Alpha globin is expressed in the endothelial cells of human resistance arteries where it binds to endothelial nitric oxide synthase and limits release of the vasodilator nitric oxide. Genomic ...deletion of the alpha globin gene (HBA) is common among Black Americans and could lead to increased endothelial nitric oxide signaling and reduced risk of hypertension.
Community-dwelling US adults aged 45 years or older were enrolled and examined from 2003 to 2007, followed by telephone every 6 months, and reexamined from 2013 to 2016. At both visits, trained personnel performed standardized, in-home blood pressure measurements and pill bottle review. Prevalent hypertension was defined as systolic blood pressure ≥ 140mmHg or diastolic blood pressure ≥ 90mmHg or anti-hypertensive medication use. Droplet digital PCR was used to determine HBA copy number. The associations of HBA copy number with prevalent hypertension, resistant hypertension, and incident hypertension were estimated using multivariable regression.
Among 9,684 Black participants, 7,439 (77%) had hypertension at baseline and 1,044 of those had treatment-resistant hypertension. 1,000 participants were not hypertensive at baseline and participated in a follow up visit; 517 (52%) developed hypertension over median 9.2 years follow-up. Increased HBA copy number was not associated with prevalent hypertension (PR = 1.00; 95%CI 0.98,1.02), resistant hypertension (PR = 0.95; 95%CI 0.86,1.05), or incident hypertension (RR = 0.96; 95%CI 0.86,1.07).
There were no associations between increased HBA copy number and risk of hypertension. These findings suggest that variation in alpha globin gene copy number does not modify the risk of hypertension among Black American adults.
Recently, we have shown that blocking of junctional adhesion molecule-1/A (JAM-1/A) inhibits basic fibroblast growth factor (bFGF)-induced angiogenesis. Because the process of endothelial cell ...proliferation is a key initial step of neovascularization, we studied the effect of functional knockdown of JAM-1 on human umbilical vein endothelial cell (HUVEC) adhesion and migration induced by bFGF.
We introduced small interfering RNAs specific to JAM-1 in HUVECs, stimulated them with bFGF, and studied the resultant adhesion and migration of these cells on vitronectin and fibronectin. We show that depletion of JAM-1 inhibits bFGF-induced HUVEC migration specifically on vitronectin. This inhibition is not attributable to the failure of junctional organization, because expression and distribution of other junctional proteins remained unaffected. This inhibition was in fact attributed to an inability of JAM-1-depleted HUVECs to adhere and spread on vitronectin. Furthermore, we find that JAM-1-depleted HUVECs failed to activate extracellular signal-related kinase (ERK) in response to bFGF treatment.
Our results show that JAM-1 is required for the bFGF-induced ERK activation that leads to endothelial cell migration on vitronectin. These data thus implicate JAM-1 as an integral part of both bFGF and ERK signaling pathways in endothelial cells.
Megakaryocytes are large, polyploid cells that produce platelets. We have previously reported that calcium- and integrin-binding protein 1 (CIB1) regulates endomitosis in Dami cells. To further ...characterize the role of CIB1 in megakaryopoiesis, we used a Cib1−/− mouse model. Cib1−/− mice have more platelets and BM megakaryocytes than wild-type (WT) controls (P < .05). Furthermore, subsequent analysis of megakaryocyte-CFU production revealed an increase with Cib1 deletion compared with WT (P < .05). In addition, BM from Cib1−/− mice, cultured with thrombopoietin (TPO) for 24 hours, produced more highly polyploid megakaryocytes than WT BM (P < .05). Subsequent analysis of TPO signaling revealed enhanced Akt and ERK1/2 phosphorylation, whereas FAKY925 phosphorylation was reduced in Cib1−/− megakaryocytes treated with TPO. Conversely, platelet recovery in Cib1−/− mice after platelet depletion was attenuated compared with WT (P < .05). This could be the result of impaired adhesion and migration, as adhesion to fibrinogen and fibronectin and migration toward an SDF-1α gradient were reduced in Cib1−/− megakaryocytes compared with WT (P < .05). In addition, Cib1−/− megakaryocytes formed fewer proplatelets compared with WT (P < .05), when plated on fibrinogen. These data suggest that CIB1 plays a dual role in megakaryopoiesis, initially by negatively regulating TPO signaling and later by augmenting proplatelet production.
Transmigration of neutrophils (PMNs) from the vasculature into inflamed tissues, mediated by interactions between PMNs and adhesion molecules on endothelial cells, is an essential aspect of ...inflammation. The crucial adhesion molecules include junctional adhesion molecule (JAM)-A. Investigation of the role of this molecule in models of inflammatory disease has been limited, however, and results in different disease models have varied. No previous study has addressed JAM-A in lung disease or effects on oxidant stress and proinflammatory cytokines. We use JAM-A knockout mice and blocking antibodies to investigate the role of JAM-A in a murine model of acute lung injury (ALI). With either experimental system, we find that absence of JAM-A activity significantly reduces migration of PMNs into the alveolar space, with a resulting decrease in oxidative stress. However, there is no reduction in whole lung activity of PMN-associated myeloperoxidase, presumably reflecting the histologically observed retention of PMNs in lung tissue. Activity of these retained PMNs may account for our failure to find significant change in markers of lung oxidative stress or cytokine and chemokine levels in plasma, lung, and bronchoalveolar lavage fluid. We likewise see no JAM-A-related changes in markers of capillary permeability or lung injury. A similar lack of congruence between effects on PMN migration and tissue injury has been reported in other disease models and for other adhesion molecules in models of ALI. Our results thus confirm the crucial role of JAM-A in PMN transmigration but demonstrate that transmigration is not essential for other aspects of inflammation or for lung injury in ALI.
An important limitation of recombinant adeno-associated virus (rAAV) vector efficiency is the requirement of hostcell-mediated synthesis of double-stranded DNA from the single-stranded genome. We ...have bypassed this step in a specialized self-complementary rAAV (scAAV) vector, by utilizing the tendency of AAV to package DNA dimers when the replicating genome is half the length of the wild type (wt). To produce these vectors efficiently, we have deleted the terminal resolution site (trs) from one rAAV TR, preventing the initiation of replication at the mutated end. These constructs generate single-stranded, inverted repeat genomes, with a wt TR at each end, and a mutated TR in the middle. After uncoating, the viral DNA folds through intramolecular base pairing within the mutant TR, which then proceeds through the genome to form a double-stranded molecule. We have used the scAAV to investigate barriers to rAAV transduction in the mouse liver, muscle and brain. In each tissue, scAAV was characterized by faster onset of gene expression and higher transduction efficiency. This study confirms earlier predictions that complementary-strand DNA synthesis is the primary barrier to rAAV-2 transduction. The scAAV is unaffected by this barrier, and provides an extremely efficient vector for gene transfer into many types of cells in vivo.
Separation of palladium from high level liquid waste (HLLW) solution originated from the reprocessing of spent fuel by PUREX process is carried out by solvent extraction and precipitation methods ...using oximes. In solvent extraction, palladium is extracted from the waste using 1.1×10
−2M α-benzoin oxime in Solvesso 100 as extractant. The loaded organic phase is scrubbed with water prior to the stripping of palladium using the strippants 0.05 M thiourea in 0.1 M HNO
3 and 4 M NH
4OH separately. The recovery of the method is found to be >99.5%. The method has been used to recover Pd in sub mg quantities from actual waste solution originated from the reprocessing of spent fuel from pressurised heavy water reactor (PHWR-HLLW). Studies are also carried out for the separation of palladium using an aqueous solution of sodium salt of dimethyl glyoxime (0.1% w/v) as precipitant. Various parameters which influence the precipitation of palladium such as concentration of the precipitant, concentration of nitric acid in the feed and the behaviour of uranium, plutonium and other fission products at the concentration level encountered in the waste are studied in detail. Under the optimized precipitation conditions separation of Pd is carried out from a synthetic PHWR-HLLW and the recovery is found to be >99.9%. The palladium product obtained from both the methods show high decontamination factors with respect to other fission products and constituents of the waste. Based on these results a scheme has been proposed for the recovery of palladium from HLLW.
A Deep Learning Approach for Malnutrition Detection Ankalaki, Shilpa; G Biradar, Vidyadevi; Naik P, Kishore Kumar ...
International Journal of Online and Biomedical Engineering,
04/2024, Letnik:
20, Številka:
6
Journal Article
Recenzirano
Odprti dostop
The timely detection of malnutrition in children is of paramount importance, as it allows for early intervention and treatment. This proactive approach not only prevents further health deterioration ...but also fosters proper growth, minimizing the long-term consequences of malnutrition, such as stunted growth, impaired cognitive development, and increased vulnerability to diseases. Our work encompasses the creation of a new dataset comprising images of children in Healthy, Undernourished, Stunting, and Wasting categories. The core objective is to assess the deep learning model performance in classifying these children images. The experimentation is carried out by varying epochs, batch size, optimizers AdamW, Adamax, and RMSprop; and different values of the learning rate 0.1, 0.01, 0.001, and 0.0001 during model training. The model is trained on image dataset constructed by cleaning images generated by the stable diffusion model. The model is tested on randomly selected child images from websites. The model successfully classified two classes with 95% accuracy, 97.6% F1 score, precision 97.6%, and 97.6% recall with Adam optimizers, 0.0001 learning rate, and Batch size 4. Additionally, for the four-class categorization scenario, the study broadens the classification. The model achieved 88.87% accuracy, 90.3% recall, 90.2% precision, and an F1 score of 90% for four-class categorization with AdamW optimization, 0.0001 learning rate, and batch size 6. These results are satisfactory for prediction of malnutrition category in children.
Cross talk between glia and neurons is crucial for a variety of biological functions, ranging from nervous system development, axonal conduction, synaptic transmission, neural circuit maturation, to ...homeostasis maintenance. Extracellular vesicles (EVs), which were initially described as cellular debris and were devoid of biological function, are now recognized as key components in cell-cell communication and play a critical role in glia-neuron communication. EVs transport the proteins, lipids, and nucleic acid cargo in intercellular communication, which alters target cells structurally and functionally. A better understanding of the roles of EVs in glia-neuron communication, both in physiological and pathological conditions, can aid in the discovery of novel therapeutic targets and the development of new biomarkers. This review aims to demonstrate that different types of glia and neuronal cells secrete various types of EVs, resulting in specific functions in intercellular communications.
ABSTRACT
In an earlier work, we demonstrated the effectiveness of Bayesian neural networks in estimating the missing line-of-sight velocities of Gaia stars, and published an accompanying catalogue of ...blind predictions for the line-of-sight velocities of stars in Gaia DR3. These were not merely point predictions, but probability distributions reflecting our state of knowledge about each star. Here, we verify that these predictions were highly accurate: the DR3 measurements were statistically consistent with our prediction distributions, with an approximate error rate of 1.5 per cent. We use this same technique to produce a publicly available catalogue of predictive probability distributions for the 185 million stars up to a G-band magnitude of 17.5 still missing line-of-sight velocities in Gaia DR3. Validation tests demonstrate that the predictions are reliable for stars within approximately 7 kpc from the Sun and with distance precisions better than around 20 per cent. For such stars, the typical prediction uncertainty is 25–30 km s−1. We invite the community to use these radial velocities in analyses of stellar kinematics and dynamics, and give an example of such an application.
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