Schematic of the <i>LMNA</i> gene and lamin A protein indicating mutations.

<p>(A) Schematic of the <i>LMNA</i> gene and lamin A protein. Lamin A is encoded by exons 1–12, whereas lamin C terminates at exon 10 with six unique amino acids at its C-terminal. The alternative splice site for lamin A is indicated. Sequence variations affecting the splice donor or acceptor sites that lead to disease are shown for IVS-8. Missense mutations and deletions are indicated on the lamin A protein, where the head, central rod, and tail domain (incorporating the nuclear localization signal [NLS], and Ig-like fold) are indicated. Novel sequence variants are shown above the gene/protein. (B) Illustration of the evolutionary conservation of residues associated with novel missense mutations located in the coding region of <i>LMNA</i>. Sequences were obtained from the online database, Swiss-Prot (<a href="http://expasy.org/sprot/" target="_blank">http://expasy.org/sprot/</a>) and aligned using the Align online tool (<a href="http://www.uniprot.org/align/" target="_blank">http://www.uniprot.org/align/</a>).</p

Phenotype and genotype of patients.

<p>p.r.: Previously reported.</p><p>Phenotype and genotype of patients.</p

Muscle cell nuclear morphology.

<p>A, C, D: ×12000; B, E, F, G, H: ×25000. (A, B) Normal control. (C, D, G) Abnormal nuclear morphology. (C, D, F) Heterochromatin condensation (arrows). (E) Focal loss of nuclear membrane (arrows). (G) Nucleolar hole (arrows). (H) Accumulation of mitochondria around nucleus (arrows).</p

Clinical and neuroradiological findings of the patients.

<p>CK = creatine kinase; ECG = electrocardiogram; EMG = electromyogram; MRI = magnetic resonance imaging; UL = upper limb; LL = lower limb; ND = not done.</p><p>Clinical and neuroradiological findings of the patients.</p

Lamin A/C mislocation in mutant-transfected HEK 293 cells.

<p>Transfection was performed using (A) GFP, (B) pEGFP-N1-LMNA, (C) pEGFP-N1-LMNA-R48P, (D) pEGFP-N1-LMNA-R249W, (E) pEGFP-N1-LMNA-I373V, or (F) pEGFP-N1-LMNA-I497_E536del. Lamin A/C of the mutants (C–F) is distributed in clusters and is mislocated compared with that of the wild type (B).</p

Muscle biopsy specimens stained with hematoxylin and eosin.

<p>(A) Normal control (×200). (B) Specimen from patient 11 exhibiting inflammatory cellular infiltration with necrotic and regenerative fibers (×200). (C) Specimen from patient 15 exhibiting mild nuclear transfer and regenerative fibers (×400).</p

Saliva Microbiota Carry Caries-Specific Functional Gene Signatures

<div><p>Human saliva microbiota is phylogenetically divergent among host individuals yet their roles in health and disease are poorly appreciated. We employed a microbial functional gene microarray, HuMiChip 1.0, to reconstruct the global functional profiles of human saliva microbiota from ten healthy and ten caries-active adults. Saliva microbiota in the pilot population featured a vast diversity of functional genes. No significant distinction in gene number or diversity indices was observed between healthy and caries-active microbiota. However, co-presence network analysis of functional genes revealed that caries-active microbiota was more divergent in non-core genes than healthy microbiota, despite both groups exhibited a similar degree of conservation at their respective core genes. Furthermore, functional gene structure of saliva microbiota could potentially distinguish caries-active patients from healthy hosts. Microbial functions such as <i>Diaminopimelate epimerase</i>, <i>Prephenate dehydrogenase</i>, <i>Pyruvate-formate lyase</i> and <i>N-acetylmuramoyl-L-alanine amidase</i> were significantly linked to caries. Therefore, saliva microbiota carried disease-associated functional signatures, which could be potentially exploited for caries diagnosis.</p></div

Conservation of function genes encoded in saliva microbiota among human hosts.

<p>The <i>x</i>-axis stands for the number of saliva microbiota (i.e. hosts) included. The <i>y</i>-axis is the number of shared functional genes among the hosts, representing the means of 100 iterations. Error bars represent standard deviations.</p

Microbial functional markers that could potentially distinguish caries-active saliva microbiota from healthy ones.

<p>Each biomarker is a triplet-feature set of microbial genes.</p

Functional patterns of the ten healthy and ten caries-active human saliva microbiota.

<p>(<b>A</b>) Relative abundance of the functional genes among the 19 gene categories on HuMiChip 1.0. (<b>B</b>) Relative diversity of the functional genes among the 19 gene categories on HuMiChip 1.0.</p