Yersinia Enterocolitica

An intragastric inoculation of approx. 2 × 1010 Yersinia enterocolitica cells killed chinchillas in three days in the case of four strains out of six tested. Because of the sensitivity of chinchillas to this bacterium, the test is useful for the evaluation of the virulence and invasiveness of Y. enterocolitica isolates. This animal model could also be used for studies on the mechanism of the infection.     

A quantitative assay for collagen synthesis in microwell fibroblast cultures.

A new method for estimating collagen synthesis in microwell cultures of fibroblasts is presented, ³H-Labeled-proline-collagen was purified by successive salt precipitations at acid and neutral pH in the presence of carrier collagen. Variability between replicates was less than 10% (standard deviation) and recovery of labeled collage internal standards was greater than 90%. More than 90% of recoverable radioactivity was in collagen as demonstrated by polyacrylamide gel electrophoresis and carboxymethyl cellulose chromatography. The culture system is highly reproducible and allows use of a large number of separate cultures with uniformity of culture conditions and economy of reagents.     

Subcellular structures involved in internalization and degradation of epidermal growth factor

Epidermal Growth Factor (EGF), a small polypeptide which acts as a mitogen for many cell types, has previously been shown to bind to a specific plasma membrane receptor on 3T3 cells. If ¹²⁵I-EGF is bound to 3T3 cells for one hour at 4°C, it remains predominantly associated with the plasma membrane-containing fractions obtained by subjecting cell supernatants to equilibrium sedimentation on sucrose gradients. When binding is followed by a 10-minute incubation at 37°C, over 50% of the ¹²⁵I-EGF is associated with two internal membrane-containing peaks having higher densities than the plasma membrane. After one hour at 37°C, over 80% of the ¹²⁵I-EGF is degraded and removed from the cells. The most rapidly labeled internal peak corresponds in density to brain-coated vesicles (CVs). Antiserum prepared against coated vehicles from brain precipitates the ¹²⁵I-EGF in this peak. In addition, CVs containing ¹²⁵I-EGF can be co-purified from 3T3 cells exposed to ¹²⁵I-EGF, using brain as a carrier. Several lines of evidence suggest that the other ¹²⁵I-EGF-labeled intracellular peak is ¹²⁵I-EGF in lysosomes. These results provide kinetic and biochemical evidence for a unidirectional pathway for EGF catabolism by 3T3 cells. EGF first binds to the plasma membrane bound receptors, is then moved to the cytoplasm in CVs, and finally appears in lysosomes, where it is degraded and released from the cells. Ten-millimolar NH₄Cl blocks lysosomal hydrolysis of EGF almost completely. Subsequently, EGF internalization is inhibited. This finding suggests that the pathway for EGF internalization and degradation is tightly coupled.     

Lignin peroxidase from Phanerochaete chrysosporium. Molecular and kinetic characterization of isozymes

Five isozymes of lignin peroxidase from Phanerochaete chrysosporium were purified and their physical, molecular and kinetic properties determined. The isozymes differ from each other in terms of their isoelectric point, molecular mass, sugar content, spectral characteristics, substrate specificity and stability. The N-terminal sequence of amino acids was different for each isozyme suggesting they are different gene products. The isozyme with the highest carbohydrate level was most sensitive to changes in environmental factors. The kinetic behaviour of the isozymes varied clearly when tert-butyl hydroperoxide instead of hydrogen peroxide was used as the oxidant. Two out of five isozymes had very similar substrate specificity. The results are discussed in relation to the role which lignin peroxidase isozymes may play in lignin biodegradation.     

Enterotoxigenicity of Staphylococcus aureus strains isolated from poultry: raw poultry carcases as a potential food-poisoning hazard

Staphylococcus aureus strains were isolated from end-of-lay poultry carcases obtained from a plant at two different stages of processing before and after storage at different temperatures. These strains were supplemented with Staph. aureus strains isolated from poultry from a wide range of sources and biotyped, phage typed, and tested for production of enterotoxins A-E. The isolates were found to consist of poultry and human specific strains and each of these groups contained strains able to produce enterotoxin. Poultry strains produced only enterotoxin D whereas human strains produced enterotoxins A, C and D. The hen carcases used in storage experiments were found to be naturally contaminated with enterotoxin D producing staphylococci. No enterotoxin D could be detected on any of the carcases even after storage at temperatures which allowed multiplication of the organisms to occur (final Staph. aureus counts ranged from 10² to 10⁷/16 cm² of breast skin).     

Evolutionary inference from genomic data

The rapid accumulation of gene sequence data is allowing evolutionary inferences of unprecedented resolution. In the area of population genetics, gene trees and polymorphism data are being used to study demographic parameters. In the area of comparative biology, the shapes of phylogenetic trees provide information about patterns of speciation, coevolution, and macroevolution. A variety of statistical methods have been developed for exploiting the information contained within organismal genomes. In this paper, we emphasise the conceptual bases of the tests, rather than details of their implementation. BioEssays 1999;21:148–156. © 1999 John Wiley & Sons, Inc.     

The global gap in treatment coverage for major depressive disorder in 84 countries from 2000–2019: A systematic review and Bayesian meta-regression analysis

BackgroundThe treatment coverage for major depressive disorder (MDD) is low in many parts of the world despite MDD being a major contributor to disability globally. Most existing reviews of MDD treatment coverage do not account for potential sources of study-level heterogeneity that contribute to variation in reported treatment rates. This study aims to provide a comprehensive review of the evidence and analytically quantify sources of heterogeneity to report updated estimates of MDD treatment coverage and gaps by location and treatment type between 2000 and 2019.Methods and findingsA systematic review of the literature was conducted to identify relevant studies that provided data on treatment rates for MDD between January 1, 2000, and November 26, 2021, from 2 online scholarly databases PubMed and Embase. Cohort and cross-sectional studies were included if treatment rates pertaining to the last 12 months or less were reported directly or if sufficient information was available to calculate this along with 95% uncertainty intervals (UIs). Studies were included if they made use of population-based surveys that were representative of communities, countries, or regions under study. Studies were included if they used established diagnostic criteria to diagnose cases of MDD. Sample and methodological characteristics were extracted from selected studies. Treatment rates were modeled using a Bayesian meta-regression approach and adjusted for select covariates that quantified heterogeneity in the data. These covariates included age, sex, treatment type, location, and choice of MDD assessment tool. A total of 149 studies were included for quantitative analysis. Treatment coverage for health service use ranged from 51% [95% UI 20%, 82%] in high-income locations to 20% [95% UI 1%, 53%] in low- and lower middle-income locations. Treatment coverage for mental health service use ranged from 33% [95% UI 8%, 66%] in high-income locations to 8% [95% UI <1%, 36%] in low- and lower middle-income countries. Minimally adequate treatment (MAT) rates ranged from 23% [95% UI 2%, 55%] in high-income countries to 3% [95% UI <1%, 25%]) in low- and lower middle-income countries. A primary methodological limitation was the lack of sufficient data from low- and lower middle-income countries, which precluded our ability to provide more detailed treatment rate estimates.ConclusionsIn this study, we observed that the treatment coverage for MDD continues to be low in many parts of the world and in particular in low- and lower middle-income countries. There is a continued need for routine data collection that will help obtain more accurate estimates of treatment coverage globally.

In a systematic review and Bayesian meta-regression analysis, Modhurima Moitra and colleagues estimate major depressive disorder treatment coverage in 84 countries.     

Untapped potential of physiology,behaviour and immune markers to predict range dynamics and marginality

Linking environmental conditions to the modulators of individual fitness is necessary to predict long‐term population dynamics, viability, and resilience. Functional physiological, behavioral, and reproductive markers can provide this mechanistic insight into how individuals perceive physiological, psychological, chemical, and physical environmental challenges through physiological and behavioral responses that are fitness proxies. We propose a Functional Marginality framework where relative changes in allostatic load, reproductive health, and behavior can be scaled up to evidence and establish causation of macroecological processes such as local extirpation, colonization, population dynamics, and range dynamics. To fully exploit functional traits, we need to move beyond single biomarker studies to develop an integrative approach that models the interactions between extrinsic challenges, physiological, and behavioral pathways and their modulators. In addition to providing mechanistic markers of range dynamics, this approach can also serve as a valuable conservation tool for evaluating individual‐ and population‐level health, predicting responses to future environmental change and measuring the impact of interventions. We highlight specific studies that have used complementary biomarkers to link extrinsic challenges to population performance. These frameworks of integrated biomarkers have untapped potential to identify causes of decline, predict future changes, and mitigate against future biodiversity loss.     

Molecular dynamics simulations of small DNA plasmids: Effects of sequence and supercoiling on intramolecular motions

Small (600 base pair) DNA plasmids were modeled with a simplified representation (3DNA) and the intramolecular motions were studied using molecular mechanics and molecular dynamics techniques. The model is detailed enough to incorporate sequence effects. At the same time, it is simple enough to allow long molecular dynamics simulations. The simulations revealed that large-scale slithering occurs in a homogeneous sequence. In a heterogeneous sequence, containing numerous small intrinsic curves, the centers of the curves are preferentially positioned at the tips of loops. With more curves than loop tips (two in unbranched supercoiled DNA), the heterogeneous sequence plasmid slithers short distances to reposition other curves into the loop tips. However, the DNA is immobilized most of the time, with the loop tips positioned over a few favored curve centers. Branching or looping also appears in the heterogeneous sequence as a new method of repositioning the loop tips. Instead of a smooth progression of increasing writhing with increasing linking difference, theoretical studies have predicted that there is a threshold between unwrithed and writhed DNA at a linking difference between one and two. This has previously been observed in simulations of static structures and is demonstrated here for dynamic homogeneous closed DNA. Such an abrupt transition is not found in the heterogeneous sequence in both the static and dynamic cases. © 1996 John Wiley & Sons, Inc.