scholarly journals Antibody-Mediated Protection againstPlasmodiumSporozoites Begins at the Dermal Inoculation Site

mBio ◽  
2018 ◽  
Vol 9 (6) ◽  
Author(s):  
Yevel Flores-Garcia ◽  
Gibran Nasir ◽  
Christine S. Hopp ◽  
Christian Munoz ◽  
Amanda E. Balaban ◽  
...  
Keyword(s):  
Protective Effect ◽  
Blood Vessels ◽  
Blood Circulation ◽  
Life Cycle Stage ◽  
Malarial Parasite ◽  
Content Type ◽  
Inoculation Site ◽  
Neutralizing Capacity ◽  
Circulating Antibodies ◽  
Parasite Challenge

ABSTRACTPlasmodiumsporozoites are injected into the skin as mosquitoes probe for blood. From here, they migrate through the dermis to find blood vessels which they enter in order to be rapidly carried to the liver, where they invade hepatocytes and develop into the next life cycle stage, the exoerythrocytic stage. Once sporozoites enter the blood circulation, they are found in hepatocytes within minutes. In contrast, sporozoite exit from the inoculation site resembles a slow trickle and occurs over several hours. Thus, sporozoites spend the majority of their extracellular time at the inoculation site, raising the hypothesis that this is when the malarial parasite is most vulnerable to antibody-mediated destruction. Here, we investigate this hypothesis and demonstrate that the neutralizing capacity of circulating antibodies is greater at the inoculation site than in the blood circulation. Furthermore, these antibodies are working, at least in part, by impacting sporozoite motility at the inoculation site. Using actively and passively immunized mice, we found that most parasites are either immobilized at the site of injection or display reduced motility, particularly in their net displacement. We also found that antibodies severely impair the entry of sporozoites into the bloodstream. Overall, our data suggest that antibodies targeting the migratory sporozoite exert a large proportion of their protective effect at the inoculation site.IMPORTANCEStudies in experimental animal models and humans have shown that antibodies againstPlasmodiumsporozoites abolish parasite infectivity and provide sterile immunity. While it is well documented that these antibodies can be induced after immunization with attenuated parasites or subunit vaccines, the mechanisms by and location in which they neutralize parasites have not been fully elucidated. Here, we report studies indicating that these antibodies display a significant portion of their protective effect in the skin after injection of sporozoites and that one mechanism by which they work is by impairing sporozoite motility, thus diminishing their ability to reach blood vessels. These results suggest that immune protection against malaria begins at the earliest stages of parasite infection and emphasize the need of performing parasite challenge in the skin for the evaluation of protective immunity.

Identification of asset life cycle stage: case study in heavy-duty truck fleet

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Oscar Daniel Rivera Baena ◽  
Maria Valentina Clavijo Mesa ◽  
Carmen Elena Patino Rodriguez ◽  
Fernando Jesus Guevara Carazas
Keyword(s):  
Life Cycle ◽  
Design Methodology ◽  
Life Cycle Stage ◽  
Waste Collection ◽  
Content Type ◽  
Heavy Duty Truck ◽  
Maintenance Work ◽  
Operational Decision Making ◽  
The Moment

PurposeThis paper aims to determine the stage of the life cycle where the trucks of a waste collection fleet from a Colombian city are located through a reliability approach. The reliability analysis and the evaluation of curve of operational costs allow to know the moment in which it is necessary to make decisions regarding an asset, its maintenance or possible replacement.Design/methodology/approachFor a dataset presented as maintenance work orders, the time to failures (TTFs) for each vehicle in the fleet were calculated. Then, a probability density function for those TTFs was fitted to locate each vehicle in a region of the bathtub curve and to calculate the reliability of the whole fleet. A general functional analysis was also developed to understand the function of the vehicles.FindingsIt was possible to determine that the largest proportion of the fleet was in the final stage of the life cycle, in this sense, the entire fleet represent critical assets which in most of cases could be worth replacement or overhaul.Originality/valueIn this study, an address is exposed for the identification of critical equipment by reliability and statistical analysis. This analysis is also integrated with the maintenance management process. This is a broadly interested topic since it allows to support the maintenance and operational decision-making process, indicating the focus of resource allocation all over the entire asset life cycle.

scholarly journals Shedding Light on the Role of the Skin in Vaccine-Induced Protection against the Malaria Sporozoite

mBio ◽  
2018 ◽  
Vol 9 (6) ◽  
Author(s):  
Johanna Patricia Daily
Keyword(s):  
Plasmodium Falciparum ◽  
Blood Vessels ◽  
Blood Stream ◽  
Mosquito Vectors ◽  
Protective Mechanisms ◽  
Partial Protection ◽  
Content Type ◽  
Shed Light ◽  
In Infants And Children

ABSTRACT The most advanced vaccine against Plasmodium falciparum malaria, RTS,S/AS01, provides partial protection in infants and children living in areas of malaria endemicity. Further understanding its mechanisms of protection may allow the development of improved second-generation vaccines. The RTS,S/AS01 vaccine targets the sporozoites injected by mosquito vectors into the dermis which then travel into the blood stream to establish infection in the liver. Flores-Garcia et al. (Y. Flores-Garcia, G. Nasir, C. S. Hopp, C. Munoz, et al., mBio 9:e02194-18, 2018, https://doi.org/10.1128/mBio.02194-18) shed light on early protective responses occurring in the dermis in immunized animals. They demonstrated that immunization impairs sporozoite motility and entry into blood vessels. Furthermore, they established that challenge experiments performed using a dermal route conferred greater protection than intravenous challenge in immunized mice. Thus, the dermal challenge approach captures the additional protective mechanisms occurring in the dermis that reflect the natural physiology of infection. Those studies highlighted the fascinating biology of skin-stage sporozoites and provided additional insights into vaccine-induced protection.

Is there a decision to make, boss? From understanding SME growth to managing employees' learning preferences

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Steven Tam ◽  
David E. Gray
Keyword(s):  
Life Cycle ◽  
High Growth ◽  
Life Cycle Stage ◽  
Learning Preferences ◽  
Best Interests ◽  
Structured Interviews ◽  
Managerial Decision ◽  
Content Type ◽  
Learning Practices ◽  
Life Cycle Stages

PurposeThis study examines employees' learning preferences in small and medium-sized enterprises (SMEs) at different life-cycle stages.Design/methodology/approachThe study has two phases. Phase I classified a sample of 30 Hong Kong SMEs into three different life-cycle stages (inception, high growth or maturity). Phase II then explored/compared their employees' learning practices in terms of importance using a mixed-method design through an online learning questionnaire followed by face-to-face semi-structured interviews.FindingsBased on a list of 32 learning practices common to SME workplaces, the study identified how SME employees perceive the importance of a learning practice. The top 5 and the bottom 5 learning practices in SMEs across life-cycle stages are presented to promote best interests for SME executives.Research limitations/implicationsWhile SME learning is highly varied, this study sheds light on some traceable context about it as an SME grows. Similar studies with additional SMEs, including SMEs in other locations, are encouraged to strengthen the findings.Practical implicationsThe findings help SME executives understand what learning practices are most important (or least important) for their employees, given the life-cycle stage of the firm. Aligning a business with employees' learning preferences in a timely fashion is a managerial decision to be made for driving organizational effectiveness.Originality/valueIt is among the first studies connecting employee learning in SMEs and organizational life cycle to address a critical but missing inquiry.

Cognitive Imaging

2018 ◽  
Vol 12 (2) ◽  
pp. 1-16 ◽  
Author(s):  
Vitaliy L. Rayz ◽  
David Saloner ◽  
Julia M. Rayz ◽  
Victor Raskin
Keyword(s):  
Blood Vessels ◽  
Blood Circulation ◽  
Image Artifacts ◽  
Cognitive Computing ◽  
Extended Version ◽  
Imaging Analysis ◽  
Post Processing ◽  
Computing Technology ◽  
Circulation Modeling ◽  
A Minor

This article, an extended version of ICCI*CC-2017 paper, co-authored by biomedical engineers specializing in brain blood circulation modeling and by experts in meaning-based NLP. This article suggests a cognitive computing technology for medical imaging analysis that removes image artifacts resulting in visual deviations from reality, such as discontinuous blood vessels or two vessels shown merged when they are not. It is implemented by supplying the pertinent knowledge that humans have to the computer and letting it initiate the corrective post-processing. The existing OST resource is centered on the ontology that is made to accommodate the domain with a minor adjustment effort; however, any ontology can be used, as demonstrated in this article. The examples from the ontology demonstrate the disparities between what the image shows and what the human knows. The computer detects them autonomously and can initiate the appropriate post-processing. If and when this cognitive imaging prevails, the post-processed images may replace the current ones as legitimate artifact-free MRIs.

The fine anatomy of the human spinal meninges

1988 ◽  
Vol 69 (2) ◽  
pp. 276-282 ◽  
Author(s):  
David S. Nicholas ◽  
Roy O. Weller
Keyword(s):  
Spinal Cord ◽  
Blood Vessels ◽  
Transverse Section ◽  
Human Cerebral Cortex ◽  
Pia Mater ◽  
Content Type ◽  
Inner Aspect ◽  
Dentate Ligament ◽  
Arachnoid Mater ◽  
Fine Print

✓ The fine anatomy of the human spinal meninges was examined in five postmortem spinal cords taken within 12 hours after death from patients aged 15 months to 46 years. Specimens of spinal cord were viewed in transverse section and from the dorsal and ventral aspects by scanning electron microscopy. Transverse sections of spinal cord and meninges were also examined by light microscopy. The arachnoid mater was seen to be closely applied to the inner aspect of the dura. An intermediate fenestrated leptomeningeal layer was observed attached to the inner aspect of the arachnoid mater and was reflected ventrally to form a series of dorsal septa. As it arborized laterally over the surface of the cord to surround nerves and blood vessels, the intermediate layer became highly fenestrated but remained distinct from the pia and arachnoid mater. The pia mater appeared to form a continuous layer which was reflected off the surface of the cord to coat blood vessels within the subarachnoid space in a manner similar to that described in the leptomeninges over the human cerebral cortex. Each dentate ligament consisted of a collagenous core which was continuous with the subpial connective tissue and was attached at intervals to the dura; pia-arachnoid cells coated the surface of the dentate ligaments. The present study suggests that the fine anatomy of the human spinal meninges differs significantly from that described in other mammals.

scholarly journals Interleukin-10 (IL-10) Produced by Mutant Toxic Shock Syndrome Toxin 1 Vaccine-Induced Memory T Cells Downregulates IL-17 Production and Abrogates the Protective Effect against Staphylococcus aureus Infection

2019 ◽  
Vol 87 (10) ◽  
Author(s):  
Kouji Narita ◽  
Dong-Liang Hu ◽  
Krisana Asano ◽  
Akio Nakane
Keyword(s):  
Staphylococcus Aureus ◽  
T Cells ◽  
Infectious Diseases ◽  
Protective Effect ◽  
Toxic Shock Syndrome ◽  
Long Term Memory ◽  
Toxic Shock ◽  
Content Type ◽  
Memory Phase ◽  
Toxic Shock Syndrome Toxin

ABSTRACT Development of long-term memory is crucial for vaccine-induced adaptive immunity against infectious diseases such as Staphylococcus aureus infection. Toxic shock syndrome toxin 1 (TSST-1), one of the superantigens produced by S. aureus, is a possible vaccine candidate against infectious diseases caused by this pathogen. We previously reported that vaccination with less toxic mutant TSST-1 (mTSST-1) induced T helper 17 (Th17) cells and elicited interleukin-17A (IL-17A)-mediated protection against S. aureus infection 1 week after vaccination. In the present study, we investigated the host immune response induced by mTSST-1 vaccination in the memory phase, 12 weeks after the final vaccination. The protective effect and IL-17A production after vaccination with mTSST-1 were eliminated because of IL-10 production. In the presence of IL-10-neutralizing monoclonal antibody (mAb), IL-17A production was restored in culture supernatants of CD4+ T cells and macrophages sorted from the spleens of vaccinated mice. Vaccinated mice treated with anti-IL-10 mAb were protected against systemic S. aureus infection in the memory phase. From these results, it was suggested that IL-10 produced in the memory phase suppresses the IL-17A-dependent vaccine effect through downregulation of IL-17A production.

Cerebral circulation time with ruptured intracranial aneurysms

1974 ◽  
Vol 41 (4) ◽  
pp. 415-420 ◽  
Author(s):  
Shige-Hisa Okawara ◽  
Jun Kimura ◽  
Joo Y. Hahn
Keyword(s):  
Intracranial Aneurysms ◽  
Blood Circulation ◽  
Circulation Time ◽  
Arterial Phase ◽  
Preoperative Treatment ◽  
Content Type ◽  
Arterial Perfusion ◽  
Ruptured Intracranial Aneurysm ◽  
Ruptured Intracranial Aneurysms ◽  
Cerebral Blood Circulation

✓ The cerebral blood circulation time (CT), including the length of the arterial phase, was obtained from rapid serial angiograms in 114 patients with ruptured intracranial aneurysms. The average CT of 7.2 sec, with a mean arterial phase of 3.1 sec, was much longer than the normal average CT of 5.4 sec with its 2.4 sec arterial phase. Longer circulation times were observed with the higher Botterell grades of clinical condition, high arterial perfusion and CSF pressures, and in cases with angiographic evidence of arterial spasm, hematoma, or hydrocephalus. Values of CT greater than 8.0 sec were associated with increased mortality and morbidity and vice versa. The value of the cerebral blood circulation time as a guide to preoperative treatment and to the prognosis of cases of ruptured intracranial aneurysm is suggested.

A role of the central catecholamine neuron in cerebral circulation

1986 ◽  
Vol 65 (3) ◽  
pp. 370-375 ◽  
Author(s):  
Hideyoshi Yokote ◽  
Toru Itakura ◽  
Kunio Nakai ◽  
Ichiro Kamei ◽  
Harumichi Imai ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Blood Vessels ◽  
Cerebral Circulation ◽  
Intracerebral Injection ◽  
Neuron System ◽  
Content Type ◽  
6 Hydroxydopamine ◽  
Catecholamine Neuron

✓ The effect of the central catecholaminergic neurons on the cerebral microcirculation was investigated by means of a unilateral intracerebral injection of 6-hydroxydopamine (6-OHDA) which produced the degeneration of catecholamine (CA) nerve terminals. Subsequent observation with CA histofluorescence revealed an absence of CA fibers in the vicinity of the 6-OHDA injection site. A significant increase in regional cerebral blood flow (rCBF), measured by the hydrogen clearance method, was demonstrated in the CA-depleted cortex under normocapnia as compared with rCBF in the control cortex (CA-depleted cortex 47.0 ± 2.8 ml/100 gm/min; control cortex 38.5 ± 3.5 ml/100 gm/min; p < 0.005). The increased rCBF in the cortex treated with 6-OHDA was suppressed by the iontophoretic replacement of noradrenaline (NA) to the CA-depleted cortex. An iontophoretic replacement of 10−5 M dopamine (DA) mildly suppressed the increased rCBF in the 6-OHDA-treated cortex. The CO2 reactivity in the CA-depleted cortex was significantly lower than that of the control cortex (CA-depleted cortex 2.13% ± 0.67%/mm Hg; control cortex 3.53% ± 0.70%/mm Hg). No change was noticeable in the cerebral glucose metabolism in the CA-depleted cortex in an investigation based on tritiated (3H)-deoxyglucose uptake. It is suggested that the 6-OHDA-induced change in cerebral blood flow (CBF) is not secondary to alterations in cerebral metabolic rate, and that the central NA neuron system innervating intraparenchymal blood vessels regulates CBF through a direct vasoconstrictive effect on the cerebral blood vessels. The central DA neuron system may modulate the cerebral circulation as a mild vasoconstrictor.

Experimental chronic subdural hematoma in mice

1987 ◽  
Vol 67 (5) ◽  
pp. 710-716 ◽  
Author(s):  
Hisashi Aikawa ◽  
Kinuko Suzuki
Keyword(s):  
Body Weight ◽  
Blood Vessels ◽  
Subdural Hematoma ◽  
Intraperitoneal Injection ◽  
Intraventricular Hemorrhage ◽  
Chronic Subdural Hematoma ◽  
Content Type ◽  
Single Intraperitoneal Injection ◽  
Thin Walled ◽  
Fine Print

✓ A new experimental model of chronic subdural hematoma in mice is described. A single intraperitoneal injection of 6-aminonicotinamide (25 mg/kg body weight) on the 5th postnatal day induced hydrocephalus in mice with almost 100% success. Approximately 60% of the mice spontaneously developed intracranial hemorrhage 20 days after the injection. About 1 week after the hemorrhage, a lens-shaped or spherical subdural hematoma was observed, accompanied by marked dilatation of the lateral ventricles and intraventricular hemorrhage. Histological examination revealed that the hematoma contained well-organized outer and inner membranes. Fresh hemorrhage surrounded by many hemosiderin-laden macrophages was seen at the margin of the hematoma adjacent to the organizing outer membrane, in which many fibroblasts and blood vessels were noted. The inner membrane of the hematoma was made up of several tiers of flattened cells with thin-walled blood vessels. The gross morphology and histology of these hematomas closely resembled those of human chronic subdural hematoma.

Sudden loss of vision following alcohol block of the infraorbital nerve

1973 ◽  
Vol 38 (5) ◽  
pp. 655-657 ◽  
Author(s):  
James W. Markham
Keyword(s):  
Blood Vessels ◽  
Infraorbital Nerve ◽  
Unusual Complication ◽  
Predisposing Factor ◽  
Content Type ◽  
Sudden Loss ◽  
Loss Of Vision ◽  
Tic Douloureux ◽  
Retinal Artery ◽  
Fine Print

✓ The unusual complication of sudden ipsilateral loss of vision following alcohol block of the infraorbital nerve for tic douloureux is described and the possible physiopathology discussed. The author believes that spasm of the central retinal artery was the cause and that repeated injections may have been a predisposing factor. Review of other cases reported shows that the loss of vision has been attributed to embolization of injected agents via collateral blood vessels.

Sign in / Sign up

Export Citation Format

Share Document