Reviving through human hippocampal newborn neurons.

Recent contradictory data has renewed discussion regarding the existence of adult hippocampal neurogenesis (AHN) in humans, i.e., the continued production of new neurons in the brain after birth. The present review revisits the debate of AHN in humans from a historical point of view in the face of contradictory evidence, analyzing the methods employed to investigate this phenomenon. Thus, to date, of the 57 studies performed in humans that we reviewed, 84% (48) concluded in favor of the presence of newborn neurons in the human adult hippocampus. Besides quality of the tissue (such as postmortem intervals below 26hours as well as tissue conservation and fixation), considerations for assessing and quantify AHN in the human brain require the use of stereology and toxicological analyses of clinical data of the patient.

Texture analysis of cardiovascular magnetic resonance cine images differentiates aetiologies of left ventricular hypertrophy.

AIM: To investigate whether unenhanced cardiovascular magnetic resonance (CMR) balanced steady state free precession (bSSFP) cine images could be analysed using textural analysis (TA) software to differentiate different aetiologies of disease causing increased myocardial wall thickness (left ventricular hypertrophy [LVH]) and indicate the severity of myocardial tissue abnormality. MATERIALS AND METHODS: A mid short axis unenhanced cine frame of 216 patients comprising 50 cases of hypertrophic cardiomyopathy (HCM; predominantly Left ventricular outflow tract obstruction [LVOTO] subtype), 52 cases of cardiac amyloid (CA; predominantly AL: light chain subtype), 68 cases of aortic stenosis (AS), 15 hypertensive patients with LVH (HTN+LVH), and 31 healthy volunteers (HV) underwent TA of the CMR cine images (CMRTA) using TexRAD (TexRAD Ltd, Cambridge, UK). Among the HV, 16/31 were scanned twice to form a test-retest reproducibility cohort. CMRTA comprised a filtration-histogram technique to extract and quantify features using six parameters. RESULTS: Test-retest analysis in the HV showed a medium filter (3 mm) was the most reproducible (intra-class correlation of 0.9 for kurtosis and skewness and 0.8 for mean and SD). Disease cohorts were statistically different (p<0.001) to HV for all parameters. Pairwise comparisons of CMRTA parameters showed kurtosis and skewness was consistently significant in ranking the degree of difference from HV (greatest to least): CA, HCM, LVH+HTN, AS (p<0.001). Similarly, mean, standard deviation, entropy, and mean positive pixel (MPP) were consistent in ranking degree of difference from HV: HCM, CA, AS and HTN+LVH. CONCLUSION: Radiomic features of bSSFP CMR data sets derived using TA show promise in discriminating between the aetiologies of LVH.

Squeezed quadrature fluctuations in a gravitational wave detector using squeezed light.

Squeezed states of light are an important tool for optical measurements below the shot noise limit and for optical realizations of quantum information systems. Recently, squeezed vacuum states were deployed to enhance the shot noise limited performance of gravitational wave detectors. In most practical implementations of squeezing enhancement, relative fluctuations between the squeezed quadrature angle and the measured quadrature (sometimes called squeezing angle jitter or phase noise) are one limit to the noise reduction that can be achieved. We present calculations of several effects that lead to quadrature fluctuations, and use these estimates to account for the observed quadrature fluctuations in a LIGO gravitational wave detector. We discuss the implications of this work for quantum enhanced advanced detectors and even more sensitive third generation detectors.

Quantifying the reduction of airborne infectious viral load using a ventilated patient hood.

BACKGROUND: Healthcare workers treating SARS-CoV-2 patients are at risk of infection by respiratory exposure to patient-emitted, virus-laden aerosols. Source control devices such as ventilated patient isolation hoods have been shown to limit the dissemination of non-infectious airborne particles in laboratory tests, but data on their performance in mitigating the airborne transmission risk of infectious viruses are lacking. AIM: We used an infectious airborne virus to quantify the ability of a ventilated hood to reduce infectious virus exposure in indoor environments. METHODS: We nebulized 109 plaque forming units (pfu) of bacteriophage PhiX174 virus into a ∼30-m3 room when the hood was active or inactive. The airborne concentration of infectious virus was measured by BioSpot-VIVAS and settle plates using plaque assay quantification on the bacterial host Escherichia coli C. The airborne particle number concentration (PNC) was also monitored continuously using an optical particle sizer. FINDINGS: The median airborne viral concentration in the room reached 1.41 × 105 pfu/m3 with the hood inactive. When active, the hood reduced infectious virus concentration in air samples by 374-fold. The deposition of infectious virus on the surface of settle plates was reduced by 87-fold. This was associated with a 109-fold reduction in total airborne particle number escape rate. CONCLUSION: A personal ventilation hood significantly reduced airborne particle escape, considerably lowering infectious virus contamination in an indoor environment. Our findings support the further development of source control devices to mitigate nosocomial infection risk among healthcare workers exposed to airborne viruses in clinical settings.

Effectiveness of portable air filtration on reducing indoor aerosol transmission: preclinical observational trials.

BACKGROUND: While the range of possible transmission pathways of severe acute respiratory syndrome coronavirus-2 in various settings has been investigated thoroughly, most authorities have recently acknowledged the role of aerosol spread in its transmission, especially in indoor environments where ventilation is poor. Engineering controls are needed to mitigate aerosol transmission in high-risk settings including hospital wards, classrooms and offices. AIM: To assess the effectiveness of aerosol filtration by portable air cleaning devices with high-efficiency particulate air filters used in addition to a standard building heating ventilation and air conditioning (HVAC) system. METHODS: Test rooms, including a single-bed hospital room, were filled with test aerosol to simulate aerosol movement. Aerosol counts were measured over time with various portable air cleaning devices and room ventilation systems to quantify the overall aerosol clearance rate. FINDINGS: Portable air cleaning devices were very effective for removal of aerosols. The aerosols were cleared five times faster in a small control room with portable air cleaning devices than in the room with HVAC alone. The single-bed hospital room had an excellent ventilation rate (∼14 air changes per hour) and cleared the aerosols in 20 min. However, with the addition of two air cleaning devices, the clearance time was three times faster. CONCLUSIONS: Inexpensive portable air cleaning devices should be considered for small and enclosed spaces in healthcare settings, such as inpatient rooms and personal protective equipment donning/doffing stations. Portable air cleaning devices are particularly important where there is limited ability to reduce aerosol transmission with building HVAC ventilation.

The homogenous alternative to biomineralization: Zn- and Mn-rich materials enable sharp organismal "tools" that reduce force requirements.

We measured hardness, modulus of elasticity, and, for the first time, loss tangent, energy of fracture, abrasion resistance, and impact resistance of zinc- and manganese-enriched materials from fangs, stings and other "tools" of an ant, spider, scorpion and nereid worm. The mechanical properties of the Zn- and Mn-materials tended to cluster together between plain and biomineralized "tool" materials, with the hardness reaching, and most abrasion resistance values exceeding, those of calcified salmon teeth and crab claws. Atom probe tomography indicated that Zn was distributed homogeneously on a nanometer scale and likely bound as individual atoms to more than » of the protein residues in ant mandibular teeth. This homogeneity appears to enable sharper, more precisely sculpted "tools" than materials with biomineral inclusions do, and also eliminates interfaces with the inclusions that could be susceptible to fracture. Based on contact mechanics and simplified models, we hypothesize that, relative to plain materials, the higher elastic modulus, hardness and abrasion resistance minimize temporary or permanent tool blunting, resulting in a roughly 2/3 reduction in the force, energy, and muscle mass required to initiate puncture of stiff materials, and even greater force reductions when the cumulative effects of abrasion are considered. We suggest that the sharpness-related force reductions lead to significant energy savings, and can also enable organisms, especially smaller ones, to puncture, cut, and grasp objects that would not be accessible with plain or biomineralized "tools".

Approaching the motional ground state of a 10-kg object.

The motion of a mechanical object, even a human-sized object, should be governed by the rules of quantum mechanics. Coaxing them into a quantum state is, however, difficult because the thermal environment masks any quantum signature of the object's motion. The thermal environment also masks the effects of proposed modifications of quantum mechanics at large mass scales. We prepared the center-of-mass motion of a 10-kilogram mechanical oscillator in a state with an average phonon occupation of 10.8. The reduction in temperature, from room temperature to 77 nanokelvin, is commensurate with an 11 orders-of-magnitude suppression of quantum back-action by feedback and a 13 orders-of-magnitude increase in the mass of an object prepared close to its motional ground state. Our approach will enable the possibility of probing gravity on massive quantum systems.

Image reconstruction: Part 1 - understanding filtered back projection, noise and image acquisition.

Image reconstruction is an increasingly complex field in CT. Iterative Reconstruction (IR) is at present an adjunct to standard Filtered Back Projection (FBP) reconstruction, but could become a replacement for it. Due to its potential for scanning at lower radiation doses, IR has received a lot of attention in the medical literature and all vendors offer commercial solutions. Its use in cardiovascular CT has been driven in part due to concerns about radiation dose and image quality. This paper is the first manuscript of a pair. It aims to review the basic principles of CT scanning, to describe image reconstruction using Filtered Back Projection, and to identify the physical processes that contribute to image noise which IR may be able to compensate for. The aim is to enable cardiovascular imagers to understand what happens to the raw data prior to the reconstruction process so they may have a better appreciation of the strengths and weaknesses of the various reconstruction techniques available. The second manuscript of this pair will discuss the various vendor permutations of IR in more detail, including the most recent machine learning based offerings, and critically appraise the current clinical research available on the various IR techniques used in cardiovascular CT.

Over-expression of STP13, a hexose transporter, improves plant growth and nitrogen use in Arabidopsis thaliana seedlings.

In Arabidopsis thaliana, the regulation of hexose levels by the large monosaccharide transporter (MST) gene family influences many aspects of plant growth. The cloning and transgenic expression of one family member (STP13) enabled the manipulation of carbon (C) and nitrogen (N) metabolism in Arabidopsis. Transgenic seedlings constitutively over-expressing STP13 (STP13OX) had increased rates of glucose uptake, higher endogenous sucrose levels and accumulated more total C and biomass per plant when grown on soil-less media supplemented with 55 mM glucose and sufficient N (9 mM nitrate). Furthermore, STP13OX seedlings acquired 90% more total N than the Col-0 seedlings, and had higher levels of expression of the nitrate transporter NRT2.2. In addition, STP13OX seedlings were larger and had higher biomass than Col-0 seedlings when grown under a limiting N condition (3 mM nitrate). Transgene analysis of STP13 reveals that its gene product is localized to the plasma membrane (PM) in tobacco BY-2 suspension cells, that it encodes a functional MST in planta, and that the STP13 promoter directs GUS expression to the vasculature and to leaf mesophyll cells. This work highlights the link between C and N metabolism, demonstrating that a plant's N use may be improved by increasing the availability of C.

Image reconstruction in cardiovascular CT: Part 2 - Iterative reconstruction; potential and pitfalls.

The use of IR in CT previously has been prohibitively complicated and time consuming, however improvements in computer processing power now make it possible on almost all CT scanners. Due to its potential to allow scanning at lower doses, IR has received a lot of attention in the medical literature and has become a successful commercial product. Its use in cardiovascular CT has been driven in part due to concerns about radiation dose and image quality. This manuscript discusses the various vendor permutations of iterative reconstruction (IR) in detail and critically appraises the current clinical research available on the various IR techniques used in cardiovascular CT.

On the use of retrograde tracers for identification of axon collaterals with multiple fluorescent retrograde tracers.

A common method for identifying collateral projections is to inject different retrograde tracers into two targets and examine labeled cells for the presence of both tracers. Double-labeled cells are considered to have collateral projections to the two injection sites. This method is widely considered to underestimate the extent of collaterals. To test the efficiency of double-labeling, we mixed equal volumes of two tracers, injected them into one site in a guinea-pig brain, and counted the resulting labeled cells. Ideally, the tracers would have precisely overlapping injection sites and all labeled cells would contain both tracers. We tested several combinations of tracers: 1) Fast Blue and fluorescein dextran; 2) fluorescein dextran and FluoroGold; 3) fluorescein dextran and FluoroRuby; 4) FluoroGold and green beads; 5) FluoroGold and red beads; 6) FluoroRuby and green beads; and, 7) green beads and red beads. For each combination, a mixture was injected into the left inferior colliculus. After 1 week to allow for transport, labeled cells were counted in the right inferior colliculus and the left temporal cortex. For each mixture, the results were similar for the two areas. The percentage of cells that were double-labeled varied from 0% to 100%, depending on tracer combination. The highest efficiencies (>96%) were observed with red beads and green beads or with FluoroRuby and fluorescein dextran. The limited efficiency of other mixtures could be accounted for only in part by incomplete overlap of the two tracers at the injection site. The results indicate that the specific combination of tracers used to search for collateral projections can greatly affect the findings.

A Simple and Sensitive Method for Quantitative Measurement of Methylmalonic Acid by Turbulent Flow Chromatography and Tandem Mass Spectrometry.

A simple and sensitive method for the detection of methylmalonic acid in serum without derivatization has been developed. This method implements protein precipitation using methanol followed by additional sample clean up by turbulent flow liquid chromatography (TFLC). The sample was directly injected into the turbulent flow liquid chromatography tandem mass spectrometry system (TFLC-MS/MS) for online extraction followed by HPLC separation. The eluent was transferred to the mass spectrometer and ionized by heated electrospray negative ionization (HESI) and the analyte was quantified using a six-point calibration curve. The validated analytical measurement range (AMR) is 30-1,000 nMol/L. Dilutions of 10 and 200-fold were validated giving a clinical reportable range (CRR) of 30-200,000 nMol/L. The between-day and within-day imprecision values at concentrations spanning the AMR were less than 15%. This method was compared to an established LC-MS/MS method at a CLIA certified national reference laboratory and shows an excellent correlation with our TFLC-MS/MS method.

Sustained reflow in dogs with coronary thrombosis with K2P, a novel mutant of tissue-plasminogen activator.

Coronary artery reocclusion after thrombolysis with human recombinant tissue-type plasminogen activator (rt-PA) is related to the short half-life of this agent in plasma. K2P, a mutant of rt-PA lacking the fibronectin fingerlike, epidermal growth factor-like and first kringle domains (amino acids 6 to 173) and having the glycosylation site Asn184 mutagenized to Gln, has been produced in Chinese hamster ovary cells. In this study we compared the thrombolytic effect of K2P and rt-PA in dogs with electrically induced coronary artery thrombosis. Both agents were given intravenously in equimolar amounts over 20 min after the occlusive thrombus was stable for 30 min; dogs were monitored for 1 h after reperfusion if flow occurred. Coronary blood flow was restored by rt-PA in 6 (60%) of 10 dogs. The restored flow lasted for 49 +/- 12 min and mean flow at 60 min from the start of reperfusion was 7 +/- 3 ml/min. The reocclusion rate was 50% (three of six dogs). Flow was restored in five (100%) of five dogs by K2P. The restored blood flow lasted during the entire 1-h observation period in all but one dog and mean flow at 60 min was 49 +/- 16 ml/min (p less than 0.02 vs. flow in rt-PA-treated dogs). Restored coronary blood flow showed marked cyclic flow variations in rt-PA-treated but not in K2P-treated dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Standardization of procedures for ectopic marrow grafting: I. Influence of sex of recipient.

Bone marrow plugs implanted beneath the renal capsule of a normal syngeneic mouse recipient develop, within a few weeks, into a shell of marrow-containing bone. The marrow stromal microenvironment of the implant is reported to be of donor origin and therefore the technique has the potential for development into a quantitative assay of the stroma, or stroma-forming, capacity of the implanted marrow. A surprising difference has been shown, however, in that the female mouse does not permit the development of such an ectopic implant to the same extent as does a male recipient. The suppression of development of the implant is particularly dramatic when marrow from a male donor is implanted into a female recipient, but is strongly operative even upon donor marrow from a syngeneic female. The effect is partly strain dependent, being more pronounced in C57B1/6 and B6D2F1 mice than in DBA/2 or Balb/c. Castration and ovariectomy do not abrogate or modify the suppression. On the other hand, exposure of recipients to 6 Gy 137Cs gamma-radiation before implantation results in bigger implants developing in male recipients, and the suppressive effect of the female recipient upon the graft is reduced considerably or eliminated altogether. Marrow plugs were implanted into chimeras made by transplanting marrow from syngeneic male or female donors, i.e., into heavily irradiated B6D2F1 mice of the same or opposite sex. In female mice repopulated with marrow cells from male donors, the ectopic implants contained 2-3 times as many spleen colony-forming units (CFU-S) as did those in female mice populated by female marrow cells. Ectopic implants into male mice repopulated with female marrow cells contained fewer CFU-S than implants into male recipients having a male marrow, though the differences are smaller than those found in female recipients and may not be significant.

Measurement of erythropoiesis by radio-iron incorporation: influence of iron- and cell kinetic changes.

59Fe blood appearance curves have been obtained in mice by injection of the isotope at various times after 850 rad whole body X-irradiation and bone marrow grafting in order to produce different levels of erythropoiesis. The results demonstrate that measurements at 24, 48 and 72 hours are not comparable and lead to different interpretations. Standardization of the time at which 59Fe uptake measurements are made is therefore recommended.

Ectopic implantation studies using Sl/Sld marrow and recipients.

Marrow from Sl/Sld mice (in which the hemopoietic stromal microenvironment is defective), when implanted beneath the renal capsule of a normal littermate, produces an ectopic marrow site containing the same number of stem cells (CFU-S) and nearly as many GM-CFC as that obtained by implanting marrow from a normal littermate. On the other hand, a marrow plug from an Sl/Sld donor implanted beneath the renal capsule of an Sl/Sld littermate produces less than half the number of CFU-S and about 10% of the number of GM-CFC. This suggests that the recipient of the ectopic implant can contribute in some way to the stromal environment of the grafted marrow.

Development of spleen CFU-S colonies from day 8 to day 11: relationship to self-renewal capacity.

To investigate the persistence of spleen colonies from day 8 to day 11 of their development, we injected low numbers of marrow cells in order to obtain single colonies on the spleens of irradiated mice. Colonies were isolated on either half of the spleen on the eighth day. The position of day-11 colonies, determined relative to the ligature, indicated where novel colonies appear between those times. The results showed no evidence of the persistence of colonies from day 8 to day 11. The self-reproduction capacity of CFU-S that survive various cytotoxic drugs depends on the specific subpopulations that are affected by the drug. Using cyclophosphamide, busulphan, or BCNU, the self-renewal capacity of surviving CFU-S was manipulated. The results show that after cytotoxic treatments, a high day-11-day-8 ratio is not necessarily a reflection of a high self-renewal capacity of the CFU-S population that forms the day-11 colonies.

Standardization of procedures for ectopic marrow grafting. II. Influence on recipients of radiation dose and field size.

The ectopic implantation of mouse marrow to the kidney capsule offers considerable scope as an assay of the hemopoietic microenvironment. Our previous work has shown that whole-body irradiation of the graft recipient prior to implantation results in superior ossicle formation in the kidney of the host. Here we report that a range of irradiation doses over a 4-Gy threshold are equivalent with respect to conditioning the graft recipient. We also show that two distinct and separable influences affect graft growth in the irradiated recipient, namely, a local effect brought about in the irradiated kidney (and restricted to it) and secondly, a systemic effect resulting from irradiation of sites other than the kidney, which nevertheless affects ossicle growth in the shielded renal capsule.

On the late seeding of CFU-S to the spleen: 8- vs 12-day CFU-S.

Marrow from 5-fluorouracil- or cyclophosphamide-treated mice, injected into lethally irradiated recipients, gives an increasing number of spleen colonies between days 7 and 14. It has been suggested that the later-forming colonies result from the more primitive spleen colony-forming units (CFU-S), which first seed into the marrow, only later to be recirculated and form colonies in the spleen. Strontium 89 (89Sr), a bone-seeking radionuclide, was injected into recipient mice to block such putative recirculation. A dose of 89Sr, which killed at least 99.8% of CFU-S in, or entering, the bone cavities, was incapable of preventing the increase in spleen colony numbers. Similarly, the splenic environment, modified by the presence of spleen colonies and able to provide a better bed for trapping CFU-S from the peripheral circulation, yielded the same number of further CFU-S, whether or not the animal had received 89Sr. Thus, it was concluded that the 12-day CFU-S does not seed initially into the marrow spaces. Direct observation of the quality of CFU-S initially seeding into the bone marrow and spleen showed, by retransplantation into secondary irradiated mice, that a similar spectrum of CFU-S types had seeded both organs.

Comparison of haemopoiesis in young and old mice.

Haemopoietic status and functions have been compared in young (2-3-month-old) and old (2-2.5-year-old) BDF1 mice. The parameters measured include total marrow cellularity, CFU-S, CFU-mix, GM-CFC, BFU-E and CFU-F. In all cases the numbers of these cells in the femoral marrow of the old mice was equal to or greater than those in the femoral marrow of young mice. In addition to these parameters we have compared the ability of marrow from young and old mice to repopulate the marrow of recipient mice whose marrow had been eliminated by radiation; to grow in long-term bone marrow cultures; to produce ectopic grafts of marrow beneath the renal capsule of normal recipients; and to supply inhibitor and stimulator of stem cell proliferation in the marrow and to resynthesise these substances. We could detect no differences in any of these functions with the exception of that of resynthesis of the stem cell regulator substances, which appears to be somewhat slower in the old mice. This, however, does not impose any limitation upon the ability of the marrow to function either under normal conditions or in conditions requiring rapid proliferation. Therefore we can find no evidence whatsoever to suggest that aging of the haemopoietic system plays any part in aging of the individual or influencing the life-span.