Macrofauna community of the cold seep area at Site F, South China Sea

A cold seep is one of the typical deep-sea chemical energy ecosystems and a hotspot for studying unique life processes and biogeochemical cycles in the deep sea. Macrofauna, which is one of the most important components of the cold seep ecosystem, has not been thoroughly studied. We examined the macrofauna community at Site F using images collected in 2016 by an imaging and laser profiling system and biological samples collected in 2020 and 2021 by TV grab and a remotely operated vehicle. In total, 41 species were found. The overall number of macrofauna identified at Site F (20,000 m2) reached 252,943 individuals, and the biomass reached 726.15 kg by dry weight. As the dominant species, Gigantidas platifrons and Shinkaia crosnieri reached their highest densities of 629 and 396 individuals/m2, respectively. The comparisons between different stations revealed that the diversity and density, even the biomass of dominant species, were much higher in the south than in the north at Site F in 2020. Correlation analysis showed that methane had a positive effect on macrofauna density. Compared with S. crosnieri, G. platifrons seems to be more adapted to the harsh cold seep environment. Methane consumption rates of the dominant species show that macrofauna are important in influencing seafloor methane fluxes. Our findings provide valuable insights into the ecology, community structure, and biota-environment interaction in the cold seep at Site F

Deciphering the metabolic perturbation in hepatic alveolar echinococcosis: a 1 H NMR-based metabolomics study

Background: Hepatic alveolar echinococcosis (HAE) is caused by the growth of Echinococcus multilocularis larvae in the liver. It is a chronic and potentially lethal parasitic disease. Early stage diagnosis for this disease is currently not available due to its long asymptomatic incubation period. In this study, a proton nuclear magnetic resonance (1H NMR)-based metabolomics approach was applied in conjunction with multivariate statistical analysis to investigate the altered metabolic profiles in blood serum and urine samples obtained from HAE patients. The aim of the study was to identify the metabolic signatures associated with HAE. Results: A total of 21 distinct metabolic differences between HAE patients and healthy individuals were identified, and they are associated with perturbations in amino acid metabolism, energy metabolism, glyoxylate and dicarboxylate metabolism. Furthermore, the present results showed that the Fischer ratio, which is the molar ratio of branched-chain amino acids to aromatic amino acids, was significantly lower (P < 0.001) in the blood serum obtained from the HAE patients than it was in the healthy patient group. Conclusions: The altered Fischer ratio, together with perturbations in metabolic pathways identified in the present study, may provide new insights into the mechanistic understanding of HAE pathogenesis and potential therapeutic interventions

Ultrafast neuronal imaging of dopamine dynamics with designed genetically encoded sensors

Neuromodulatory systems exert profound influences on brain function. Understanding how these systems modify the operating mode of target circuits requires measuring spatiotemporally precise neuromodulator release. We developed dLight1, an intensity-based genetically encoded dopamine indicator, to enable optical recording of dopamine dynamics with high spatiotemporal resolution in behaving mice. We demonstrated the utility of dLight1 by imaging dopamine dynamics simultaneously with pharmacological manipulation, electrophysiological or optogenetic stimulation, and calcium imaging of local neuronal activity. dLight1 enabled chronic tracking of learning-induced changes in millisecond dopamine transients in striatum. Further, we used dLight1 to image spatially distinct, functionally heterogeneous dopamine transients relevant to learning and motor control in cortex. We also validated our sensor design platform for developing norepinephrine, serotonin, melatonin, and opioid neuropeptide indicators

Area Disease Estimation Based on Sentinel Hospital Records

BACKGROUND: Population health attributes (such as disease incidence and prevalence) are often estimated using sentinel hospital records, which are subject to multiple sources of uncertainty. When applied to these health attributes, commonly used biased estimation techniques can lead to false conclusions and ineffective disease intervention and control. Although some estimators can account for measurement error (in the form of white noise, usually after de-trending), most mainstream health statistics techniques cannot generate unbiased and minimum error variance estimates when the available data are biased. METHODS AND FINDINGS: A new technique, called the Biased Sample Hospital-based Area Disease Estimation (B-SHADE), is introduced that generates space-time population disease estimates using biased hospital records. The effectiveness of the technique is empirically evaluated in terms of hospital records of disease incidence (for hand-foot-mouth disease and fever syndrome cases) in Shanghai (China) during a two-year period. The B-SHADE technique uses a weighted summation of sentinel hospital records to derive unbiased and minimum error variance estimates of area incidence. The calculation of these weights is the outcome of a process that combines: the available space-time information; a rigorous assessment of both, the horizontal relationships between hospital records and the vertical links between each hospital's records and the overall disease situation in the region. In this way, the representativeness of the sentinel hospital records was improved, the possible biases of these records were corrected, and the generated area incidence estimates were best linear unbiased estimates (BLUE). Using the same hospital records, the performance of the B-SHADE technique was compared against two mainstream estimators. CONCLUSIONS: The B-SHADE technique involves a hospital network-based model that blends the optimal estimation features of the Block Kriging method and the sample bias correction efficiency of the ratio estimator method. In this way, B-SHADE can overcome the limitations of both methods: Block Kriging's inadequacy concerning the correction of sample bias and spatial clustering; and the ratio estimator's limitation as regards error minimization. The generality of the B-SHADE technique is further demonstrated by the fact that it reduces to Block Kriging in the case of unbiased samples; to ratio estimator if there is no correlation between hospitals; and to simple statistic if the hospital records are neither biased nor space-time correlated. In addition to the theoretical advantages of the B-SHADE technique over the two other methods above, two real world case studies (hand-foot-mouth disease and fever syndrome cases) demonstrated its empirical superiority, as well

Ultrafast neuronal imaging of dopamine dynamics with designed genetically encoded sensors

Neuromodulatory systems exert profound influences on brain function. Understanding how these systems modify the operating mode of target circuits requires measuring spatiotemporally precise neuromodulator release. We developed dLight1, an intensity-based genetically encoded dopamine indicator, to enable optical recording of dopamine dynamics with high spatiotemporal resolution in behaving mice. We demonstrated the utility of dLight1 by imaging dopamine dynamics simultaneously with pharmacological manipulation, electrophysiological or optogenetic stimulation, and calcium imaging of local neuronal activity. dLight1 enabled chronic tracking of learning-induced changes in millisecond dopamine transients in striatum. Further, we used dLight1 to image spatially distinct, functionally heterogeneous dopamine transients relevant to learning and motor control in cortex. We also validated our sensor design platform for developing norepinephrine, serotonin, melatonin, and opioid neuropeptide indicators

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

The complete mitochondrial genome of Asteroschema tubiferum (Ophiuroidea: Euryalida: Asteroschematidae)

We describe the first mitochondrial genome of a brittle star Asteroschema tubiferum Matsumoto 1911 in family Asteroschematidae. The mitogenome was sequenced and assembled using next-generation sequencing technology, and were 16,361 bp in size with 37 genes containing 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and a control region. The phylogenetic tree was constructed based on 13 protein-coding mitochondrial genes of A. tubiferum and 26 species in the phylum Echinodermata by RAxML, which showed that it was mostly related to the species in Family Gorgonocephalidae. These results could provide a novel insight to the phylogeny of Ophiuroidea

Kyphoscoliosis with Klippel-Trenaunay syndrome: a case report and literature review

Abstract Background Klippel-Trenaunay syndrome (KTS) is a rare congenital syndrome characterized by the triad of venous varicosities, capillary malformations and limb hypertrophy. However, KTS may rarely occur in combination with kyphoscoliosis. Case presentation We presented an 18-year-old female with KTS and kyphoscoliosis. Hypertrophy of bone and soft tissue affected her left face, trunk and lower limb. Moreover, the patient is associated with subacute thyroiditis, vitamin D deficiency and iron deficiency anemia, high level of D-dimer, swollen tonsil, kyphoscoliosis and Chiari-I-malformation without syringomyelia. A posterior correction and spinal fusion from T10 to L5 levels were performed for this patient. The lumbar curve was corrected from 105° to 60° and the kyphosis improved from 58° to 26°. The distance of trunk shift decreased from 10 cm to 1.4 cm. There were no thrombotic events occurred. At the 8th month follow-up, there was no significantly change of the curve in the coronal and sagittal radiographs. During the 31-month follow-up, the patient did not experience any discomfort. And her general appearance did not have any change until the last follow-up. However, she refused to take radiograph for worrying about radiation. Conclusions KTS is a rare disease with classic clinical triad. However, it can also have other different features, including kyphoscoliosis, elevated D-Dimer, vitamin D deficiency and iron-deficiency anemia. These issues should be taken into consideration when planning treatment for kyphoscoliosis in KTS patients