scholarly journals PLACENTAL STEREOLOGY: SPANNING THE LEVELS FROM MOLECULE TO WHOLE ORGAN

2011 ◽  
Vol 28 (3) ◽  
pp. 121
Author(s):  
Terry M Mayhew

Stereology can provide hard (functionally-relevant) quantitative information at different levels of 3D structural organization. My researches have applied established methods to study organ function and developed novel methods to study subcellular localization of marker probes. We have studied whole-organ function (passive diffusion) in the human placenta and quantified various processes at tissue and subcellular levels and in normal and complicated pregnancies. Fetoplacental angiogenesis and villous growth and maturation involve phased changes particularly around mid-gestation. Growth is associated with increased numbers of cells or nuclei and counts have shown that villous trophoblast continuously renews itself via cytotrophoblast (CT) proliferation and recruitment and syncytiotrophoblast (ST) differentiation and extrusion. Integration of these processes results in changes in total oxygen (O2) diffusive conductance which match the growing fetal mass. Similar processes occur during development of the mouse placenta and at least some are compromised in human pregnancies. For example: [a] in pure pre-eclampsia (PE), villous and fetoplacental vascular volumes and surfaces are similar to those seen in uncomplicated pregnancies but reduced in pure intrauterine growth restriction (IUGR) and in PE+IUGR; [b] trophoblast extrusion is accelerated in PE and IUGR but the latter exhibits reduced CT proliferation and this perturbed steady state leads to smaller trophoblast volumes and surfaces; [c] O2 diffusive conductances alter in various pregnancy complications, including IUGR and PE+IUGR; [d] fetal weight is diminished, but diffusive transport increases, in placentas from mice exposed to urban air pollution. Finally, innovations in quantitative immunoelectron microscopy (immunoEM) have produced a portfolio of methods for revealing non-random distributions of marker gold particles in different cellular compartments and for testing whether patterns shift following experimental manipulation. Recently, the methods have been extended to study tissue and cellular distributions of nanoparticles.

Placenta ◽  
2017 ◽  
Vol 57 ◽  
pp. 280
Author(s):  
Eva Haeussner ◽  
Christoph Schmitz ◽  
David Grynspan ◽  
Franz Edler von Koch ◽  
Hans-Georg Frank

mBio ◽  
2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Allan L. Chen ◽  
Elliot W. Kim ◽  
Justin Y. Toh ◽  
Ajay A. Vashisht ◽  
Andrew Q. Rashoff ◽  
...  

ABSTRACT The inner membrane complex (IMC) of Toxoplasma gondii is a peripheral membrane system that is composed of flattened alveolar sacs that underlie the plasma membrane, coupled to a supporting cytoskeletal network. The IMC plays important roles in parasite replication, motility, and host cell invasion. Despite these central roles in the biology of the parasite, the proteins that constitute the IMC are largely unknown. In this study, we have adapted a technique named proximity-dependent biotin identification (BioID) for use in T. gondii to identify novel components of the IMC. Using IMC proteins in both the alveoli and the cytoskeletal network as bait, we have uncovered a total of 19 new IMC proteins in both of these suborganellar compartments, two of which we functionally evaluate by gene knockout. Importantly, labeling of IMC proteins using this approach has revealed a group of proteins that localize to the sutures of the alveolar sacs that have been seen in their entirety in Toxoplasma species only by freeze fracture electron microscopy. Collectively, our study greatly expands the repertoire of known proteins in the IMC and experimentally validates BioID as a strategy for discovering novel constituents of specific cellular compartments of T. gondii. IMPORTANCE The identification of binding partners is critical for determining protein function within cellular compartments. However, discovery of protein-protein interactions within membrane or cytoskeletal compartments is challenging, particularly for transient or unstable interactions that are often disrupted by experimental manipulation of these compartments. To circumvent these problems, we adapted an in vivo biotinylation technique called BioID for Toxoplasma species to identify binding partners and proximal proteins within native cellular environments. We used BioID to identify 19 novel proteins in the parasite IMC, an organelle consisting of fused membrane sacs and an underlying cytoskeleton, whose protein composition is largely unknown. We also demonstrate the power of BioID for targeted discovery of proteins within specific compartments, such as the IMC cytoskeleton. In addition, we uncovered a new group of proteins localizing to the alveolar sutures of the IMC. BioID promises to reveal new insights on protein constituents and interactions within cellular compartments of Toxoplasma.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gianluca Grimalda ◽  
Nancy R. Buchan ◽  
Orgul D. Ozturk ◽  
Adriana C. Pinate ◽  
Giulia Urso ◽  
...  

AbstractTheory posits that situations of existential threat will enhance prosociality in general and particularly toward others perceived as belonging to the same group as the individual (parochial altruism). Yet, the global character of the COVID-19 pandemic may blur boundaries between ingroups and outgroups and engage altruism at a broader level. In an online experiment, participants from the U.S. and Italy chose whether to allocate a monetary bonus to a charity active in COVID-19 relief efforts at the local, national, or international level. The purpose was to address two important questions about charitable giving in this context: first, what influences the propensity to give, and second, how is charitable giving distributed across different levels of collective welfare? We found that personal exposure to COVID-19 increased donations relative to those not exposed, even as levels of environmental exposure (numbers of cases locally) had no effect. With respect to targets of giving, we found that donors predominantly benefitted the local level; donations toward country and world levels were half as large. Social identity was found to influence charity choice in both countries, although an experimental manipulation of identity salience did not have any direct effect.


2019 ◽  
Vol 40 (6) ◽  
pp. 907-912 ◽  
Author(s):  
Mohamed Nazhat Al Yafi ◽  
Michel Alain Danino ◽  
Ali Izadpanah ◽  
Edouard Coeugniet

Abstract Frostbite causes tissue damage through five major mechanisms, out of which two are amenable to treatment. The first-line treatment is rapid rewarming therapy using water at 40°C to 42°C, which addresses the formation of ice crystals in the intra and extra cellular compartments. The second mechanism is progressive tissue ischemia after rewarming and is only accessible to a second-line therapy represented by thrombolysis. This study aimed to determine the efficacy of thrombolysis. This is a single-center retrospective cohort study, where it was aimed to evaluate two groups of patients. A total of 18 patients were included in this study. Mean times between injury to thrombolytic therapy and admission to thrombolytic therapy was 26.04 hours (SD 13.6) and 9.65 hours (SD 9.89), respectively. All patients suffered injuries ranging from second-degree deep to third degree. The rate of patients having complete, partial, and no angiographic responses were 55.6%, 11.1%, and 33.3%, respectively. The main outcome of interest showed that 11 (61.1%) patients in total had amputations at different levels. Results showed that in the intervention group, five (55.6%) of the patients had amputations compared with six (66.7%) from the control group (P = .6) at comparable levels of amputation. The literature supports that the use of intra-arterial tissue plasminogen activator might be beneficial for severe cases of frostbites; however, it lacks of studies of major significance and results are often controversial. Our study has not shown statistically significant results on amputation levels and cannot support the hypothesis of efficacy of thrombolytic therapy.


2009 ◽  
Vol 107 (4) ◽  
pp. 1258-1265 ◽  
Author(s):  
Dmitriy A. Yablonskiy ◽  
Alexander L. Sukstanskii ◽  
Jason C. Woods ◽  
David S. Gierada ◽  
James D. Quirk ◽  
...  

The structure and integrity of pulmonary acinar airways and their changes in different diseases are of great importance and interest to a broad range of physiologists and clinicians. The introduction of hyperpolarized gases has opened a door to in vivo studies of lungs with MRI. In this study we demonstrate that MRI-based measurements of hyperpolarized 3He diffusivity in human lungs yield quantitative information on the value and spatial distribution of lung parenchyma surface-to-volume ratio, number of alveoli per unit lung volume, mean linear intercept, and acinar airway radii—parameters that have been used by lung physiologists for decades and are accepted as gold standards for quantifying emphysema. We validated our MRI-based method in six human lung specimens with different levels of emphysema against direct unbiased stereological measurements. We demonstrate for the first time MRI images of these lung microgeometric parameters in healthy lungs and lungs with different levels of emphysema (mild, moderate, and severe). Our data suggest that decreases in lung surface area per volume at the initial stages of emphysema are due to dramatic decreases in the depth of the alveolar sleeves covering the alveolar ducts and sacs, implying dramatic decreases in the lung's gas exchange capacity. Our novel methods are sufficiently sensitive to allow early detection and diagnosis of emphysema, providing an opportunity to improve patient treatment outcomes, and have the potential to provide safe and noninvasive in vivo biomarkers for monitoring drug efficacy in clinical trials.


Author(s):  
Aswathi Sudhir ◽  
Ramesh Talreja

The objective of the current work is to conduct a systematic analysis on the effects of manufacturing induced defects such as random distribution of fibers and presence of voids in matrix on the damage initiation in polymeric composites. Upon infusing resin, the initial fiber configuration undergoes perturbation and results in a random distribution with pockets of resin rich areas and fiber clusters. In addition, this could result in micro voids (between the fibers in the bundle) and macro voids (between the fiber bundles). A novel methodology has been put forward to generate random distributions of fibers that would simulate different levels of perturbations in the manufacturing process resulting in different configurations of fiber clusters. An embedded Representative Volume Element (RVE) approach has been adopted in a finite element model to calculate the stress fields without artificial effects of the RVE boundary. Damage initiation is then analyzed using a previously proposed energy based criterion for cavitation in polymers.


Blood ◽  
2011 ◽  
Vol 118 (18) ◽  
pp. 4780-4788 ◽  
Author(s):  
John C. P. Kingdom ◽  
Sascha Drewlo

Abstract Randomized control trials show beneficial effects of heparin in high-risk pregnancies to prevent preeclampsia and intrauterine growth restriction. However, the lack of placental pathology data in these trials challenges the assumption that heparin is a placental anticoagulant. Recent data show that placental infarction is probably associated with abnormalities in development of the placenta, characterized by poor maternal perfusion and an abnormal villous trophoblast compartment in contact with maternal blood, than with maternal thrombophilia. At-risk pregnancies may therefore be predicted by noninvasive prenatal testing of placental function in mid-pregnancy. Heparin has diverse cellular functions that include direct actions on the trophoblast. Dissecting the non–anticoagulant actions of heparin may indicate novel and safer therapeutic targets to prevent the major placental complications of pregnancy.


Author(s):  
C. Brownlee

Marine organisms have long provided ideal systems for the study of development. The reasons for this are essentially twofold. Firstly, gametes, zygotes and embryos of many species are relatively accessible, facilitating observation and experimental manipulation. Secondly, the exceptional diversity to be found in the sea allows wide ranging comparative and evolutionary studies. The aim of this meeting was to highlight significant advances in developmental biology research using marine organisms and to bring together workers from a variety of disciplines to encourage cross-fertilization of ideas and comparisons between different systems. Particular attention was paid to new approaches for solving fundamental problems at different levels of complexity and organization. The meeting was organized such that parallel developmental processes in different systems, both animal and plant, could be compared. Sessions covered egg activation/cell cycle control; polarization/early development; embryogenesis/larval development; and the interaction between development and environment. Examples were chosen from a wide range of organisms, including molluscs, echinoderms, asddians, echiuran and polychaete worms, ctenophores, copepods, amphioxus, fish and algae (Brownlee, 1993).


1992 ◽  
Vol 65 (4) ◽  
pp. 836-850 ◽  
Author(s):  
Walter H. Waddell ◽  
James R. Parker

Abstract In an effort to find out if compound composition could help explain the observed differences in “chip/chunk tearing” on worn off-the-road tires from two manufacturers, direct characterizations were made on tread lugs from the two tires. Two nondestructive direct analytical methods were used. They are photoacoustical Fourier transform infrared spectroscopy (PA-FTIR) and proton induced x-ray emission spectroscopy (PIXE). These techniques were also used to examine a variety of rubber compounding ingredients, such as polymers and fillers, and model tire compounds containing different levels of these ingredients. PA-FTIR requires essentially no sample preparation. It was successfully used to determine the polymer structure and to suggest the nonblack filler type in highly loaded carbon-black filled, sulfur-cured compounds and in tire sections. The characterization was based upon structural information derived from vibrational band frequencies. Elemental information was obtained by using direct PIXE spectral analysis of polymers, fillers, and two worn off-the-road tire tread lugs. Again, no sample preparation was needed and quantitative information was obtained on the elements present. Results show that the tire that did not display a tear problem was manufactured with a cushion (tread base) and a tread (cap), both containing silica at the 12–15 phr levels. The tire that had a visible chip/chunk problem was constructed with two layers of a very similar stock, but neither layer contains silica.


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