Possible evolution of splice-junction signals in eukaryotic genes from stop codons.

Splice-junction sequence signals are strongly conserved structural components of eukaryotic genes. These sequences border exon/intron junctions and aid in the process of removing introns by the RNA splicing machinery. Although substantial research has been undertaken to understand the mechanism of splicing, little is known about the origin and evolution of these splice signal sequences. Based on the previously published theory that the primitive genes evolved in pieces from primordial genetic sequences to avoid the interfering stop codons, a "stop-codon walk" mechanism is proposed in this paper to have assisted in the evolution of coding genes. This mechanism predicts the presence of stop codons in splice-junction signals inside the introns. Evidence of the consistent presence of stop codons in the splice-junction signals, in a position where they are expected, is shown by the analysis of codon statistics in these signal sequences in the GenBank databank. The results suggest that the splice-junction signals may have evolved from stop codons as a consequence of a selective pressure to avoid stop codons during the original evolution of coding genes. They also suggest that other splice signals within the introns, such as the branch-point sequence, may have evolved from stop codons for similar reasons.     

The reimagination of sustainable integrated care in Ontario,Canada

Purpose/settingTo encourage clinical and financial efficiency, the Canadian province of Ontario initiated an integrated care program – Integrated Funding Models (IFMs) that required collaboration and coordination across acute and post-acute care sectors. This research shows how program implementers went beyond policy-makers’ original designs, to make integrated care sustainable for chronic diseases.MethodsForty-five interviews were conducted with program participants at three chronic disease programs, as well as with policymakers. Interviews were conducted over two phases; during early implementation in 2016, and as programs matured in 2018. Data were analyzed through a cultural constructivist lens to understand how participants shaped programs.FindingsParticipants desired greater accountability and control. Participants in the first program wanted localized control over decision-making. In the second, participants initiated greater control over financial uncertainty. In the third program, hospital participants sought greater control over community care. Participants across programs simultaneously wanted integrated care to be expanded holistically, spatially, and temporally for patients, extending the length of care, and expanding the spaces in which care was provided. Findings also suggest a gap between program implementers’ and policymakers’ conceptualizations of integrated care.ConclusionThis work shows how IFMs were reimagined in ways that transcended their original conceptualization as spatially and temporally delimited initiatives aimed at improving coordination and efficiency. It has practical implications for those facing sustainability challenges in other contexts.     

Molecular Characterization of 2-Chlorobiphenyl Degrading Stenotrophomonas maltophilia GS-103

The catabolic potential of transformer oil contaminated soil bacteria in aerobic degradation of polychlorinated biphenyls (PCB) were assessed. Transformer oil contaminated soil sample was subjected to microcosm enrichment experiments (PAS medium/biphenyl as sole carbon source). PCB-degrading activity of the enrichment cultures in PAS medium with the addition of 2-chlorobiphenyl were analysed by GC–MS indicated that, although the isolates differed in PCB-degrading capabilities, all of the enrichment cultures expressed activity toward at least some of the lower chlorinated congeners. Biphenyl-utilizing bacteria isolated from the most active PCB-degrading mixed cultures showed little taxonomic diversity and identified as Stenotrophomonas maltophilia GS-103.     

Prevalence of peripheral neuropathy among type 2 diabetes mellitus patients in a rural health centre in South India

International Journal of Diabetes in Developing Countries - There is a huge burden of diabetes-related complications, both microvascular and macrovascular, in India. With the rising prevalence of...     

Functional Impression Technique for an Ocular Prosthesis

The loss of an eye is the most devastating, psychologically damaging experience for a patient. All hope to bring such patients back to their accustomed and comfortable life-style rests on a cosmetically acceptable prosthesis. An intra-orbital ocular prosthesis serves the purpose in those defects where the orbital margins are intact. Though the stock eye may match the natural eye’s iris and sclera in color, the fit of the prosthesis to the tissue bed may not be as good as desired. Herein, a functional ocular impression technique is presented to achieve a better fit of the prosthesis to the defect area. This technique aims to combine cosmetic excellence with comfort for greater benefit to the patient.     

The spatial relationship between neurons and astrocytes in HIV-associated dementia

Specific neuronal spatial distributional patterns have previously been correlated with increasing severity of HIV-associated dementia (HAD). As astrocytes are also a putative site of neurotoxicity, we investigated the spatial relationships of astrocytes with pyramidal and interneurons in the superior frontal gyrus from 29 patients who died from acquired immunodeficiency syndrome. Frontal cortical brain tissue was taken from diseased HIV patients who had been assessed for the presence and severity of HAD using the Memorial Sloan-Kettering Scale. No correlation was found between neuronal density and severity of dementia. However, the pattern of astrocytes became more clustered as dementia progressed. Bivariate spatial pattern analysis of neuronal populations with astrocytes revealed that, with increasing dementia severity, astrocytes and large pyramidal neurons increasingly “repelled” each other, while astrocytes and interneurons evidenced increasing “attraction.” This implies that astrocytes may be more likely to be situated in the vicinity of surviving interneurons but less likely to be situated near surviving large pyramidal neurons in the setting of progressing HAD.     

Characterization of Gene Therapy Associated Uveitis Following Intravitreal Adeno-Associated Virus Injection in Mice

PurposeTo characterize the intraocular immune cell infiltrate induced by intravitreal adeno-associated virus (AAV) gene therapy.MethodsAAV vectors carrying plasmids expressing green fluorescent protein under the control of PR2.1 were injected intravitreally into AAV naive and AAV primed C57Bl/6 mice. Clinical inflammation was assessed using optical coherence tomography. Intraocular immune cell populations were identified and quantified by flow cytometry on days 1, 7, and 29 after intravitreal injection and compared with sham and fellow eye controls.ResultsOptical coherence tomography inflammation score and total CD45+ cell number were significantly higher in AAV injected eyes compared to uninjected fellow eye and sham injected controls. Clinically apparent inflammation (vitritis on optical coherence tomography) and cellular inflammation (CD45+ cell number) was significantly increased in AAV injected eyes and peaked around day 7. Vitritis resolved by day 29, but cellular inflammation persisted through day 29. On day 1, neutrophils and activated monocytes were the dominant cell populations in all AAV injected eyes. On day 7, eyes of AAV exposed animals had significantly more dendritic cells and T cells than eyes of AAV naive animals. By day 29, CD8– T cells were the dominant CD45+ cell population in AAV injected eyes.ConclusionsIntravitreal AAV injection in mice generates clinically evident inflammation that is mild and seems to resolve spontaneously. However, the total number of intraocular CD45+ cells, particularly T cells, remain elevated. Both innate and adaptive immune cells respond to intravitreal AAV regardless of prior immune status, but the adaptive response is delayed in AAV naive eyes.