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Exploiting Caenorhabditis elegans to discover human gut microbiota-mediated intervention strategies in protein conformational diseases

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Neural Regeneration Research 2022年第10期17卷 2203-2204页

作者： daniel M.Czyż Department of Microbiology and Cell Science University of FloridaGainesvilleFLUSA

Age-dependent protein-conformational diseases(PCDs),such as Alzheimer’s disease(AD),Parkinson’s disease(PD),or amyotrophic lateral sclerosis(ALS),are characterized by misfolding and aggregation of metastable proteins present within the proteome of the affected *** evidence supports the notion that bacteria and bacterial products may be affecting the stability of these culprit host proteins and therefore influence disease progression and perhaps even its *** specific culprit proteins are associated with each disease(e.g.,Aβin AD,α-synuclein in PD,and TDP-43 in ALS),bacteria found to affect these diseases do not seem to differentiate between these specific proteins but likely affect host proteostasis in general,leading to misfolding of metastable proteins encoded within the *** evidence that supports this hypothesis comes from studies where a single bacterial genus was linked to multiple *** example,a decrease in Prevotella *** linked to constipation,a condition that precedes PD motor symptoms by as much as 20 or more years(Savica et al.,2009;Zhu et al.,2014).

关键词： diseases Alzheimer folding

Frequent low dose alcohol intake increases gastric cancer risk: the Health Examinees-gem (HEXA-g) study

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Cancer Biology & Medicine 2022年第8期19卷 1224-1234页

作者： Hwi-Won Lee Dan Huang Woo-Kyoung Shin Katherine de la torre Minkyo Song Aesun Shin Jong-Koo Lee Daehee Kang Department of Biomedical Sciences Seoul National University Graduate SchoolSeoul 03080Korea Department of Preventive Medicine Seoul National University College of MedicineSeoul 03080Korea Integrated Major in Innovative Medical Science Seoul National University Graduate SchoolSeoul 03080Korea Department of Family Medicine Seoul National University HospitalSeoul 03080Korea

Objective:Epidemiological studies indicate that alcohol increases gastric cancer(gC)risk,yet most studies have focused on heavy alcohol intake,leaving other factors understudied.A comprehensive investigation of the effects of the frequency and amount of alcohol intake may help elucidate the gC risk associated with drinking ***:The Health Examinees-gem(HEXA-g)study,a community-based large-scale prospective cohort study,enrolled Korean adults 40–69 years of age between the years 2004 and *** gC cases were identified through linkage to Korea Central Cancer Registry data until December 31,***-reported questionnaires were used to survey alcohol consumption-related factors(duration,frequency,amount,and type of alcoholic beverages).The frequency and amount of alcohol consumption were combined to explore gC risk according to 4 drinking patterns:“infrequent-light”,“frequent-light”,“infrequent-heavy”,and“frequent-heavy”.We used Cox proportional hazard models to estimate the adjusted hazard ratios(HRs)and 95%confidence intervals(CIs),and investigate the relationship between alcohol intake and gC ***:A total of 128,218 participants were included in the *** an average follow-up period of 8.6 years,462 men and 385 women were diagnosed with *** men,current drinkers showed a 31%greater risk of gC than non-drinkers(HR 1.31,95%CI 1.03–1.66),whereas no significant association was observed in *** men,gC risk was associated with a higher frequency(P trend 0.02)and dose of ethanol intake in grams(P trend 0.03).In men,the“frequent-light”(≥5 times/week andg ethanol/day)drinking pattern was associated with a 46%greater risk of gC(HR 1.46,95%CI 1.02–2.07)than the“infrequent-light”pattern(g ethanol/day).Conclusions:This study suggests that frequent intake of alcohol,even in low quantities per session,increases gC *** research is warranted to evaluate the relationship between alcohol and gC in detai

关键词： gastric cancer alcohol consumption drinking behavior prospective cohort Health Examinees-gem(HEXA-g)study

Orchestration of occludins, claudins, catenins and cadherins as players involved in maintenance of the blood-epididymal barrier in animals and humans

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Asian Journal of Andrology 2007年第4期9卷 463-475页

作者： daniel g. Cyr Mary gregory Evemie Dube Julie Dufresne Peter T. K. Chan Louis Hermo INRS-Institut Armand Frappier Universite du Quebec 245 Hymus Boulevard Pointe Claire QC H9R 1G6 Canada Department of Urology Royal Victoria Hospital McGill University Montreal QC H3A 1A1 Canada Department of Anatomy and Cell Biology McGill University Montreal QC H3A 2B2 Canada

Although spermatozoa are formed during spermatogenesis in the testis, testicular spermatozoa are immature and cannot swim or fertilize. These critical spermatozoal functions are acquired in the epididymis where a specific luminal environment is created by the blood-epididymal barrier; proteins secreted by epididymal principal cells bind to maturing spermatozoa and regulate the maturational process of the spermatozoa. In the epididymis, epithelial cell-cell interactions are mediated by adhering junctions, necessary for cell adhesion, and by tight junctions, which form the blood-epididymal barrier. The regulation of these cellular junctions is thought to represent a key determinant in the process of sperm maturation within the epididymis. Tight junctions between adjacent principal cells permit the formation of a specific microenvironment in the lumen of the epididymis that is essential for sperm maturation. Although we have made significant progress in understanding epididymal function and the blood-epididymal barrier, using animal models, there is limited information on the human epididymis. If we are to understand the normal and pathological conditions attributable to human epididymal function, we must clearly establish the physiological, cellular and molecular regulation of the human epididymis, develop tools to characterize these functions and develop clinical strategies that will use epididymal functions to improve treatment of infertility. （Asian J Androl 2007 July; 9： 463- 475）

关键词： claudins cadherins catenins human rat mouse tight junction adherens junction

Advanced non-alcoholic steatohepatitis cirrhosis: A high-risk population for pre-liver transplant portal vein thrombosis

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World Journal of Hepatology 2017年第3期9卷 139-146页

作者： Jonathan g Stine Curtis K Argo Shawn J Pelletier daniel g Maluf Stephen H Caldwell Patrick g Northup Division of gastroenterology and Hepatology Department of Medicine Center for the Study of Coagulation Disorders in Liver Disease University of Virginia Division of Transplant Department of Surgery University of Virginia

AIMTo examine if liver transplant recipients with high-risk non-alcoholic steatohepatitis (NASH) are at increased risk for pre-transplant portal venous thrombosis. METHODSData on all liver transplants in the United States from February 2002 through September 2014 were analyzed. Recipients were sorted into three distinct groups: High-risk (age > 60, body mass index > 30 kg/m2, hypertension and diabetes), low-risk and non-NASH cirrhosis. Multivariable logistic regression models were constructed. RESULTSThirty-five thousand and seventy-two candidates underwent liver transplantation and of those organ recipients, 465 were transplanted for high-risk and 2775 for low-risk NASH. Two thousand six hundred and twenty-six (7.5%) recipients had pre-transplant portal vein thrombosis; 66 (14.2%) of the high-risk NASH group had portal vein thrombosis vs 328 (11.8%) of the low-risk NASH group. In general, all NASH recipients were less likely to be male or African American and more likely to be obese. In adjusted multivariable regression analyses, high-risk recipients had the greatest risk of pre-transplant portal vein thrombosis with OR = 2.11 (95%CI: 1.60-2.76, P CONCLUSIONLiver transplant candidates with high-risk NASH are at the greatest risk for portal vein thrombosis development prior to transplantation. These candidates may benefit from interventions to decrease their likelihood of clot formation and resultant downstream hepatic decompensating events. Prospective study is needed.

关键词： Liver transplantation Non-alcoholic fatty liver disease Portal hypertension Hepatology Coagulopathy

Mining Frequent generalized Itemsets and generalized Association Rules Without Redundancy

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Journal of Computer Science & Technology 2008年第1期23卷 77-102页

作者： daniel Kunkle 张冬晖 gene Cooperman College of Computer and Information Science Northeastern UniversityBoston

This paper presents some new algorithms to efficiently mine max frequent generalized itemsets （g-itemsets） and essential generalized association rules （g-rules）. These are compact and general representations for all frequent patterns and all strong association rules in the generalized environment. Our results fill an important gap among algorithms for frequent patterns and association rules by combining two concepts. First, generalized itemsets employ a taxonomy of items, rather than a flat list of items. This produces more natural frequent itemsets and associations such as （meat, milk） instead of （beef, milk）, （chicken, milk）, etc. Second, compact representations of frequent itemsets and strong rules, whose result size is exponentially smaller, can solve a standard dilemma in mining patterns： with small threshold values for support and confidence, the user is overwhelmed by the extraordinary number of identified patterns and associations; but with large threshold values, some interesting patterns and associations fail to be identified. Our algorithms can also expand those max frequent g-itemsets and essential g-rules into the much larger set of ordinary frequent g-itemsets and strong g-rules. While that expansion is not recommended in most practical cases, we do so in order to present a comparison with existing algorithms that only handle ordinary frequent g-itemsets. In this case, the new algorithm is shown to be thousands, and in some cases millions, of the time faster than previous algorithms. Further, the new algorithm succeeds in analyzing deeper taxonomies, with the depths of seven or more. Experimental results for previous algorithms limited themselves to taxonomies with depth at most three or four. In each of the two problems, a straightforward lattice-based approach is briefly discussed and then a classificationbased algorithm is developed. In particular, the two classification-based algorithms are MFgI_class for mining max frequent g-itemsets and EgR_cl

关键词： generalized association rules frequent generalized itemsets redundancy avoidance

Reinhold Niebuhr and Martin Luther King,Jr.:Christian Realism,Pacifism,and the Beloved Community

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International Relations and Diplomacy 2020年第1期8卷 1-13页

作者： daniel g Lang University of Lynchburg LynchburgUSA

Reinhold Niebuhr’s intellectual journey in the 1930’s away from the idealism of liberal Protestantism and the optimism of the Social gospel toward the more sober understanding of Christian realism involved,among other things,a rejection of *** conceding that the use of force in international relations is morally perilous,Niebuhr saw the utopianism of the pacifist position“to be nothing more than a capitulation to tyranny”.Martin Luther King *** Niebuhr’s Moral Man and Immoral Society and other works in seminary a generation *** he found much to praise in Niebuhr’s analysis,ultimately he rejected Niebuhr’s ***,in spite of King’s very public embrace of gandhi’s pacifism,one finds in King’s practice of non-violent resistance substantial engagement with Niebuhr’s ideas.

关键词： Christian realism utopianism ethical dualism pacifism non-violent resistance

Chronic stress sensitizes rats to pancreatitis induced by cerulein:Role of TNF-α

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World Journal of gastroenterology 2010年第44期16卷 5565-5581页

作者： marcelo g Binker Andres A Binker-Cosen daniel Richards Herbert Y gaisano Rodica H de Cosen Laura I Cosen-Binker CBRHC Research Health Center Department of Medicine and Physiology University of Toronto

AIM:To investigate chronic stress as a susceptibility factor for developing pancreatitis,as well as tumor necrosis factor-α (TNF-α) as a putative ***:Rat pancreatic acini were used to analyze the influence of TNF-α on submaximal (50 pmol/L) cholecystokinin (CCK) *** restraint (4 h every day for 21 d) was used to evaluate the effects of submaximal (0.2 μg/kg per hour) cerulein stimulation on chronically stressed ***:In vitro exposure of pancreatic acini toTNF-α disorganized the actin *** was further increased by TNF-α/CCK treatment,which additionally reduced amylase secretion,and increased trypsin and nuclear factor-κB activities in a protein-kinase-C δ and ε-dependent ***-α/CCK also enhanced caspases' activity and lactate dehydrogenase release,induced ATP loss,and augmented the ADP/ATP *** vivo,rats under chronic restraint exhibited elevated serum and pancreatic TNF-α ***,pancreatic,and lung inflammatory parameters,as well as caspases' activity in pancreatic and lung tissue,were substantially enhanced in stressed/cerulein-treated rats,which also experienced tissues' ATP loss and greater ADP/ATP *** examination revealed that stressed/cerulein-treated animals developed abundant pancreatic and lung edema,hemorrhage and leukocyte infiltrate,and pancreatic *** severity was greatly decreased by treating animals with an anti-TNF-αantibody,which diminished all inflammatory parameters,histopathological scores,and apoptotic/necrotic markers in stressed/cerulein-treated ***:In rats,chronic stress increases susceptibility for developing pancreatitis,which involves TNF-α sensitization of pancreatic acinar cells to undergo injury by physiological cerulein stimulation.

关键词： Pancreatitis Stress Tumor necrosis factor-α

Anchoring of 10-phenylphenothiazine to mesoporous silica materials:A water compatible organic photocatalyst for the degradation of pollutants

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Journal of Materials Science & Technology 2022年第8期103卷 134-143页

作者： daniel gonzález-Muñoz Almudena gómez-Avilés Carmen B.Molina Jorge Bedia Carolina Belver Jose Alemán Silvia Cabrera Organic Chemistry Department Science FacultyUniversidad Autónoma de Madrid28049 MadridSpain Chemical Engineering Department Science FacultyUniversidad Autónoma de Madrid28049 MadridSpain Institute for Advanced Research in Chemical Sciences(IAdChem) Universidad Autónoma de Madrid28049 MadridSpain Inorganic Chemistry Department Science FacultyUniversidad Autónoma de Madrid28049 MadridSpain

The application of organic photocatalysts towards the oxidation of pollutants in water is hampered by different limitations such as their insolubility in the ***,we report that the grafting of a photoorganocatalyst into mesoporous silica materials is an ideal approach to obtain effective ***,the photocatalyst 10-phenylphenothiazine(PTH)was easily anchored into three different mesoporous silica-based materials(MSN,MSU-2 and SBA-15)with different particle sizes and pore sizes through an amide bond *** materials were characterized using IR analysis,solid-state X-ray diffraction,porosity and microscopy(SEM and TEM)techniques,showing that PTH is immobilized inside the pores of the materials and its optical properties are maintained after the *** homogeneous PTH was inactive in water media,the three photocatalytic materials were active for the degradation of ***-15-AP-PTH exhibited the highest catalytic performance towards the degradation of acetaminophen and diclofenac under solar irradiation,finding in this manner a new strategy for the decontamination of pollutants.

关键词： Organic semiconductors Silica support Solar photocatalysis Water treatment Pharmaceuticals

Neoadjuvant peptide receptor radionuclide therapy for an inoperable neuroendocrine pancreatic tumor

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World Journal of gastroenterology 2009年第46期15卷 5867-5870页

作者： daniel Kaemmerer Vikas Prasad Wolfgang Daffner Dieter Hrsch günter Klppel Merten Hommann Richard P Baum Department of general and Visceral Surgery Zentralklinik Bad Berka Department of Nuclear Medicine Center for PETZentralklinik Bad Berka Department of Internal Medicine Gastroen-terologyEndocrinology and OncologyZentralklinik Bad Berka Department of Pathology University of Kiel

Pancreatic endocrine tumors are rare but are among the most common neuroendocrine neoplasms of the *** diagnosis many of them are already advanced and diff icult to *** report on an initially inoperable malignant pancreatic endocrine tumor in a 33-year-old woman,who received neoadjuvant peptide receptor radionuclide therapy(PRRT)as firstline *** resulted in a signif icant downstaging of the tumor and allowed its subsequent complete surgical ***-up for eighteen months revealed a complete *** is the first report on neoadjuvant PRRT in a neuroendocrine neoplasm with subsequent successful complete resection.

关键词： Endocrine pancreatic carcinoma Peptidereceptor radionuclide therapy Neodjuvant treatment Pancreatic surgery Molecular imaging Receptor pan-creatic endocrine tumor Computed tomography