Publications by authors named "Mark S Kuhlenschmidt"

Article Synopsis
  • Cryptosporidium is a major cause of severe diarrhea in infants and can infect immunocompromised individuals, yet research has been limited due to difficult experimental methods.* -
  • The study introduces a new platform using "air-liquid interface" (ALI) cultures from intestinal stem cells, which allows for the complete life cycle of C. parvum to be developed and studied in vitro.* -
  • This ALI culture method facilitates significant expansion of the parasite, supports the production of infectious oocysts, and allows for advanced genetic studies using CRISPR/Cas9, opening up new avenues for research on Cryptosporidium biology and its interactions with hosts.*
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Among the obstacles hindering research is the lack of an culture system that supports complete life development and propagation. This major barrier has led to a shortage of widely available anti- antibodies and a lack of markers for staging developmental progression. Previously developed antibodies against were raised against extracellular stages or recombinant proteins, leading to antibodies with limited reactivity across the parasite life cycle.

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Cryptosporidium parvum is the second leading cause of persistent diarrhea among children in low-resource settings. This study examined the effect of oregano essential oil (OEO) and carvacrol (CV) on inhibition of C. parvum infectivity in vitro.

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Runoff from animal production facilities contains various microbial pathogens which pose a health hazard to both humans and animals. Rotavirus is a frequently detected pathogen in agricultural runoff and the leading cause of death among children around the world. Diarrheal infection caused by rotavirus causes more than two million hospitalizations and death of more than 500,000 children every year.

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Human milk oligosaccharides (HMOs) have antimicrobial and immunomodulatory actions. It has previously been reported that these oligosaccharides contribute to the reduced duration of rotavirus-induced diarrhea in pigs. We measured the effects of HMOs and prebiotic oligosaccharides on immune cell populations from noninfected and rotavirus-infected pigs.

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Cryptosporidiosis is a serious diarrheal disease in immunocompromised patients and malnourished children, and treatment is complicated by a lack of adequate drugs. Recent studies suggest that the natural occurrence of a small gatekeeper residue in serine threonine calcium-dependent protein kinase 1 (CDPK1) of Cryptosporidium parvum might be exploited to target this enzyme and block parasite growth. Here were explored the potency with which a series of pyrazolopyrimidine analogs, which are selective for small gatekeeper kinases, inhibit C.

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Background: Metastasis accounts for the majority of deaths from cancer. Although tumor microenvironment has been shown to have a significant impact on the initiation and/or promotion of metastasis, the mechanism remains elusive. We previously reported that HCT-8 colon cancer cells underwent a phenotypic transition from an adhesive epithelial type (E-cell) to a rounded dissociated type (R-cell) via soft substrate culture, which resembled the initiation of metastasis.

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The impact of human milk oligosaccharides (HMO) on mucosal immunity, gut microbiota and response to rotavirus (RV) infection was investigated in the piglet model. Newborn piglets were fed with formula alone (FF) or formula supplemented with 4 g l(-1) HMO (HMO) or a prebiotic mixture of 9:1 short-chain galactooligosaccharides (3.6 g l(-1)) and long-chain fructooligosaccharides (0.

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Vegetative Filter Strips (VFS) have long been used to control the movement of agricultural nutrients and prevent them from reaching receiving waters. Earlier studies have shown that VFS also dramatically reduce both the kinetics and extent of Cryptosporidium parvum (C. parvum) oocysts overland transport.

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Human milk (HM) is rich in oligosaccharides (HMO) that exert prebiotic and anti-infective activities. HM feeding reduces the incidence of rotavirus (RV) infection in infants. Herein, the anti-RV activity of oligosaccharides was tested in an established in vitro system for assessing cellular binding and viral infectivity/replication, and also tested in a newly developed, acute RV infection, in situ piglet model.

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The role of collector surface charge heterogeneity on transport of Cryptosporidium parvum oocyst and carboxylate microsphere in 2-dimensional micromodels was studied. The cylindrical silica collectors within the micromodels were coated with 0, 10, 20, 50, and 100% Fe(2)O(3) patches. The experimental values of average removal efficiencies (η) of the Fe(2)O(3) patches and on the entire collectors were determined.

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Human colon carcinoma (HCT-8) cells show a stable transition from low to high metastatic state when cultured on appropriately soft substrates (21 kPa). Initially epithelial (E) in nature, the HCT-8 cells become rounded (R) after seven days of culture on soft substrate. R cells show a number of metastatic hallmarks [1].

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The microbial composition and in vitro fermentation characteristics of human milk oligosaccharides (HMO), lacto-N-neotetraose (LNnT), a 2:1 mixture of polydextrose (PDX) and galactooligosaccharides (GOS), and short-chain fructooligosaccharides (scFOS) by pooled ascending colonic microbiota from 9- and 17-d-old formula-fed (FF) and sow-reared (SR) piglets were assessed. pH change and gas, SCFA, and lactate production were determined after 0, 2, 4, 8, and 12 h of incubation. In most donor groups, the pH change was greater for scFOS fermentation and lower for PDX/GOS than for other substrates.

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Group A rotaviruses are a major cause of diarrhea in the young of many mammalian species. In rotavirus infected piglets mortality can be as high as 60%. Previous research in this laboratory has identified a porcine intestinal GM(3) ganglioside receptor that is required for sialic acid-dependent rotavirus recognition of host cells.

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Effective removal of Cryptosporidium parvum oocysts by granular filtration requires the knowledge of oocyst transport and deposition mechanisms, which can be obtained based on real time microscopic observation of oocyst transport in porous media. Attachment of oocysts to silica surface in a radial stagnation point flow cell and in a micromodel, which has 2-dimensional (2-D) microscopic pore structures consisting of an array of cylindrical collectors, was studied and compared. Real time transport of oocysts in the micromodel was recorded to determine the attached oocyst distributions in transversal and longitudinal directions.

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Pasteurella multocida toxin (PMT) is an AB toxin that causes pleiotropic effects in targeted host cells. The N-terminus of PMT (PMT-N) is considered to harbor the membrane receptor binding and translocation domains responsible for mediating cellular entry and delivery of the C-terminal catalytic domain into the host cytosol. Previous studies have implicated gangliosides as the host receptors for PMT binding.

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Cancer deaths are primarily caused by metastases, not by the parent tumor. During metastasis, malignant cells detach from the parent tumor, and spread through the circulatory system to invade new tissues and organs. The physical-chemical mechanisms and parameters within the cellular microenvironment that initiate the onset of metastasis, however, are not understood.

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We characterized the composition and conformation of Cryptosporidium parvum ( C. parvum ) oocyst wall surface macromolecules and studied their effect on interactions between C. parvum oocyst and quartz surface.

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A Radial Stagnation Point Flow (RSPF) system coupled with a microscope was used to study deposition of Cryptosporidium parvum oocysts on quartz and Suwannee River Natural Organic Matter (SRNOM)-coated surfaces in solutions with different Ca(2+) or Mg(2+) concentrations. Both untreated and proteinase K-treated oocysts were used. Deposition of oocysts on a SRNOM surface in Ca(2+) solution was higher than in Mg(2+) solution, even though the energy barriers calculated from Derjaguin-Landau-Verwey-Overbeek (DLVO) theory for Ca(2+) solution were higher than for Mg(2+) solution.

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Many studies have examined the long-term effects of selective logging on the abundance and diversity of free-ranging primates. Logging is known to reduce the abundance of some primate species through associated hunting and the loss of food trees for frugivores; however, the potential role of pathogens in such primate population declines is largely unexplored. Selective logging results in a suite of alterations in host ecology and forest structure that may alter pathogen dynamics in resident wildlife populations.

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Exponential expansion of human populations and human activities within primate habitats has resulted in high potential for pathogen exchange creating challenges for biodiversity conservation and global health. Under such conditions, resilient habitat generalists such as black and gold howler monkeys (Alouatta caraya) may act as effective sentinels to overall ecosystem health and alert us to impending epidemics in the human population. To better understand this potential, we examined noninvasively collected fecal samples from black and gold howler monkeys from remote, rural, and village populations in Northern Argentina.

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Soy protein-based infant formulas (SF) are commonly used to feed infants during their first year of life. SF contains isoflavones, which influence cell proliferation, but their actions in the developing intestine have received little attention. Herein, the impact of soy isoflavones and SF on intestinal development and rotavirus (RV) infectivity is described.

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Batch and flow-through experiments were conducted to investigate the removal and inactivation of rotavirus (RV) and bacteriophage MS2 using glass fiber coated with hematite nanoparticles. Batch tests showed a high removal of MS2 (2.49x10(11) plaque forming unit/g) and RV (8.

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Isoflavones and their related flavonoid compounds exert antiviral properties in vitro and in vivo against a wide range of viruses. Genistein is, by far, the most studied soy isoflavone in this regard, and it has been shown to inhibit the infectivity of enveloped or nonenveloped viruses, as well as single-stranded or double-stranded RNA or DNA viruses. At concentrations ranging from physiological to supraphysiological (3.

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A radial stagnation point flow (RSPF) system combined with a microscope was used to determine the deposition kinetics of Cryptosporidium parvum oocysts on quartz surfaces and silica surfaces coated with Suwannee River natural organic matter (SRNOM) in solutions with different ionic strengths. Microscopic evidence of C. parvum oocysts entrapped in the secondary minimum energy well was presented to show that among the entrapped C.

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