of 16p11.2± mice versus wild type controls. Moreover, given that myelin is the main reservoir of brain lipids and that increasing evidence has linked dysregulation of lipid metabolism to ASD, we performed lipidomic analysis and discovered decreased levels of certain species of sphingomyelin, hexosyl ceramide and their common precursor, ceramide, in 16p11.2± striatum, all of which are major myelin components. We further identified lack of ceramide synthase 2 as the possible reason behind the decrease in these lipid species. Taken together, our data suggest a role for myelin and myelin lipids in ASD development

An FBXW7-ZEB2 axis links EMT and tumour microenvironment to promote colorectal cancer stem cells and chemoresistance

Colorectal cancer (CRC) patients develop recurrence after chemotherapy owing to the survival of stem cell-like cells referred to as cancer stem-like cells (CSCs). The origin of CSCs is linked to the epithelial–mesenchymal transition (EMT) process. Currently, it remains poorly understood how EMT programmes enable CSCs residing in the tumour microenvironment to escape the effects of chemotherapy. This study identifies a key molecular pathway that is responsible for the formation of drug-resistant CSC populations. Using a modified yeast-2-hybrid system and 2D gel-based proteomics methods, we show that the E3-ubiquitin ligase FBXW7 directly binds and degrades the EMT-inducing transcription factor ZEB2 in a phosphorylation-dependent manner. Loss of FBXW7 induces an EMT that can be effectively reversed by knockdown of ZEB2. The FBXW7-ZEB2 axis regulates such important cancer cell features, as stemness/dedifferentiation, chemoresistance and cell migration in vitro, ex vivo and in animal models of metastasis. High expression of ZEB2 in cancer tissues defines the reduced ZEB2 expression in the cancer-associated stroma in patients and in murine intestinal organoids, demonstrating a tumour-stromal crosstalk that modulates a niche and EMT activation. Our study thus uncovers a new molecular mechanism, by which the CRC cells display differences in resistance to chemotherapy and metastatic potential

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Role of synemin in astrocytoma cellmigration

Synemin is an intermediate filament (IF) protein with the unique property to incorporate into IF networks while also binding to actin-associated proteins such as a-actinin, vinculin, zyxin, and a-dystrobrevin. Interestingly, synemin is present in astrocytomas of all grades but not in normal, mature astrocytes. Synemin contribution to the malignant behavior of astrocytoma cells was explored through RNAi experiments that established that synemin is a positive regulator of astrocytoma cell motility. In support of this role is the abundance of synemin in cytoplasmic domains important for motility, such as leading edges and lamellipodias. Synemin down-regulation also disrupted actin organization and increased the proportion of unpolymerized actin. In addition, antagonizing synemin decreased the proportion of a-actinin associated with actin filaments, providing evidence that synemin interaction with a-actinin may influence actin dynamics upon which motility ultimately depends. In addition to synemin, astrocytoma cells express two other IF proteins, vimentin and nestin. These latter two proteins contribute to the motility of carcinoma and/or fibroblastic cells, raising the possibility that they function similarly in astrocytoma cells. However, in contrast to synemin, vimentin and nestin are not present in the leading edge of astrocytoma cells, suggesting that they influence motility through mechanism(s) distinct from that of synemin. Thus, antagonizing synemin function appears to diminish the motility of astrocytoma cells and future studies will determine whether antagonizing synemin can be accomplished with small molecules such as those being developed to target other IF proteins

Could histamine h1 receptor antagonists be used for treating covid-19?

COVID-19 has rapidly become a pandemic worldwide, causing extensive and long-term health issues. There is an urgent need to identify therapies that limit SARS-CoV-2 infection and improve the outcome of COVID-19 patients. Unbalanced lung inflammation is a common feature in severe COVID-19 patients; therefore, reducing lung inflammation can undoubtedly benefit the clinical manifestations. Histamine H1 receptor (H1 receptor) antagonists are widely prescribed medications to treat allergic diseases, while recently it has emerged that they show significant promise as anti-SARS-CoV-2 agents. Here, we briefly summarize the novel use of H1 receptor antagonists in combating SARS-CoV-2 infection. We also describe the potential antiviral mechanisms of H1 receptor antagonists on SARS-CoV-2. Finally, the opportunities and challenges of the use of H1 receptor antagonists in managing COVID-19 are discussed.</p