bluuebunny/crossref_metadata_2025 huggingface dataset:
The Importance of the Orbital Parameters for the Indian Summer Monsoon During the Mid-Holocene, as Deciphered From Atmospheric Model Experiments
Authors: Tejavath Charan Teja , Ashok Karumuri , Chakraborty Supriyo
Published: May 2021

Proxy and model-based studies suggest multi-scale temporal variability in the Indian summer monsoon (ISM). In this study, using the CESM1 atmospheric general circulation model, we carried out multiple ensemble AGCM simulations for the Mid-Holocene (MH; ≈ 6 kyr BP), Medieval Warm Period (MWP; ≈ 1 kyr BP), Little Ice Age (LIA; ≈ 0.35 kyr BP), and Historical (HS; ≈ CE 2000) periods. We used the PMIP3/CMIP5 boundary conditions for this purpose. Our simulations indicate that the ISM during the MH was stronger compared to HS and the rainfall higher, in agreement with several proxy studies. The experiments also suggest that the ISM rainfall (ISMR) was higher during MWP relative to the LIA in agreement with our earlier results from the PMIP3 models. A relatively northward migration of the ITCZ over the Indian region and strengthening of the neighboring subtropical high over the northwestern Pacific, both associated with stronger insolation associated with the obliquity and precision during the MH, seem to be important reason Indian summer monsoon during the MH.
How Does the Arctic Sea Ice Affect the Interannual Variability of Tropical Cyclone Activity Over the Western North Pacific?
Authors: Fu Hao , Zhan Ruifen , Wu Zhiwei , Wang Yuqing , Zhao Jiuwei
Published: May 2021

Although many studies have revealed that Arctic sea ice may impose a great impact on the global climate system, including the tropical cyclone (TC) genesis frequency over the western North Pacific (WNP), it is unknown whether the Arctic sea ice could have any significant effects on other aspects of TCs; and if so, what are the involved physical mechanisms. This study investigates the impact of spring (April-May) sea ice concentration (SIC) in the Bering Sea on interannual variability of TC activity in terms of the accumulated cyclone energy (ACE) over the WNP in the TC season (June-September) during 1981–2018. A statistical analysis indicates that the spring SIC in the Bering Sea is negatively correlated with the TC season ACE over the WNP. Further analyses demonstrate that the reduction of the spring SIC can lead to the westward shift and intensification of the Aleutian low, which strengthens the southward cold-air intrusion, increases low clouds, and reduces surface shortwave radiation flux, leading to cold sea surface temperature (SST) anomaly in the Japan Sea and its adjacent regions. This local cloud-radiation-SST feedback induces the persistent increasing cooling in SST (and also the atmosphere above) in the Japan Sea through the TC season. This leads to a strengthening and southward shift of the subtropical westerly jet (SWJ) over the East Asia, followed by an anomalous upper-level anticyclone, low-level cyclonic circulation anomalies, increased convective available potential energy, and reduced vertical wind shear over the tropical WNP. These all are favorable for the increased ACE over the WNP. The opposite is true for the excessive spring SIC. The finding not only has an important implication for seasonal TC forecasts but also suggests a strengthened future TC activity potentially resulting from the rapid decline of Arctic sea ice.
Correlation of Osteoporosis in Patients With Newly Diagnosed Type 2 Diabetes: A Retrospective Study in Chinese Population
Authors: Wen Yuhua , Li Huijuan , Zhang Xiaoya , Liu Peipei , Ma Jing , Zhang Liya , Zhang Keqin , Song Lige
Published: May 2021

This study aimed to explore the risk factors attributed to osteoporosis in newly type 2 diabetes mellitus (T2DM) patients. This study aimed to recruit 244 T2DM patients and 218 non-diabetic controls. We collected demographic characteristics, medical history, bone mineral density and biomarkers including bone specific alkaline phosphatase (BALP), osteocalcin, N-terminal peptide of type I procollagen (P1NP), tartrate-resistant acid phosphatase 5b (TRCAP-5b), β-Cross Laps of type I collagen-containing cross-linked C-telopeptide (β-CTX), 25-hydroxyvitamin D, parathyroid hormone were recorded or detected. Bone mineral density (BMD) was our primary outcome. Based on the result of BMD, we divided both the control group and T2DM group into three subgroups: normal bone mass, osteopenia and osteoporosis. In control group, we found age, sex, menopausal status, BMI, P1NP, BALP, TRACP-5b, osteocalcin, and corrected serum calcium are differential among three subgroups. In T2DM group, we found age, sex, menopausal status, drinking status, BMI, HbA1c, TRACP-5b and OC were differential among three subgroups. In T2DM and control groups, age, female, postmenopausal status, BALP, TRACP-5b and osteocalcin were positively correlated while BMI was negatively correlated with osteoporosis. In control group, β-CTX was positively correlated with osteoporosis. In T2DM group, HbA1c and corrected serum calcium concentration were positively correlated with osteoporosis. After further adjustment of age, BMI in male, TRACP-5b was positively correlated with the risk of osteoporosis in newly diagnosed T2DM. After adjusted of age, BMI and menopausal status in female, OC was positively correlated with the risk of osteoporosis in newly diagnosed T2DM and controls. In female T2DM, BALP and P1NP were positively correlated with the risk of osteoporosis. In conclusion, age, BMI and menopausal status are common risk factors for osteoporosis in diabetic and non-diabetic patients, however TRACP-5b, BALP and osteocalcin are special risk factors for osteoporosis in newly diagnosed T2DM patients but not non-diabetic patients, which may be applied to identify osteoporosis risk in T2DM patients, but this result needs to be proven with fracture data.
Telomere Length Differently Associated to Obesity and Hyperandrogenism in Women With Polycystic Ovary Syndrome
Authors: Velazquez Mariela Edith , Millan Andrea L. , Rojo Mailén , Abruzzese Giselle Adriana , Cocucci Silvina Ema , Iglesias Molli Andrea Elena , Frechtel Gustavo Daniel , Motta Alicia Beatriz , Cerrone Gloria Edith
Published: May 2021

Background

Polycystic Ovary Syndrome (PCOS) often present metabolic disorders and hyperandrogenism (HA), facts that may influence the telomere length (TL).

Aims

To compare the absolute TL (aTL) between women with PCOS and control women, and their association with the presence of obesity and HA parameters.

Materials and methods

The PCOS group included 170 unrelated women outpatients and the control group, 64 unrelated donor women. Anthropometric, biochemical-clinical parameters and androgen profile were determined. The PCOS patients were divided accordingly to the presence of obesity and androgenic condition. The aTL was determined from peripheral blood leukocytes by Real Time quantitative PCR.

Results

Women with PCOS exhibited a significantly longer aTL than controls after age adjustment (p=0.001). A stepwise multivariate linear regression in PCOS women, showed that WC (waist circumference) contributed negatively (b=-0.17) while testosterone levels contributed positively (b=7.24) to aTL. The non-Obese PCOS (noOB-PCOS) presented the longest aTL when compared to controls (p=0.001). Meanwhile, the aTL was significantly higher in the hyperandrogenic PCOS phenotype (HA-PCOS) than in the controls (p=0.001) and non hyperandrogenic PCOS phenotype (NHA-PCOS) (p=0.04). Interestingly, when considering obesity and HA parameters in PCOS, HA exerts the major effect over the aTL as non-obese HA exhibited the lengthiest aTL (23.9 ± 13.13 Kbp). Conversely, the obese NHA patients showed the shortest aTL (16.5 ± 10.59 Kbp).

Conclusions

Whilst a shorter aTL could be related to the presence of obesity, a longer aTL would be associated with HA phenotype. These findings suggest a balance between the effect produced by the different metabolic and hormonal components, in PCOS women.
Synthesis of Bio-Cellulose Acetate Membrane From Coconut Juice Residues for Carbon Dioxide Removal From Biogas in Membrane Unit
Authors: Khamwichit Attaso , Wattanasit Sakkarin , Dechapanya Wipawee
Published: May 2021

The rapid growth of energy demand and consumption from fossil fuels has been of great concern since the last decade. Renewable energy, including biogas production from wastes, has been studied to ease up the energy crisis problems. This study aims to synthesize bio-cellulose acetate (CA) membranes from agricultural waste and to study its efficiency in the removal of CO2 from biogas. The bio-CA membranes were synthesized from acetylation of bacterial cellulose (BC) and obtained from coconut juice residues (CJRs). The results showed that both chemical and physical characteristics of the bio-CA membrane were compared with those of the chemical CA membranes. The CO2 removal capacity of the bio-CA membranes was tested in a membrane separation unit. The maximum CO2 selectivity of 29.53 was achieved when using the bio-CA membrane with a thickness of 0.05 mm under the feed pressure of 0.1 MPa. Thick CA membranes exhibited better CO2 selectivity performance, particularly at low operating pressure. However, the CO2/CH4 separation factor decreased in the high-pressure region, probably because of the plasticization of the gas components. Eco-efficiency was evaluated to determine the optimal process conditions. In terms of eco-efficiency, the results suggested that the optimal condition was a bio-CA membrane of 0.05-mm thickness and pressure of 0.1 MPa. The implication of this study is promoting a zero-waste environment in which the agricultural residues could be potentially used in the synthesis of high-value CA membranes for biogas purification applications in energy production.
Human Population Density is a Poor Predictor of Debris in the Environment
Authors: Schuyler Qamar , Wilcox Chris , Lawson T. J. , Ranatunga R. R. M. K. P. , Hu Chieh-Shen , Global Plastics Project Partners  , Hardesty Britta Denise
Published: May 2021

There have been a variety of attempts to model and quantify the amount of land-based waste entering the world’s oceans, most of which rely heavily on global estimates of population density as the key driving factor. Using empirical data collected in seven different countries/territories (China, Kenya, South Africa, South Korea, Sri Lanka, Taiwan and Vietnam), we assessed a variety of different factors that may drive plastic leakage to the environment. These factors included both globally available GIS data as well as observations made at a site level. While the driving factors that appear in the best models varied from country to country, it is clear from our analyses that population density is not the best predictor of plastic leakage to the environment. Factors such as land use, infrastructure and socio-economics, as well as local site-level variables (e.g., visible humans, vegetation height, site type) were more strongly correlated with plastic in the environment than was population density. This work highlights the importance of gathering empirical data and establishing regular monitoring programs not only to form accurate estimates of land-based waste entering the ocean, but also to be able to evaluate the effectiveness of land-based interventions.
The Timing and Abundance of IL-2Rβ (CD122) Expression Control Thymic iNKT Cell Generation and NKT1 Subset Differentiation
Authors: Won Hee Yeun , Kim Hye Kyung , Crossman Assiatu , Awasthi Parirokh , Gress Ronald E. , Park Jung-Hyun
Published: May 2021

Invariant NKT (iNKT) cells are thymus-generated innate-like T cells, comprised of three distinct subsets with divergent effector functions. The molecular mechanism that drives the lineage trifurcation of immatureiNKT cells into the NKT1, NKT2, and NKT17 subsets remains a controversial issue that remains to be resolved. Because cytokine receptor signaling is necessary foriNKT cell generation, cytokines are proposed to contribute toiNKT subset differentiation also. However, the precise roles and requirements of cytokines in these processes are not fully understood. Here, we show that IL-2Rβ, a nonredundant component of the IL-15 receptor complex, plays a critical role in both the development and differentiation of thymiciNKT cells. While the induction of IL-2Rβ expression on postselection thymocytes is necessary to drive the generation ofiNKT cells, surprisingly, premature IL-2Rβ expression on immatureiNKT cells was detrimental to their development. Moreover, while IL-2Rβ is necessary for NKT1 generation, paradoxically, we found that the increased abundance of IL-2Rβ suppressed NKT1 generation without affecting NKT2 and NKT17 cell differentiation. Thus, the timing and abundance of IL-2Rβ expression controliNKT lineage fate and development, thereby establishing cytokine receptor expression as a critical regulator of thymiciNKT cell differentiation.
A Small Molecule Antagonist of PD-1/PD-L1 Interactions Acts as an Immune Checkpoint Inhibitor for NSCLC and Melanoma Immunotherapy
Authors: Wang Yuanyuan , Gu Tingxuan , Tian Xueli , Li Wenwen , Zhao Ran , Yang Wenqian , Gao Quanli , Li Tiepeng , Shim Jung-Hyun , Zhang Chengjuan , Liu Kangdong , Lee Mee-Hyun
Published: May 2021

Immune checkpoint inhibitors, such as monoclonal antibodies targeting programmed death 1 (PD-1) and programmed death ligand-1 (PD-L1), have achieved enormous success in the treatment of several cancers. However, monoclonal antibodies are expensive to produce, have poor tumor penetration, and may induce autoimmune side effects, all of which limit their application. Here, we demonstrate that PDI-1 (also name PD1/PD-L1 inhibitor 1), a small molecule antagonist of PD-1/PD-L1 interactions, shows potent anti-tumor activityin vitroandin vivoand acts by relieving PD-1/PD-L1-induced T cell exhaustion. We show that PDI-1 binds with high affinity to purified human and mouse PD-1 and PD-L1 proteins and is a competitive inhibitor of human PD-1/PD-L1 bindingin vitro. Incubation ofex vivoactivated human T cells with PDI-1 enhanced their cytotoxicity towards human lung cancer and melanoma cells, and concomitantly increased the production of granzyme B, perforin, and inflammatory cytokines. Luciferase reporter assays showed that PDI-1 directly increases TCR-mediated activation of NFAT in a PD-1/PD-L1-dependent manner. In two syngeneic mouse tumor models, the intraperitoneal administration of PDI-1 reduced the growth of tumors derived from human PD-L1-transfected mouse lung cancer and melanoma cells; increased and decreased the abundance of tumor-infiltrating CD8+ and FoxP3+ CD4+ T cells, respectively; decreased the abundance of PD-L1-expressing tumor cells, and increased the production of inflammatory cytokines. The anti-tumor effect of PDI-1in vivowas comparable to that of the anti-PD-L1 antibody atezolizumab. These results suggest that the small molecule inhibitors of PD-1/PD-L1 may be effective as an alternative or complementary immune checkpoint inhibitor to monoclonal antibodies.
Multicohort Analysis Identifies Monocyte Gene Signatures to Accurately Monitor Subset-Specific Changes in Human Diseases
Authors: Vallania Francesco , Zisman Liron , Macaubas Claudia , Hung Shu-Chen , Rajasekaran Narendiran , Mason Sonia , Graf Jonathan , Nakamura Mary , Mellins Elizabeth D. , Khatri Purvesh
Published: May 2021

Monocytes are crucial regulators of inflammation, and are characterized by three distinct subsets in humans, of which classical and non-classical are the most abundant. Different subsets carry out different functions and have been previously associated with multiple inflammatory conditions. Dissecting the contribution of different monocyte subsets to disease is currently limited by samples and cohorts, often resulting in underpowered studies and poor reproducibility. Publicly available transcriptome profiles provide an alternative source of data characterized by high statistical power and real-world heterogeneity. However, most transcriptome datasets profile bulk blood or tissue samples, requiring the use of in silico approaches to quantify changes in cell levels. Here, we integrated 853 publicly available microarray expression profiles of sorted human monocyte subsets from 45 independent studies to identify robust and parsimonious gene expression signatures, consisting of 10 genes specific to each subset. These signatures maintain their accuracy regardless of disease state in an independent cohort profiled by RNA-sequencing and are specific to their respective subset when compared to other immune cells from both myeloid and lymphoid lineages profiled across 6160 transcriptome profiles. Consequently, we show that these signatures can be used to quantify changes in monocyte subsets levels in expression profiles from patients in clinical trials. Finally, we show that proteins encoded by our signature genes can be used in cytometry-based assays to specifically sort monocyte subsets. Our results demonstrate the robustness, versatility, and utility of our computational approach and provide a framework for the discovery of new cellular markers.
Deciphering the Complexity of 3D Chromatin Organization Driving Lymphopoiesis and Lymphoid Malignancies
Authors: Scourzic Laurianne , Salataj Eralda , Apostolou Effie
Published: May 2021

Proper lymphopoiesis and immune responses depend on the spatiotemporal control of multiple processes, including gene expression, DNA recombination and cell fate decisions. High-order 3D chromatin organization is increasingly appreciated as an important regulator of these processes and dysregulation of genomic architecture has been linked to various immune disorders, including lymphoid malignancies. In this review, we present the general principles of the 3D chromatin topology and its dynamic reorganization during various steps of B and T lymphocyte development and activation. We also discuss functional interconnections between architectural, epigenetic and transcriptional changes and introduce major key players of genomic organization in B/T lymphocytes. Finally, we present how alterations in architectural factors and/or 3D genome organization are linked to dysregulation of the lymphopoietic transcriptional program and ultimately to hematological malignancies.
Characterization and Manipulation of the Crosstalk Between Dendritic and Natural Killer Cells Within the Tumor Microenvironment
Authors: Jacobs Benedikt , Gebel Veronika , Heger Lukas , Grèze Victoria , Schild Hansjörg , Dudziak Diana , Ullrich Evelyn
Published: May 2021

Cellular therapy has entered the daily clinical life with the approval of CAR T cell therapeutics and dendritic cell (DCs) vaccines in the US and the EU. In addition, numerous other adoptive cellular products, including natural killer (NK) cells, are currently evaluated in early phase I/ II clinical trials for the treatment of cancer patients. Despite these promising accomplishments, various challenges remain to be mastered in order to ensure sustained therapeutic success. These include the identification of strategies by which tumor cells escape the immune system or establish an immunosuppressive tumor microenvironment (TME). As part of the innate immune system, DCs and NK cells are both present within the TME of various tumor entities. While NK cells are well known for their intrinsic anti-tumor activity by their cytotoxicity capacities and the secretion of pro-inflammatory cytokines, the role of DCs within the TME is a double-edged sword as different DC subsets have been described with either tumor-promoting or -inhibiting characteristics. In this review, we will discuss recent findings on the interaction of DCs and NK cells under physiological conditions and within the TME. One focus is the crosstalk of various DC subsets with NK cells and their impact on the progression or inhibition of tumor growth. In addition, we will provide suggestions to overcome the immunosuppressive outcome of the interaction of DCs and NK cells within the TME.
Can Celiac Disease Be Prevented?
Authors: Auricchio Renata , Troncone Riccardo
Published: May 2021

Celiac disease (CD) is an autoimmune disorder triggered by gluten in genetically susceptible individuals characterized by a variable combination of gluten-dependent symptoms, presence of specific autoantibodies and enteropathy. The health burden of CD is considerable, as it reduces quality of life  and, at a societal level, has extensive negative economic consequences. Prevention strategies are based on the identification of at-risk subjects and identification and elimination of risk factors. A number of prospective observational and interventional studies conducted on the general population, and more often in subjects at-risk, have given important information on the natural history of the disease. Both genetic and environmental factors have been identified with the former, in particular histocompatibility genes, playing a major role. Environmental factors, some operating already before birth, have been identified, with feeding pattern in the first year of life (breast feeding, amount and time of introduction of gluten) and infections being the most relevant. Prospective studies have also allowed the identification of biomarkers predictive of the disease which in perspective could better define the population on which to intervene. Interventions have been so far limited to modifications of feeding patterns. However, as also learnt from diseases that share with CD genetic risk factors and mechanisms of damage, such as type 1 diabetes (T1D), future strategies may be envisaged based on protection from infections, manipulation of microbiota, intervention on T cells.
Inducible Tertiary Lymphoid Structures: Promise and Challenges for Translating a New Class of Immunotherapy
Authors: Aoyama Shota , Nakagawa Ryosuke , Mulé James J. , Mailloux Adam W.
Published: May 2021

Tertiary lymphoid structures (TLS) are ectopically formed aggregates of organized lymphocytes and antigen-presenting cells that occur in solid tissues as part of a chronic inflammation response. Sharing structural and functional characteristics with conventional secondary lymphoid organs (SLO) including discrete T cell zones, B cell zones, marginal zones with antigen presenting cells, reticular stromal networks, and high endothelial venues (HEV), TLS are prominent centers of antigen presentation and adaptive immune activation within the periphery. TLS share many signaling axes and leukocyte recruitment schemes with SLO regarding their formation and function. In cancer, their presence confers positive prognostic value across a wide spectrum of indications, spurring interest in their artificial induction as either a new form of immunotherapy, or as a means to augment other cell or immunotherapies. Here, we review approaches for inducible (iTLS) that utilize chemokines, inflammatory factors, or cellular analogues vital to TLS formation and that often mirror conventional SLO organogenesis. This review also addresses biomaterials that have been or might be suitable for iTLS, and discusses remaining challenges facing iTLS manufacturing approaches for clinical translation.
Hard to Manage? Dynamics of Soft-Shell Crab in the Newfoundland and Labrador Snow Crab Fishery
Authors: Mullowney Darrell R.J. , Baker Krista D. , Pantin Julia R.
Published: May 2021

Capture of recently molted soft-shell crab in the Newfoundland and Labrador (NL) snow crab (Chionoecetes opilio) fishery is undesirable due to resource wastage associated with low meat yield and supposed high mortality rates upon discard. This study is intended to formalize best-practice management advice for avoidance of soft-shell crab in the fishery. The study investigates factors affecting soft-shell incidence in the catch across a large geographic stock range encompassing dynamic habitat and contrasting harvest rate strategies. The results demonstrate an interaction between seasonality and harvest rate in governing soft-shell crab levels in the fishery. Greatest potential for high soft-shell incidence occurs in late-spring or summer (June–July) fisheries in warm water populations subjected to heavy fishing pressure, with warm water populations shown to be associated with earlier molting periods. The study concludes that the optimal time to harvest snow crab is during winter or early spring, and advises that wherever winter or early spring fisheries are not possible, a best-practice management strategy is to minimize wastage by maintaining a strong residual biomass of large hard-shell males in the population at all times. This strategy is easily enabled by consistent application of low exploitation rates.
Amino Acid δ15N Can Detect Diet Effects on Pollution Risks for Yellow-Legged Gulls Overlooked by Trophic Position
Authors: Bode Antonio , Besada Victoria , Pérez-Fernández Begoña , Viñas Lucía
Published: May 2021

The use of top-consumers as bioindicators of the health of food webs is hampered by uncertainties in their effective use of resources. In this study, the abundance of stable nitrogen isotopes in amino acids from homogenised eggs of the Yellow-legged Gull (Larus michahellis) allowed to identify variations in trophic resource exploitation between geographically adjacent nesting colonies in the Ria de Vigo (NW Spain) that exhibited marked differences in pollutants. Eggs from nests in the Cíes Islands (located in a National Park) showed a large variability in stable carbon and nitrogen isotopes in bulk egg content encompassing that of eggs from Vigo city (a major fishing harbour). However, both colonies differed in the relative concentration and abundance of nitrogen isotopes of lysine, an essential amino acid present in marine prey, but also extensively used in feed stocks for poultry and swine. Notwithstanding the similarity in trophic position for both colonies, gulls from Cíes Islands may have acquired a substantial fraction of lysine from garbage dump sites, while those of the urban colony relied on fish discards. This unexpected conclusion is partly supported by the large variability reported for gull’s diet in this region and calls for detailed estimations of diet when assessing the conservation status and pollution risks of marine ecosystems.
Reducing Contact Stress of the Surface by Modifying Different Hardness of Femoral Head and Cup in Hip Prosthesis
Authors: Saputra Eko , Budiwan Anwar Iwan , Jamari J. , Heide Emile van der
Published: May 2021

The wear of hip prosthesis due to applied load and sliding distance during the patient's daily activity cannot be avoided. Wear causes osteolysis or metallosis due to the wear debris produced by the wear process. Several methods were used to reduce wear in metal-on-metal hip prostheses. One of the efforts performed to reduce wear was the differential-hardness concept. Based on the literature, the fine surface roughness of the femoral head are the reason why the hip prosthesis with differential-hardness reduces wear. Besides, the differential-hardness will contribute to the difference of modulus elasticity then influenced the contact stress on the surface contact. According to Archard's wear law, wear on the material pair is affected by contact stress. Therefore, the analysis of contact stress on the hip prosthesis with differential-hardness is important to investigate. The investigation performed by the static contact of two-dimensional axisymmetric with frictionless by using finite element simulation. The simulated models are the alumina vs. alumina, alumina vs. SS316L, CoCr vs. CoCr, CoCr vs. SS316L, and SS316L vs. UHMWPE. The purpose of this study is to determine the contact stress on the surface contact due to differential-hardness of the femoral head and cup. The results of simulations show that the differential-hardness marked by differences in the modulus of elasticity can reduce the contact stress on the surface contact if compare with the similar hardness.
Low-Contrast High-Pass Visual Acuity Might Help to Detect Glaucoma Damage: A Structure-Function Analysis
Authors: Wen Yun , Chen Zidong , Zuo Chengguo , Yang Yangfan , Xu Jiangang , Kong Yang , Cheng Hui , Yu Minbin
Published: May 2021

Purpose: The conventional visual acuity (VA) test is not sensitive enough to detect glaucoma macular damage. We aimed to investigate whether VA measurements using low-contrast high-pass optotypes are more sensitive to macular dysfunction in glaucoma and to find the potential structural basis of this difference.

Methods: A total of 147 subjects were recruited, including 118 patients with glaucoma (mean age: 46.08 ± 14.64 years) and 29 healthy controls (mean age: 39.83 ± 9.81 years). For each participant, monocular best-corrected VA was measured using a conventional chart and six high-pass charts at 100, 50, 10, 5, 2.5, and 1.25% contrast levels, respectively. The macular retinal thickness and circumpapillary retinal nerve fiber layer (cpRNFL) thickness of all the glaucoma patients were obtained by spectral-domain optical coherence tomography (SD-OCT).

Results: Compared with healthy subjects, glaucoma patients with normal vision demonstrated worse VAs in high-pass acuity measurements (0.22–0.93 vs. 0.28–1.08, p < 0.05). Receiver operating characteristic curve (ROC) showed that 1.25% low-contrast high-pass VA was optimal for discriminating between the controls and glaucoma patients (AUC: 0.918, p < 0.001; sensitivity: 77.33%; specificity: 96.55%). Compared with conventional VA, 1.25% high-pass VA correlated better with nasal-side macular retinal ganglion cell (RGC)-related parameters (r = −0.419 to −0.446 vs. r = −0.538 to −0.582; Fisher's Z transformation, pz < 0.05). There was no difference in the strength of correlations between the VAs measured using different charts and cpRNFL thickness (Fisher's Z transformation; pz > 0.05).

Conclusions: VA measurement taken with low-contrast (1.25%) high-pass acuity chart is more sensitive in detecting central visual loss in glaucoma than that taken with the conventional chart. Macular RGC damage appears to be associated with low-contrast (1.25%) high-pass visual loss in glaucomatous eyes.
ChIP-seq Analysis of the Global Regulator Vfr Reveals Novel Insights Into the Biocontrol Agent Pseudomonas protegens FD6
Authors: Zhang Qingxia , Xing Chenglin , Kong Xiangwei , Wang Cheng , Chen Xijun
Published: May 2021

Many Pseudomonas protegens strains produce the antibiotics pyoluteorin (PLT) and 2,4-diacetylphloroglucinol (2,4-DAPG), both of which have antimicrobial properties. The biosynthesis of these metabolites is typically controlled by multiple regulatory factors. Virulence factor regulator (Vfr) is a multifunctional DNA-binding regulator that modulates 2,4-DAPG biosynthesis in P. protegens FD6. However, the mechanism by which Vfr regulates this process remains unclear. In the present study, chromatin immunoprecipitation of FLAG-tagged Vfr and nucleotide sequencing analysis were used to identify 847 putative Vfr binding sites in P. protegens FD6. The consensus P. protegens Vfr binding site predicted from nucleotide sequence alignment is TCACA. The qPCR data showed that Vfr positively regulates the expression of phlF and phlG, and the expression of these genes was characterized in detail. The purified recombinant Vfr bound to an approximately 240-bp fragment within the phlF and phlG upstream regions that harbor putative Vfr consensus sequences. Using electrophoretic mobility shift assays, we localized Vfr binding to a 25-bp fragment that contains part of the Vfr binding region. Vfr binding was eliminated by mutating the TACG and CACA sequences in phlF and phlG, respectively. Taken together, our results show that Vfr directly regulates the expression of the 2,4-DAPG operon by binding to the upstream regions of both the phlF and phlG genes. However, unlike other Vfr-targeted genes, Vfr binding to P. protegens FD6 does not require an intact binding consensus motif. Furthermore, we demonstrated that vfr expression is autoregulated in this bacterium. These results provide novel insights into the regulatory role of Vfr in the biocontrol agent P. protegens.
Novel Identification of Bacterial Epigenetic Regulations Would Benefit From a Better Exploitation of Methylomic Data
Authors: Payelleville Amaury , Brillard Julien
Published: May 2021

DNA methylation can be part of epigenetic mechanisms, leading to cellular subpopulations with heterogeneous phenotypes. While prokaryotic phenotypic heterogeneity is of critical importance for a successful infection by several major pathogens, the exact mechanisms involved in this phenomenon remain unknown in many cases. Powerful sequencing tools have been developed to allow the detection of the DNA methylated bases at the genome level, and they have recently been extensively applied on numerous bacterial species. Some of these tools are increasingly used for metagenomics analysis but only a limited amount of the available methylomic data is currently being exploited. Because newly developed tools now allow the detection of subpopulations differing in their genome methylation patterns, it is time to emphasize future strategies based on a more extensive use of methylomic data. This will ultimately help to discover new epigenetic gene regulations involved in bacterial phenotypic heterogeneity, including during host-pathogen interactions.
NBD-Based Environment-Sensitive Fluorescent Probes for the Human Ether-a-Go-Go–Related Gene Potassium Channel
Authors: Li Qi , Chai Lijuan , Dong Gaopan , Zhang Xiaomeng , Du Lupei
Published: May 2021

Three environment-sensitive probes were developed for the hERG channel based on the nitrobenzoxadiazole fluorophore herein. After careful evaluation, probes M1 and M3 were found to have a high affinity for imaging the hERG channel in the cell-based experiment. Compared with other fluorescent labeling technologies (such as fluorescent proteins), these probes afford a convenient and economical method to determine hERG channel in vitro and in cellulo. Therefore, these probes are expected to be applicable for usage in physiological and pathological studies of hERG channels and have the potential to establish a screening system for hERG channels.
Endothelial Dysfunction and Impaired Neurovascular Coupling Responses Precede Cognitive Impairment in a Mouse Model of Geriatric Sepsis
Authors: Csipo Tamas , Cassidy Benjamin R. , Balasubramanian Priya , Drevets Douglas A. , Ungvari Zoltan I. , Yabluchanskiy Andriy
Published: May 2021

Sepsis is a life-threatening condition, the incidence of which is significantly increased in elderly patients. One of the long-lasting effects of sepsis is cognitive impairment defined as a new deficit or exacerbation of preexisting deficits in global cognition or executive function. Normal brain function is dependent on moment-to-moment adjustment of cerebral blood flow to match the increased demands of active brain regions. This homeostatic mechanism, termed neurovascular coupling (NVC, also known as functional hyperemia), is critically dependent on the production of vasodilator NO by microvascular endothelial cells in response to mediators released from activated astrocytes. The goal of this study was to test the hypothesis that sepsis in aging leads to impairment of NVC responses early after treatment and that this neurovascular dysfunction associates with impairments in cognitive performance and vascular endothelial dysfunction. To test this hypothesis, we used a commonly studied bacterial pathogen, Listeria monocytogenes, to induce sepsis in experimental animals (males, 24 months of age) and subjected experimental animals to a standard clinical protocol of 3 doses of ampicillin i.p. and 14 days of amoxicillin added to the drinking water. NVC responses, endothelial function and cognitive performance were measured in septic and age-matched control groups within 14 days after the final antibiotic treatment. Our data demonstrate that sepsis in aging significantly impairs NVC responses measured in somatosensory cortex during whisker stimulation, significantly impairs endothelial function in isolated and pressure cannulated aorta rings in response to acetylcholine stimulation. No significant impairment of cognitive function in post-sepsis aged animals has been observed when measured using the PhenoTyper homecage based system. Our findings suggest that sepsis-associated endothelial dysfunction and impairment of NVC responses may contribute to long-term cognitive deficits in older sepsis survivors.
Developmental Characterization of Schizophrenia-Associated Gene Zswim6 in Mouse Forebrain
Authors: Chang Chuan-Chie , Kuo Hsiao-Ying , Chen Shih-Yun , Lin Wan-Ting , Lu Kuan-Ming , Saito Tetsuichiro , Liu Fu-Chin
Published: May 2021

Schizophrenia is a devastating neuropsychiatric disease with a globally 1% life-long prevalence. Clinical studies have linked Zswim6 mutations to developmental and neurological diseases, including schizophrenia. Zswim6’s function remains largely unknown. Given the involvement of Zswim6 in schizophrenia and schizophrenia as a neurodevelopmental disease, it is important to understand the spatiotemporal expression pattern of Zswim6 in the developing brain. Here, we performed a comprehensive analysis of the spatiotemporal expression pattern of Zswim6 in the mouse forebrain by in situ hybridization with radioactive and non-radioactive-labeled riboprobes. Zswim6 mRNA was detected as early as E11.5 in the ventral forebrain. At E11.5–E13.5, Zswim6 was highly expressed in the lateral ganglionic eminence (LGE). The LGE consisted of two progenitor populations. Dlx+;Er81+ cells in dorsal LGE comprised progenitors of olfactory bulb interneurons, whereas Dlx+;Isl1+ progenitors in ventral LGE gave rise to striatal projection neurons. Zswim6 was not colocalized with Er81 in the dorsal LGE. In the ventral LGE, Zswim6 was colocalized with striatal progenitor marker Nolz-1. Zswim6 was highly expressed in the subventricular zone (SVZ) of LGE in which progenitors undergo the transition from proliferation to differentiation. Double labeling showed that Zswim6 was not colocalized with proliferation marker Ki67 but was colocalized with differentiation marker Tuj1 in the SVZ, suggesting Zswim6 expression in early differentiating neurons. Zswim6 was also expressed in the adjacent structures of medial and caudal ganglionic eminences (MGE, CGE) that contained progenitors of cortical interneurons. At E15.5 and E17.5, Zswim6 was expressed in several key brain regions that were involved in the pathogenesis of schizophrenia, including the striatum, cerebral cortex, hippocampus, and medial habenular nucleus. Zswim6 was persistently expressed in the postnatal brain. Cell type analysis indicated that Zswim6 mRNA was colocalized with D1R-expressing striatonigral and D2R-expressing striatopallidal neurons of the adult striatum with a higher colocalization in striatopallidal neurons. These findings are of particular interest as striatal dopamine D2 receptors are known to be involved in the pathophysiology of schizophrenia. In summary, the comprehensive analysis provides an anatomical framework for the study of Zswim6 function and Zswim6-associated neurological disorders.
Embodying Stressful Events: No Difference in Subjective Arousal and Neural Correlates Related to Immersion, Interoception, and Embodied Mentalization
Authors: De Coninck Sarah , Aben Bart , Van den Bussche Eva , Mariën Peter , Van Overwalle Frank
Published: May 2021

Repetitive thought about oneself, including one’s emotions, can lead to both adaptive and maladaptive effects. Construal level of repetitive self-referential thought might moderate this. During interoception, which engages areas such as the insula, the anterior and/or posterior cingulate cortex (PCC) and the somatosensory cortex, concrete low level construal self-referential thought is applied, which has been shown to lead to more positive emotions after upsetting events. Contrarily, during immersion, related to neural activity in the default mode network (DMN), abstract high level construal self-referential thought is applied, which is linked to depression. The current study investigated whether the integration of concrete and abstract self-referential thought by means of embodied mentalization leads to less subjective arousal, decreased DMN activity and increased somatosensory activity as compared to immersion, and to more DMN activity as compared to interoception. In the fMRI scanner, participants imagined stressful events while adopting immersion, interoception or embodied mentalization. After each imagined stressful event, participants rated their subjective arousal and how difficult it was to apply the mode of self-referential thought. Results showed that participants felt that immersion was easier to apply than embodied mentalization. However, no differences in subjective arousal or neural activity were found between immersion, interoception and embodied mentalization. Possible reasons for this lack of significant differences are discussed.
Calibrating 3D Scanner in the Coordinate System of Optical Tracker for Image-To-Patient Registration
Authors: Li Wenjie , Fan Jingfan , Li Shaowen , Tian Zhaorui , Zheng Zhao , Ai Danni , Song Hong , Yang Jian
Published: May 2021

Three-dimensional scanners have been widely applied in image-guided surgery (IGS) given its potential to solve the image-to-patient registration problem. How to perform a reliable calibration between a 3D scanner and an external tracker is especially important for these applications. This study proposes a novel method for calibrating the extrinsic parameters of a 3D scanner in the coordinate system of an optical tracker. We bound an optical marker to a 3D scanner and designed a specified 3D benchmark for calibration. We then proposed a two-step calibration method based on the pointset registration technique and nonlinear optimization algorithm to obtain the extrinsic matrix of the 3D scanner. We applied repeat scan registration error (RSRE) as the cost function in the optimization process. Subsequently, we evaluated the performance of the proposed method on a recaptured verification dataset through RSRE and Chamfer distance (CD). In comparison with the calibration method based on 2D checkerboard, the proposed method achieved a lower RSRE (1.73 mm vs. 2.10, 1.94, and 1.83 mm) and CD (2.83 mm vs. 3.98, 3.46, and 3.17 mm). We also constructed a surgical navigation system to further explore the application of the tracked 3D scanner in image-to-patient registration. We conducted a phantom study to verify the accuracy of the proposed method and analyze the relationship between the calibration accuracy and the target registration error (TRE). The proposed scanner-based image-to-patient registration method was also compared with the fiducial-based method, and TRE and operation time (OT) were used to evaluate the registration results. The proposed registration method achieved an improved registration efficiency (50.72 ± 6.04 vs. 212.97 ± 15.91 s in the head phantom study). Although the TRE of the proposed registration method met the clinical requirements, its accuracy was lower than that of the fiducial-based registration method (1.79 ± 0.17 mm vs. 0.92 ± 0.16 mm in the head phantom study). We summarized and analyzed the limitations of the scanner-based image-to-patient registration method and discussed its possible development.
Severe Dementia Predicts Weight Loss by the Time of Death
Authors: Ciciliati Aline Maria M. , Adriazola Izabela Ono , Souza Farias-Itao Daniela , Pasqualucci Carlos Augusto , Leite Renata Elaine Paraizo , Nitrini Ricardo , Grinberg Lea T. , Jacob-Filho Wilson , Suemoto Claudia Kimie
Published: May 2021

Background: Body mass index (BMI) in midlife is associated with dementia. However, the association between BMI and late-life obesity is controversial. Few studies have investigated the association between BMI and cognitive performance near the time of death using data from autopsy examination. We aimed to investigate the association between BMI and dementia in deceased individuals who underwent a full-body autopsy examination.

Methods: Weight and height were measured before the autopsy exam. Cognitive function before death was investigated using the Clinical Dementia Rating (CDR) scale. The cross-sectional association between BMI and dementia was investigated using linear regression models adjusted for sociodemographic and clinical variables.

Results: We included 1,090 individuals (mean age 69.5 ± 13.5 years old, 46% women). Most participants (56%) had a normal BMI (18.5–24.9 kg/m2), and the prevalence of dementia was 16%. Twenty-four percent of the sample had cancer, including 76 cases diagnosed only by the autopsy examination. Moderate and severe dementia were associated with lower BMI compared with participants with normal cognition in fully adjusted models (moderate: β = −1.92, 95% CI = −3.77 to −0.06, p = 0.042; severe: β = −2.91, 95% CI = −3.97 to −1.86, p < 0.001).

Conclusion: BMI was associated with moderate and severe dementia in late life, but we did not find associations of BMI with less advanced dementia stages.
Monocyte-Derived Macrophages Contribute to Chitinase Dysregulation in Amyotrophic Lateral Sclerosis: A Pilot Study
Authors: Gaur Nayana , Huss Elena , Prell Tino , Steinbach Robert , Guerra Joel , Srivastava Akash , Witte Otto W. , Grosskreutz Julian
Published: May 2021

Neuroinflammation significantly contributes to Amyotrophic Lateral Sclerosis (ALS) pathology. In lieu of this, reports of elevated chitinase levels in ALS are interesting, as they are established surrogate markers of a chronic inflammatory response. While post-mortem studies have indicated glial expression, the cellular sources for these moieties remain to be fully understood. Therefore, the objective of this pilot study was to examine whether the peripheral immune system also contributes to chitinase dysregulation in ALS. The temporal expression of CHIT1, CHI3L1, and CHI3L2 in non-polarized monocyte-derived macrophages (MoMas) from ALS patients and healthy controls (HCs) was examined. We demonstrate that while CHIT1 and CHI3L1 display similar temporal expression dynamics in both groups, profound between-group differences were noted for these targets at later time-points i.e., when cells were fully differentiated. CHIT1 and CHI3L1 expression were significantly higher in MoMas from ALS patients at both the transcriptomic and protein level, with CHI3L1 levels also being influenced by age. Conversely, CHI3L2 expression was not influenced by disease state, culture duration, or age. Here, we demonstrate for the first time, that in ALS, circulating immune cells have an intrinsically augmented potential for chitinase production that may propagate chronic neuroinflammation, and how the ageing immune system itself contributes to neurodegeneration.