Innate immunity glycoprotein gp-340 variants may modulate human susceptibility to dental caries

<p>Abstract</p> <p>Background</p> <p>Bacterial adhesion is an important determinant of colonization and infection, including dental caries. The salivary scavenger receptor cysteine-rich glycoprotein gp-340, which mediates adhesion of <it>Streptococcus mutans </it>(implicated in caries), harbours three major size variants, designated gp-340 I to III, each specific to an individual saliva. Here we have examined the association of the gp-340 I to III polymorphisms with caries experience and adhesion of <it>S. mutans</it>.</p> <p>Methods</p> <p>A case-referent study was performed in 12-year-old Swedish children with high (n = 19) or low (n = 19) caries experiences. We measured the gp-340 I to III saliva phenotypes and correlated those with multiple outcome measures for caries experience and saliva adhesion of <it>S. mutans </it>using the partial least squares (PLS) multivariate projection technique. In addition, we used traditional statistics and 2-year caries increment to verify the established PLS associations, and bacterial adhesion to purified gp-340 I to III proteins to support possible mechanisms.</p> <p>Results</p> <p>All except one subject were typed as gp-340 I to III (10, 23 and 4, respectively). The gp-340 I phenotype correlated positively with caries experience (VIP = 1.37) and saliva adhesion of <it>S. mutans </it>Ingbritt (VIP = 1.47). The gp-340 II and III phenotypes tended to behave in the opposite way. Moreover, the gp-340 I phenotype tended to show an increased 2-year caries increment compared to phenotypes II/III. Purified gp-340 I protein mediated markedly higher adhesion of <it>S. mutans </it>strains Ingbritt and NG8 and <it>Lactococcus lactis </it>expressing AgI/II adhesins (SpaP or PAc) compared to gp-340 II and III proteins. In addition, the gp-340 I protein appeared over represented in subjects positive for Db, an allelic acidic PRP variant associated with caries, and subjects positive for both gp-340 I and Db tended to experience more caries than those negative for both proteins.</p> <p>Conclusion</p> <p>Gp-340 I behaves as a caries susceptibility protein.</p

Long-term associative learning predicts verbal short-term memory performance

Studies using tests such as digit span and nonword repetition have implicated short-term memory across a range of developmental domains. Such tests ostensibly assess specialized processes for the short-term manipulation and maintenance of information that are often argued to enable long-term learning. However, there is considerable evidence for an influence of long-term linguistic learning on performance in short-term memory tasks that brings into question the role of a specialized short-term memory system separate from long-term knowledge. Using natural language corpora, we show experimentally and computationally that performance on three widely used measures of short-term memory (digit span, nonword repetition, and sentence recall) can be predicted from simple associative learning operating on the linguistic environment to which a typical child may have been exposed. The findings support the broad view that short-term verbal memory performance reflects the application of long-term language knowledge to the experimental setting

Influence of soil type and natural Zn chelates on flax response, tensile properties and soil Zn availability

A greenhouse experiment was conducted on weakly acidic and calcareous soils to evaluate the relative efficiencies of three natural Zn chelates [Zn-aminelignosulphonate (Zn-AML), Zn-polyhydroxyphenylcarboxylate (Zn-PHP) and Zn-S,S-ethylenediaminedisuccinate (Zn-S,S-EDDS)] applied to a crop textile flax (Linum ussitatisimum L.) at application rates of 0, 5 and 10 mg Zn kg−1. In the flax plant, the following parameters were determined: dry matter yield, soluble and total Zn concentrations in leaf and stem, chlorophyll, crude fibre, and tensile properties. For the different soil samples, the following parameters were determined: available Zn (DTPA-AB and Mehlich-3 extractable Zn), easily leachable Zn (BaCl2-extractable Zn), the distribution of Zn fractions, pH and redox potential. On the basis of the use of added Zn by flax, or Zn utilization, it would seem recommendable to apply Zn-S,S-EDDS at the low Zn rate in both soils. In contrast, adding the high Zn rate of this chelate to the weakly acidic soil produced an excessive Zn concentration in the plant, which caused a significant decrease in both dry matter yield and chlorophyll content. Furthermore, assessing available Zn with the DTPA-AB method proved the best way of estimating the level of excess Zn in flax plants. The soluble Zn concentration, which was established with 2-(N-morpholino)ethanesulfonic acid reagent (MES), of plant fresh and dry matter could be used as an alternative way of diagnosing the nutritional status of Zn in flax plants. In this experiment, the highest soil pHs were associated with the lowest redox potentials, which coincided with the smallest amounts of available Zn and water soluble Zn in soil, and the lowest levels of Zn uptake by flax plants

Localized induction of gene expression in embryonic stem cell aggregates using holographic optical tweezers to create biochemical gradients

Three-dimensional (3D) cell models that mimic the structure and function of native tissues are enabling more detailed study of physiological and pathological mechanisms in vitro. We have previously demonstrated the ability to build and manipulate 3D multicellular microscopic structures using holographic optical tweezers (HOTs). Here, we show the construction of a precisely patterned 3D microenvironment and biochemical gradient model consisting of mouse embryoid bodies (mEBs) and polymer microparticles loaded with retinoic acid (RA), embedded in a hydrogel. We demonstrate discrete, zonal expression of the RA-inducible protein Stra8 within mEBs in response to release of RA from polymer microparticles, corresponding directly to the defined 3D positioning of the microparticles using HOTs. These results demonstrate the ability of this technology to create chemical microgradients at definable length scales and to elicit, with fidelity and precision, specific biological responses. This technique can be used in the study of in vitro microenvironments to enable new insights on 3D cell models, their cellular assembly, and the delivery of drug or biochemical molecules for engineering and interrogation of functional and morphogenic responses

Correction: Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK 'Alert Level 4' phase of the B-MaP-C study.

A Correction to this paper has been published: https://doi.org/10.1038/s41416-021-01378-

Barriers to Non-Viral Vector-Mediated Gene Delivery in the Nervous System

Efficient methods for cell line transfection are well described, but, for primary neurons, a high-yield method different from those relying on viral vectors is lacking. Viral transfection has several drawbacks, such as the complexity of vector preparation, safety concerns, and the generation of immune and inflammatory responses when used in vivo. However, one of the main problems for the use of non-viral gene vectors for neuronal transfection is their low efficiency when compared with viral vectors. Transgene expression, or siRNA delivery mediated by non-viral vectors, is the result of multiple processes related to cellular membrane crossing, intracellular traffic, and/or nuclear delivery of the genetic material cargo. This review will deal with the barriers that different nanoparticles (cationic lipids, polyethyleneimine, dendrimers and carbon nanotubes) must overcome to efficiently deliver their cargo to central nervous system cells, including internalization into the neurons, interaction with intracellular organelles such as lysosomes, and transport across the nuclear membrane of the neuron in the case of DNA transfection. Furthermore, when used in vivo, the nanoparticles should efficiently cross the blood-brain barrier to reach the target cells in the brain