The annotation of the mammalian protein-coding genome is incomplete. Arbitrary size restriction of open reading frames (ORFs) and the absolute requirement for a methionine codon as the sole initiator ...of translation have constrained the identification of potentially important transcripts with non-canonical protein-coding potential
. Here, using unbiased transcriptomic approaches in macrophages that respond to bacterial infection, we show that ribosomes associate with a large number of RNAs that were previously annotated as 'non-protein coding'. Although the idea that such non-canonical ORFs can encode functional proteins is controversial
, we identify a range of short and non-ATG-initiated ORFs that can generate stable and spatially distinct proteins. Notably, we show that the translation of a new ORF 'hidden' within the long non-coding RNA Aw112010 is essential for the orchestration of mucosal immunity during both bacterial infection and colitis. This work expands our interpretation of the protein-coding genome and demonstrates that proteinaceous products generated from non-canonical ORFs are crucial for the immune response in vivo. We therefore propose that the misannotation of non-canonical ORF-containing genes as non-coding RNAs may obscure the essential role of a multitude of previously undiscovered protein-coding genes in immunity and disease.
Maximum power point tracking (MPPT) is important in photovoltaic systems for effective solar energy harvesting. One of the most popular MPPT techniques is the widely adapted perturb and observe (P&O) ...method owing to its simple and low-cost implementation. The downside is that the steady-state performance is compromised by the inherent perturbation. The magnitude of the steady-state oscillation can be lessened by reducing the perturbation size. However, the approach slows down the tracking speed during rapidly changing atmospheric conditions. Thus, the selection of perturbation value becomes difficult since it always involves the tradeoff between the tracking speed and steady-state ripple. This paper proposes a novel start-stop mechanism to eliminate the compromise of the traditional P&O MPPT method. Thanks to the advantages of simplicity and ease of implementation, the mechanism targets the MPPT solution for submodule integrated converters, which demand for a low-cost solution. The experimental evaluation of the proposed algorithm is compared with the benchmark P&O algorithm showing the claimed advantages.
S2573 Not Every Rectal Cancer Is Adenocarcinoma Baqir, Syed Mujtaba; Kaur, Avleen; Lu, Tiffany ...
The American journal of gastroenterology,
10/2023, Letnik:
118, Številka:
10S
Journal Article
Sepsis remains one of the leading causes of death in burn patients who survive the initial insult of injury. Disruption of the intestinal epithelial barrier has been shown after burn injury; this can ...lead to the translocation of bacteria or their products (e.g., endotoxin) from the intestinal lumen to the circulation, thereby increasing the risk for sepsis in immunocompromised individuals. Since the maintenance of the epithelial barrier is largely dependent on the intestinal microbiota, we examined the diversity of the intestinal microbiome of severely burned patients and a controlled mouse model of burn injury. We show that burn injury induces a dramatic dysbiosis of the intestinal microbiome of both humans and mice and allows for similar overgrowths of Gram-negative aerobic bacteria. Furthermore, we show that the bacteria increasing in abundance have the potential to translocate to extra-intestinal sites. This study provides an insight into how the diversity of the intestinal microbiome changes after burn injury and some of the consequences these gut bacteria can have in the host.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Enlarged perivascular spaces (ePVS) are difficult to quantify, and their etiologies and consequences are poorly understood. Vanderbilt Memory and Aging Project participants (n = 327, 73 ± 7 years) ...completed 3T brain MRI to quantify ePVS volume and count, longitudinal neuropsychological assessment, and cardiac MRI to quantify aortic stiffness. Linear regressions related (1) PWV to ePVS burden and (2) ePVS burden to cross-sectional and longitudinal neuropsychological performance adjusting for key demographic and medical factors. Higher aortic stiffness related to greater basal ganglia ePVS volume (β = 7.0×10−5, p = 0.04). Higher baseline ePVS volume was associated with worse baseline information processing (β = -974, p = 0.003), executive function (β = -81.9, p < 0.001), and visuospatial performances (β = -192, p = 0.02) and worse longitudinal language (β = -54.9, p = 0.05), information processing (β = -147, p = 0.03), executive function (β = -10.9, p = 0.03), and episodic memory performances (β = -10.6, p = 0.02). Results were similar for ePVS count. Greater arterial stiffness relates to worse basal ganglia ePVS burden, suggesting cardiovascular aging as an etiology. ePVS burden is associated with adverse cognitive trajectory, emphasizing the clinical relevance of ePVS.
The recent Pulwama incident has further strained the already tense relationship between India and Pakistan. India's violation of the UN resolution on Kashmir has exacerbated the situation, leaving ...both countries with seemingly no common ground or shared challenges to bring them to the dialogue table and build confidence and trust for a sustainable relationship. This paper proposes a peace-initiating process prioritising cooperation on common environmental challenges to improve bilateral relations between Pakistan and India. Environmental peacebuilding, which focuses on shared ecological challenges and provides a platform for dialogue and cooperation between rival states, has been explored for a couple of years. However, the cooperative dimensions of environmental peacebuilding have yet to be studied in bilateral relations between Pakistan and India. This paper provides a brief qualitative analysis of relations between two countries, highlights the potential for environmental peacebuilding to improve their relationship, and addresses challenges to successfully implementing this approach.
Bibliography Entry
Khan, Omair Farooq. 2023. "Pakistan-India Bilateral Relations and Application of Environmental Peacebuilding." Margalla Papers 27 (1): 155-165.
Enlarged perivascular spaces (ePVS) may adversely affect cognition. Little is known about how basal ganglia ePVS interact with apolipoprotein (APOE)-ε4 status. Vanderbilt Memory and Aging Project ...participants (n = 326, 73 ± 7, 59% male) underwent 3 T brain MRI at baseline to assess ePVS and longitudinal neuropsychological assessments. The interaction between ePVS volume and APOE-ε4 carrier status was related to baseline outcomes using ordinary least squares regressions and longitudinal cognition using linear mixed-effects regressions. ePVS volume interacted with APOE-ε4 status on cross-sectional naming performance (β = −0.002, p = 0.002), and executive function excluding outliers (β = 0.001, p = 0.009). There were no significant longitudinal interactions (p-values>0.10) except for Coding excluding outliers (β = 0.002, p = 0.05). While cross-sectional models stratified by APOE-ε4 status indicated greater ePVS related to worse cognition mostly in APOE-ε4 carriers, longitudinal models stratified by APOE-ε4 status showed greater ePVS volume related to worse cognition among APOE-ε4 non-carriers only. Results indicated that greater ePVS volume interacts with APOE-ε4 status on cognition cross-sectionally. Longitudinally, the association of greater ePVS volume and worse cognition appears stronger in APOE-ε4 non-carriers, possibly due to the deleterious effects of APOE-ε4 on cognition across the lifespan.
•ePVS volume interacts with APOE-ε4 status on cognition cross-sectionally.•Greater ePVS relates to worse cognition in APOE-ε4 carriers cross-sectionally.•No interaction between ePVS volume and APOE-ε4 status on cognition longitudinally.
To determine whether baseline aortic stiffness, measured by aortic pulse wave velocity (PWV), relates to longitudinal cerebral gray or white matter changes among older adults. Baseline cardiac ...magnetic resonance imaging will be used to assess aortic PWV while brain magnetic resonance imaging will be used to assess gray matter and white matter hyperintensity (WMH) volumes at baseline, 18 months, 3 years, 5 years, and 7 years. Approach and Results: Aortic PWV (m/s) was quantified from cardiac magnetic resonance. Multimodal 3T brain magnetic resonance imaging included
-weighted imaging for quantifying gray matter volumes and
-weighted fluid-attenuated inversion recovery imaging for quantifying WMHs. Mixed-effects regression models related baseline aortic PWV to longitudinal gray matter volumes (total, frontal, parietal, temporal, occipital, hippocampal, and inferior lateral ventricle) and WMH volumes (total, frontal, parietal, temporal, and occipital) adjusting for age, sex, race/ethnicity, education, cognitive diagnosis, Framingham stroke risk profile,
(apolipoprotein E)-ε4 carrier status, and intracranial volume. Two hundred seventy-eight participants (73±7 years, 58% male, 87% self-identified as non-Hispanic White, 159 with normal cognition, and 119 with mild cognitive impairment) from the Vanderbilt Memory & Aging Project (n=335) were followed on average for 4.9±1.6 years with PWV measurements occurring from September 2012 to November 2014 and longitudinal brain magnetic resonance imaging measurements occurring from September 2012 to June 2021. Higher baseline aortic PWV was related to greater decrease in hippocampal (β=-3.6 mm
/y/m/s; 95% CI, -7.2 to -0.02
=0.049) and occipital lobe (β=-34.2 mm
/y/m/s; 95% CI, -67.8 to -0.55
=0.046) gray matter volume over time. Higher baseline aortic PWV was related to greater increase in WMH volume over time in the temporal lobe (β=17.0 mm
/y/m/s; 95% CI, 7.2-26.9
<0.001). All associations may be driven by outliers.
In older adults, higher baseline aortic PWV related to greater decrease in gray matter volume and greater increase in WMHs over time. Because of unmet cerebral metabolic demands and microvascular remodeling, arterial stiffening may preferentially affect certain highly active brain regions like the temporal lobes. These same regions are affected early in the course of Alzheimer disease.
Objective
To compare the risk of resistant hypertension (RHTN) in patients with systemic lupus erythematosus (SLE) and in controls without SLE, and to define factors associated with RHTN in patients ...with SLE.
Methods
We studied 1,044 patients with SLE and 5,241 control subjects using de‐identified electronic health records from a tertiary care center. SLE was defined as ≥4 International Classification of Diseases, Ninth Revision codes for SLE and antinuclear antibody titer ≥1:160. RHTN was defined as uncontrolled blood pressure on 3 antihypertensive medications or requiring 4 or more antihypertensives to attain control. First, we compared the risk of RHTN between groups. Second, we examined the association between RHTN and all‐cause mortality in patients with SLE.
Results
RHTN was nearly twice as prevalent in patients with SLE compared to control subjects (10.2% and 5.3%, respectively), with an incidence rate of 10.2 versus 6.1 cases per 1,000 person‐years of observation (hazard ratio HR 1.72 95% confidence interval 1.28–2.30; P < 0.001, adjusted for age, sex, race, baseline end‐stage renal disease ESRD, creatinine, and calendar year). In patients with SLE, we found associations between RHTN and black race, lower renal function, hypercholesterolemia, and increased inflammatory markers. RHTN was associated with a significantly higher mortality risk (HR 2.91, P = 0.0005) after adjustment for age, sex, race, calendar year, creatinine, baseline ESRD, and number of visits.
Conclusion
Patients with SLE have a higher risk of RHTN compared to frequency‐matched controls, independent of multiple covariates. RHTN is an important comorbidity for clinicians to recognize in SLE, because it is associated with a higher risk of mortality.
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