The microRNAs of Caenorhabditis elegans Lim, Lee P; Lau, Nelson C; Weinstein, Earl G ...
Genes & development,
2003-Apr-15, 2003-04-15, 20030415, Letnik:
17, Številka:
8
Journal Article
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MicroRNAs (miRNAs) are an abundant class of tiny RNAs thought to regulate the expression of protein-coding genes in plants and animals. In the present study, we describe a computational procedure to ...identify miRNA genes conserved in more than one genome. Applying this program, known as MiRscan, together with molecular identification and validation methods, we have identified most of the miRNA genes in the nematode Caenorhabditis elegans. The total number of validated miRNA genes stands at 88, with no more than 35 genes remaining to be detected or validated. These 88 miRNA genes represent 48 gene families; 46 of these families (comprising 86 of the 88 genes) are conserved in Caenorhabditis briggsae, and 22 families are conserved in humans. More than a third of the worm miRNAs, including newly identified members of the lin-4 and let-7 gene families, are differentially expressed during larval development, suggesting a role for these miRNAs in mediating larval developmental transitions. Most are present at very high steady-state levels-more than 1000 molecules per cell, with some exceeding 50,000 molecules per cell. Our census of the worm miRNAs and their expression patterns helps define this class of noncoding RNAs, lays the groundwork for functional studies, and provides the tools for more comprehensive analyses of miRNA genes in other species.
Enterococci are gut microbes of most land animals. Likely appearing first in the guts of arthropods as they moved onto land, they diversified over hundreds of millions of years adapting to evolving ...hosts and host diets. Over 60 enterococcal species are now known. Two species,
and
are common constituents of the human microbiome. They are also now leading causes of multidrug-resistant hospital-associated infection. The basis for host association of enterococcal species is unknown. To begin identifying traits that drive host association, we collected 886 enterococcal strains from widely diverse hosts, ecologies, and geographies. This identified 18 previously undescribed species expanding genus diversity by >25%. These species harbor diverse genes including toxins and systems for detoxification and resource acquisition.
and
were isolated from diverse hosts highlighting their generalist properties. Most other species showed a more restricted distribution indicative of specialized host association. The expanded species diversity permitted the
genus phylogeny to be viewed with unprecedented resolution, allowing features to be identified that distinguish its four deeply rooted clades, and the entry of genes associated with range expansion such as B-vitamin biosynthesis and flagellar motility to be mapped to the phylogeny. This work provides an unprecedentedly broad and deep view of the genus
, including insights into its evolution, potential new threats to human health, and where substantial additional enterococcal diversity is likely to be found.
The acyclic nucleoside phosphonate cidofovir (CDV) and its closely related analogue (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)-adenine (S-HPMPA) have been reported to have activity against many ...adenovirus (AdV) serotypes. A new series of orally active ether lipid-ester prodrugs of CDV and of (S)-HPMPA that have slight differences in the structure of their lipid esters were evaluated, in tissue-culture cells, for activity against 5 AdV serotypes. The results indicated that, against several AdV serotypes, the most active compounds were 15-2500-fold more active than the unmodified parent compounds and should be evaluated further for their potential to treat AdV infections in humans.
Many chemicals released into the environment display estrogenic activity including the oral contraceptive ethinyl estradiol (EE2) and the plastic monomer bisphenol A (BPA). EE2 is present in some ...aquatic systems at concentrations sufficient to alter reproductive function of fishes. Many concerns have been raised about the potential effects of BPA. The National Toxicology Program rated the potential effects of low doses of BPA on behavior and central nervous system (CNS) as an area of “some concern,” whereas most effects were rated as of “negligible” or “minimal” concern. However, the number of robust studies in this area was limited. The current study was designed to determine if maternal exposure to relatively low oral doses of EE2 or BPA in utero and during lactation would alter the expression of well-characterized sexually dimorphic behaviors or alter the age of puberty or reproductive function in the female Long-Evans rat offspring. Pregnant rats were gavaged with vehicle, EE2 (0.05–50 μg/kg/day), or BPA (2, 20, and 200 μg/kg/day) from day 7 of gestation to postnatal day (PND) 18, and the female offspring were studied. EE2 (50 μg/kg/day) increased anogenital distance and reduced pup body weight at PND2, accelerated the age at vaginal opening, reduced F1 fertility and F2 litter sizes, and induced malformations of the external genitalia (5 μg/kg). F1 females exposed to EE2 also displayed a reduced (male-like) saccharin preference (5 μg/kg) and absence of lordosis behavior (15 μg/kg), indications of defeminization of the CNS. BPA had no effect on any of the aforementioned measures. These results demonstrate that developmental exposure to pharmacologically relevant dosage levels of EE2 can permanently disrupt the reproductive morphology and function of the female rat.
In this work, the ultraviolet light-emitting diodes (UV-LEDs) at 380nm were grown on patterned sapphire substrate (PSS) by atmospheric pressure metal organic chemical vapor deposition (AP-MOCVD). A ...sputtered AlN nucleation layer was utilized on the PSS to enhance the quality of the epitaxial layer. By using high-resolution X-ray diffraction, the full-width at half-maximum of the rocking curve shows that the UV-LEDs with sputtered AlN nucleation layer had better crystalline quality when compared to conventional GaN nucleation samples. From the scanning electron microscope (SEM) and transmission electron microscopy (TEM) images, it can be observed that the tip and sidewall portion of the pattern was smooth using the sputtered AlN nucleation layer. The threading dislocation densities (TDDs) are reduced from 6×107cm−2 to 2.5×107cm−2 at the interface between the u-GaN layers for conventional and AlN PSS devices, respectively. As a result, a much higher light output power was achieved. The light output power at an injection current of 20mA was enhanced by 30%. Further photoluminescence (PL) measurement and numerical simulation confirm that this increase of output power can be attributed to the improvement of material quality and light extraction.
•We investigate the UV-LEDs on PSS at 380nm were grown by the AP-MOCVD.•The sputtered AlN nucleation layer was utilized on the PSS to enhance the quality of the epitaxial layer.•The UV-LEDs with sputtered AlN nucleation layer is higher light output power compared with GaN nucleation layer.
Microduplications of the Sotos syndrome region containing NSD1 on 5q35 have recently been proposed to cause a syndrome of microcephaly, short stature and developmental delay. To further characterize ...this emerging syndrome, we report the clinical details of 12 individuals from 8 families found to have interstitial duplications involving NSD1, ranging in size from 370 kb to 3.7 Mb. All individuals are microcephalic, and height and childhood weight range from below average to severely restricted. Mild-to-moderate learning disabilities and/or developmental delay are present in all individuals, including carrier family members of probands; dysmorphic features and digital anomalies are present in a majority. Craniosynostosis is present in the individual with the largest duplication, though the duplication does not include MSX2, mutations of which can cause craniosynostosis, on 5q35.2. A comparison of the smallest duplication in our cohort that includes the entire NSD1 gene to the individual with the largest duplication that only partially overlaps NSD1 suggests that whole-gene duplication of NSD1 in and of itself may be sufficient to cause the abnormal growth parameters seen in these patients. NSD1 duplications may therefore be added to a growing list of copy number variations for which deletion and duplication of specific genes have contrasting effects on body development.
Objectives. Clinical care and therapeutic trials in idiopathic inflammatory myopathies (IIM) require accurate and consistent assessment of cutaneous involvement. The Cutaneous Assessment Tool (CAT) ...was designed to measure skin activity and damage in IIM. We describe the development and inter-rater reliability of the CAT, and the frequency of lesions endorsed in a large population of juvenile IIM patients. Methods. The CAT includes 10 activity, 4 damage and 7 combined lesions. Thirty-two photographic slides depicting IIM skin lesions were assessed by 11 raters. One hundred and twenty-three children were assessed by 11 paediatric rheumatologists at 10 centres. Inter-rater reliability was assessed using simple agreements and intra-class correlation coefficients (ICC). Results. Simple agreements in recognizing lesions as present or absent were generally high (0.5–1.0). ICCs for CAT lesions were moderate (0.4–0.75) in both slides and real patients. ICCs for the CAT activity and damage scores were 0.71 and 0.81, respectively. CAT activity scores ranged from 0 to 44 (median 7, potential range 0–96) and CAT damage scores ranged from 0 to 13 (median 1, potential range 0–22). The most common cutaneous lesions endorsed were periungual capillary loop changes (63%), Gottron's papules/sign (53%), heliotrope rash (49%) and malar/facial erythema (49%). Conclusions. Total CAT activity and damage scores have moderate to good reliability. Assessors generally agree on the presence of a variety of cutaneous lesions. The CAT is a promising, semi-quantitative tool to comprehensively assess skin disease activity and damage in IIM.
The interferon-inducible, double-stranded RNA-dependent protein kinase PKR has been implicated in anti-viral, anti-tumor,
and apoptotic responses. Others have attempted to examine the requirement of ...PKR in these roles by targeted disruption at
the amino terminal-encoding region of the Pkr gene. By using a strategy that aims at disruption of the catalytic domain of PKR, we have generated mice that are genetically
ablated for functional PKR. Similar to the other mouse model of Pkr disruption, we have observed no consequences of loss of PKR on tumor suppression. Anti-viral response to influenza and vaccinia
also appeared to be normal in mice and in cells lacking PKR. Cytokine signaling in the type I interferon pathway is normal
but may be compromised in the erythropoietin pathway in erythroid bone marrow precursors. Contrary to the amino-terminal targeted
Pkr mouse, tumor necrosis factor α-induced apoptosis and the anti-viral apoptosis response to influenza is not impaired in catalytic
domain-targeted Pkr -null cells. The observation of intact eukaryotic initiation factor-2α phosphorylation in these Pkr -null cells provides proof of rescue by another eukaryotic initiation factor-2α kinase(s).
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