A modified Oster-Murray-Harris mechanical model of morphogenesis

There are two main modeling paradigms for biological pattern formation in developmental biology: chemical prepattern models and cell aggregation models. This paper focuses on an example of a cell aggregation model, the mechanical model developed by Oster, Murray, and Harris [Development, 78 (1983), pp. 83--125]. We revisit the Oster--Murray--Harris model and find that, due to the infinitesimal displacement assumption made in the original version of this model, there is a restriction on the types of boundary conditions that can be prescribed. We derive a modified form of the model which relaxes the infinitesimal displacement assumption. We analyze the dynamics of this model using linear and multiscale nonlinear analysis and show that it has the same linear behavior as the original Oster--Murray--Harris model. Nonlinear analysis, however, predicts that the modified model will allow for a wider range of parameters where the solution evolves to a bounded steady state. The results from both analyses are verified through numerical simulations of the full nonlinear model in one and two dimensions. The increased range of boundary conditions that are well-posed, as well as a wider range of parameters that yield bounded steady states, renders the modified model more applicable to, and more robust for, comparisons with experiments

Village Water Ozonation System

The Village Water Ozonation System (VWOS) team’s core mission statement is to provide economically sustainable and culturally sensitive drinking water solutions for communities, to empower communities with the ability to properly maintain their drinking water supply, and to transform people’s lives by decreasing the occurrences of waterborne diseases. Currently, the VWOS team is partnering with Friends in Action to design and implement two drinking water treatment systems for the community living on Rama Cay, an island in the Bluefields Lagoon on the eastern coastline of Nicaragua. The wells on the island are contaminated with E. coli and other bacteria and contain high levels of salt that cause the water to be unhealthy, distasteful, and corrosive to metal equipment in the system. The team hopes to design a system that will disinfect the water, remove salinity from the well water with a safe and efficient disposal of all byproducts, and decrease corrosion agents. VWOS is partnering with Forward Edge International for the third time (Nicaragua 2009 and Mexico 2016) to design water treatment systems for communities in Oaxaca, Mexico and Kijabe, Kenya. The system for Oaxaca is ready for implementation and awaits availability to travel. The system for Kijabe is in the initial stage of communicating with the client on specifics for the design.https://mosaic.messiah.edu/engr2021/1018/thumbnail.jp

Loss of TRP53 (p53) accelerates tumorigenesis and changes the tumor spectrum of SJL/J mice.

Known as the guardian of the genome, transformation-related protein 53 (TRP53) is a well -known tumor suppressor. Here, we describe a novel TRP53 deficient mouse model on a tumor prone background-SJL/J mice. The absence of TRP53 (TRP53 nullizygosity) leads to a shift in the tumor spectrum from a non-Hodgkin\u27s-like disease to thymic lymphomas and testicular teratomas at a very rapid tumor onset averaging ~12 weeks of age. In haplotype studies, comparing tumor prone versus tumor resistant Trp53 null mouse strains, we found that other tumor suppressor, DNA repair and/or immune system genes modulate tumor incidence in TRP53 null strains, suggesting that even a strong tumor suppressor such as TRP53 is modulated by genetic background. Due to their rapid development of tumors, the SJL/J TRP53 null mice generated here can be used as an efficient chemotherapy or immunotherapy screening mouse model

Inhibition of CCL3 abrogated precursor cell fusion and bone erosions in human osteoclast cultures and murine collagen-induced arthritis

Objective Macrophage inflammatory protein 1-alpha (CCL3) is a chemokine that regulates macrophage trafficking to the inflamed joint. The agonistic effect of CCL3 on osteolytic lesions in patients with multiple myeloma is recognized; however, its role in skeletal damage during inflammatory arthritis has not been established. The aim of the study was to explore the role of osteoclast-associated CCL3 upon bone resorption, and to test its pharmacological blockade for protecting against bone pathology during inflammatory arthritis. Methods CCL3 production was studied during osteoclast differentiation from osteoclast precursor cells: human CD14-positive mononuclear cells. Mice with CIA were treated with an anti-CCL3 antibody. The effect of CCL3 blockade through mAb was studied through osteoclast number, cytokine production and bone resorption on ivory disks, and in vivo through CIA progression (clinical score, paw diameter, synovial inflammation and bone damage). Results Over time, CCL3 increased in parallel with the number of osteoclasts in culture. Anti-CCL3 treatment achieved a concentration-dependent inhibition of osteoclast fusion and reduced pit formation on ivory disks (P ⩽ 0.05). In CIA, anti-CCL3 treatment reduced joint damage and significantly decreased multinucleated tartrate-resistant acid phosphatase-positive osteoclasts and erosions in the wrists (P < 0.05) and elbows (P < 0.05), while also reducing joint erosions in the hind (P < 0.01) and fore paws (P < 0.01) as confirmed by X-ray. Conclusion Inhibition of osteoclast-associated CCL3 reduced osteoclast formation and function whilst attenuating arthritis-associated bone loss and controlling development of erosion in murine joints, thus uncoupling bone damage from inflammation. Our findings may help future innovations for the diagnosis and treatment of inflammatory arthritis

Animals can assign novel odours to a known category

The ability to identify a novel stimulus as a member of a known category allows an organism torespond appropriately towards it. Categorisation is thus a fundamental component of cognition andan essential tool for processing and responding to unknown stimuli. Therefore, one might expectto observe it throughout the animal kingdom and across sensory domains. There is much evidenceof visual categorisation in non-human animals, but we currently know little about this process inother modalities. In this experiment, we investigated categorisation in the olfactory domain. Dogswere trained to discriminate between 40 odours; the presence or absence of accelerants formed thecategorical rule. Those in the experimental group were rewarded for responding to substrates withaccelerants (either burnt or un-burnt) and inhibit responses to the same substrates (either burnt or unburnt)without accelerants (S+ counterbalanced). The pseudocategory control group was trained onthe same stimuli without the categorical rule. The experimental group learned the discrimination andanimals were able to generalise to novel stimuli from the same category. None of the control animalswere able to learn the discrimination within the maximum number of trials. This study provides the firstevidence that non-human animals can learn to categorise non-biologically relevant odour information

NPC1 deficiency impairs cerebellar postnatal development of microglia and climbing fiber refinement in a mouse model of Niemann-Pick disease type C.

Little is known about the effects of NPC1 deficiency in brain development and whether these effects contribute to neurodegeneration in Niemann-Pick disease type C (NPC). Degeneration of cerebellar Purkinje cells occurs at an earlier stage and to a greater extent in NPC; therefore, we analyzed the effect of NPC1 deficiency on microglia and on climbing fiber synaptic refinement during cerebellar postnatal development using th

The Metabochip, a Custom Genotyping Array for Genetic Studies of Metabolic, Cardiovascular, and Anthropometric Traits

PMCID: PMC3410907This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Dietary t10,c12-CLA but not c9,t11 CLA Reduces Adipocyte Size in the Absence of Changes in the Adipose Renin–Angiotensin System in fa/fa Zucker Rats

In obesity, increased activity of the local renin–angiotensin system (RAS) and enlarged adipocytes with altered adipokine production are linked to the development of obesity-related health problems and cardiovascular disease. Mixtures of conjugated linoleic acid (CLA) isomers have been shown to reduce adipocyte size and alter the production of adipokines. The objective of this study was to investigate the effects of feeding individual CLA isomers on adipocyte size and adipokines associated with the local adipose RAS. Male fa/fa Zucker rats received either (a) control, (b) cis(c)9,trans(t)11-CLA, or (c) t10,c12-CLA diet for 8 weeks. The t10,c12-CLA isomer reduced adipocyte size and increased cell number in epididymal adipose tissue. RT-PCR and Western blot analysis revealed that neither CLA isomer altered mRNA or protein levels of angiotensinogen or AngII receptors in adipose tissue. Likewise, levels of the pro-inflammatory cytokines TNF-α and IL-6 or the anti-inflammatory cytokine IL-10 were unchanged in adipose tissue. Similarly, neither CLA isomer had any effect on phosphorylation nor DNA binding of NF-κB. Our results suggest that although the t10,c12-CLA isomer had beneficial effects on reducing adipocyte size in obese rats, this did not translate into changes in the local adipose RAS or associated adipokines