BackgroundPlant nuclei superficially resemble animal and fungal nuclei, but the machinery and processes that underlie nuclear organization in these eukaryotic lineages appear to be evolutionarily distinct. Among the candidates for nuclear architectural elements in plants are coiled-coil proteins in the NMCP (Nuclear Matrix Constituent Protein) family. Using genetic and cytological approaches, we dissect the function of the four NMCP family proteins in Arabidopsis encoded by the CRWN genes, which were originally named LINC (LITTLE NUCLEI).ResultsCRWN proteins are essential for viability as evidenced by the inability to recover mutants that have disruptions in all four CRWN genes. Mutants deficient in different combinations of the four CRWN paralogs exhibit altered nuclear organization, including reduced nuclear size, aberrant nuclear shape and abnormal spatial organization of constitutive heterochromatin. Our results demonstrate functional diversification among CRWN paralogs; CRWN1 plays the predominant role in control of nuclear size and shape followed by CRWN4. Proper chromocenter organization is most sensitive to the deficiency of CRWN4. The reduction in nuclear volume in crwn mutants in the absence of a commensurate reduction in endoreduplication levels leads to an increase in average nuclear DNA density.ConclusionsOur findings indicate that CRWN proteins are important architectural components of plant nuclei that play diverse roles in both heterochromatin organization and the control of nuclear morphology.

DW imaging with b values of 0 and 800 sec/mm(2) allows sensitive and specific differentiation of clear cell, papillary, and chromophobic RCCs, suggesting that DW imaging may be useful in the preoperative characterization of RCC.

BackgroundTo determine whether MRI feature analysis can differentiate benign retroperitoneal extra-adrenal paragangliomas and schwannomas.MethodsThe MRI features of 50 patients with confirmed benign retroperitoneal extra-adrenal paragangliomas and schwannomas were retrospectively reviewed by two radiologists blinded to the histopathologic diagnosis. These features were compared between two types of tumours by use of the Mann-Whitney test and binary logistic regression. The patients’ clinical characteristics were reviewed.ResultsAnalysis of MRI images from 50 patients revealed no significant differences in the quantitative MRI features of lesion size, ratio of diameter and apparent diffusion coefficient. There were significant differences in the qualitative MRI features of location, necrosis, cysts and degree of tumour enhancement for two readers, with no significant differences in the other qualitative MRI features between these tumours. The combination of necrosis with degree of tumour enhancement during the arterial phase increased the probability that a retroperitoneal mass would represent retroperitoneal extra-adrenal paraganglioma as opposed to schwannoma.ConclusionWe have presented the largest series of MRI features of both benign retroperitoneal extra-adrenal paragangliomas and schwannomas. Some MRI features assist in the differentiation between these tumours, with imaging features consisting of necrosis and avid enhancement during the arterial phase, suggestive of retroperitoneal extra-adrenal paragangliomas.

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Recognition of drugs by immune cells is usually explained by the hapten model, which states that endogenous metabolites bind irreversibly to protein to stimulate immune cells. Synthetic metabolites interact directly with protein generating antigenic determinants for T-cells; however, experimental evidence relating intracellular metabolism in immune cells and the generation of physiologically relevant antigens to functional immune responses is lacking. The aim of this study was to develop an integrated approach using both animal and human experimental systems to characterize sulfamethoxazole (SMX) metabolism-derived antigenic protein adduct formation in immune cells and define the relationship between adduct formation, cell death, co-stimulatory signalling and stimulation of a T-cell response. Formation of SMX-derived adducts in antigen presenting cells was dose- and time-dependent, detectable at non-toxic concentrations and dependent on drug metabolizing enzyme activity. Adduct formation above a threshold induced necrotic cell death, dendritic cell co-stimulatory molecule expression and cytokine secretion. Antigen presenting cells cultured with SMX for 16h, the time needed for drug metabolism, stimulated T-cells from sensitized mice and lymphocytes and T-cell clones from allergic patients. Enzyme inhibition decreased SMX-derived protein adduct formation and the T-cell response. Dendritic cells cultured with SMX and adoptively transferred to recipient mice initiated an immune response; however, T-cells were stimulated with adducts derived from SMX metabolism in antigen presenting cells, not the parent drug. This study shows that antigen presenting cells metabolize SMX; subsequent protein binding generates a functional T-cell antigen. Adduct formation above a threshold stimulates cell death, which provides a maturation signal for dendritic cells.

The histone H3 N-terminal protein domain (N-tail) is regulated by multiple posttranslational modifications, including methylation, acetylation, phosphorylation, and by proteolytic cleavage. However, the mechanism underlying H3 N-tail proteolytic cleavage is largely elusive. Here, we report that JMJD5, a Jumonji C (JmjC) domain-containing protein, is a Cathepsin L-type protease that mediates histone H3 N-tail proteolytic cleavage under stress conditions that cause a DNA damage response. JMJD5 clips the H3 N-tail at the carboxyl side of monomethyl-lysine (Kme1) residues. H3 peptide digestion reveals that JMJD5 exclusively cleaves Kme1 H3 peptides, while little or no cleavage effect of JMJD5 on dimethyl-lysine (Kme2), trimethyl-lysine (Kme3), or unmethyl-lysine (Kme0) H3 peptides is observed. Although H3 Kme1 peptides of K4, K9, K27, and K36 can all be cleaved by JMJD5, K9 of H3 is the major cleavage site , and H3.3 is the major H3 target of JMJD5 cleavage. Cleavage is enhanced at gene promoters bound and repressed by JMJD5 suggesting a role for H3 N-tail cleavage in gene expression regulation.

Acupuncture has been a popular alternative medicine in the United States for several decades. Its therapeutic effects on pain have been validated by both basic and clinical researches, and it is currently emerging as a unique non-pharmaceutical choice for pain against opioid crisis. However, the full spectrum of acupuncture indications remains unexplored. In this study, we conducted a cross-sectional survey among 419 acupuncturists nation-wide to investigate the top 10 and top 99 acupuncture indications in private clinics in the United States. We found the top 10 indications to be: lower back pain, depression, anxiety, headache, arthritis, allergies, general pain, female infertility, insomnia, neck pain and frozen shoulder. Among the top 99 indications, pain represents the largest category; and mental health management, especially for mood disorders, is in greatest demand. The following popular groups are: immune system dysfunctions, gastrointestinal diseases, gynecology and neurology. In addition, specialty index, commonality index, and the potential to become medical specialties were estimated for each indication. Demographic analysis suggests that China trained acupuncturists tend to have broader indication spectrums, but the top conditions treated are primarily decided by local needs. Also, gender, resident states, age and clinical experience all affect indication distributions. Our data for the first time outlines the profile of acupuncture treatable conditions in the US and is valuable for strategic planning in acupuncture training, healthcare administration and public education.

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