Measurement of Cellular Immune Function of Breast Milk and Health Education of Pregnant and Lying in Women

Breast milk is different from any nutritional substitutes. Breast milk has biological specificity. The most irreplaceable nutrient for newborns is breast milk. In order to determine the immunoprotective effect of breast milk on newborns, 30 primiparas were selected to obtain a little milk before feeding in three different periods, which were divided into colostrum, transitional milk and mature milk. The contents of CD3, CD4, CD8, SlgA, IgG and IgM positive cells in nuclear cells were observed by inverted fluorescence microscope. The contents of IL-8, IFN - γ, and potassium, sodium, chlorine, calcium, magnesium and phosphorus in different time periods were compared between six groups. The results showed that the content of IFN - γ cells in colostrum was 1.61 and that of IL-8 cells was 0.83. However, the contents of IFN - γ cells and IL-8 cells in colostrum decreased to 0.31 and 0.36 at the time of transition milk. Therefore, breastfeeding from the third to the fifth day after delivery can give more immune cells to the newborn, which is conducive to the establishment of their own immune system. Therefore, in the teaching of health-related knowledge to pregnant women, we should advocate more maternal breastfeeding newborns, for the health of the newborn.

Template Theories, the Rule of Parsimony, and Disregard for Irreproducibility—The Example of Linus Pauling’s Research on Antibody Formation

In 1940, Linus Pauling proposed his template theory of antibody formation, one of many such theories that rejected Paul Ehrlich’s selective theory of preformed “receptors” (antibodies), assuming instead a direct molding of antibody shapes onto that of the antigen. Pauling believed that protein shapes—independently of amino acid sequences—determined antibody specificity and biological specificity in general. His theory was informed by his pioneering work on protein structure, and it was inspired by the intuitive “rule of parsimony” and simplicity. In 1942, Pauling published his alleged success in producing specific artificial antibodies through experiments based on his 1940 theory. However, his experiments could not be reproduced by prominent immunochemists at the time, and, later, it became generally accepted that antibody specificity was not generated according to Pauling’s and others’ “instruction” template theories. A citation analysis shows that Pauling’s papers on antibody generation continue to be cited as, among other things, pioneering studies of a chemical technology called “molecular imprinting.” The examples of Pauling and other protein chemists are used in this paper to demonstrate that scientific belief, philosophical concepts, and subjective theory preferences facilitated the occurrence of irreproducibility in immunochemistry and beyond. The article points to long-term consequences for the scientific community if irreproducible results are not acknowledged. It concludes by arguing that despite the risks, e.g., for the occurrence and perpetuation of irreproducible results that they entail, subjectivity and a commitment to scientific convictions have often been pre-requisites for the generation, and holding on to, scientific innovation in the face of doubt and rejection from the scientific community.

Whole-Brain Imaging of Subvoxel T1-Diffusion Correlation Spectra in Human Subjects

T1 relaxation and water mobility generate eloquent MRI tissue contrasts with great diagnostic value in many neuroradiological applications. However, conventional methods do not adequately quantify the microscopic heterogeneity of these important biophysical properties within a voxel, and therefore have limited biological specificity. We describe a new correlation spectroscopic (CS) MRI method for measuring how T1 and mean diffusivity (MD) co-vary in microscopic tissue environments. We develop a clinical pulse sequence that combines inversion recovery (IR) with single-shot isotropic diffusion encoding (IDE) to efficiently acquire whole-brain MRIs with a wide range of joint T1-MD weightings. Unlike conventional diffusion encoding, the IDE preparation ensures that all subvoxel water pools are weighted by their MDs regardless of the sizes, shapes, and orientations of their corresponding microscopic diffusion tensors. Accordingly, IR-IDE measurements are well-suited for model-free, quantitative spectroscopic analysis of microscopic water pools. Using numerical simulations, phantom experiments, and data from healthy volunteers we demonstrate how IR-IDE MRIs can be processed to reconstruct maps of two-dimensional joint probability density functions, i.e., correlation spectra, of subvoxel T1-MD values. In vivo T1-MD spectra show distinct cerebrospinal fluid and parenchymal tissue components specific to white matter, cortical gray matter, basal ganglia, and myelinated fiber pathways, suggesting the potential for improved biological specificity. The one-dimensional marginal distributions derived from the T1-MD correlation spectra agree well with results from other relaxation spectroscopic and quantitative MRI studies, validating the T1-MD contrast encoding and the spectral reconstruction. Mapping subvoxel T1-diffusion correlations in patient populations may provide a more nuanced, comprehensive, sensitive, and specific neuroradiological assessment of the non-specific changes seen on fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted MRIs (DWIs) in cancer, ischemic stroke, or brain injury.

Advances in the Regulation of Mammalian Follicle-Stimulating Hormone Secretion

Mammalian reproduction is mainly driven and regulated by the hypothalamic-pituitary-gonadal (HPG) axis. Follicle-stimulating hormone (FSH), which is synthesized and secreted by the anterior pituitary gland, is a key regulator that ultimately affects animal fertility. As a dimeric glycoprotein hormone, the biological specificity of FSH is mainly determined by the β subunit. As research techniques are being continuously innovated, studies are exploring the underlying molecular mechanism regulating the secretion of mammalian FSH. This article will review the current knowledge on the molecular mechanisms and signaling pathways systematically regulating FSH synthesis and will present the latest hypothesis about the nuclear cross-talk among the various endocrine-induced pathways for transcriptional regulation of the FSH β subunit. This article will provide novel ideas and potential targets for the improved use of FSH in livestock breeding and therapeutic development.

Were Ancestral Proteins Less Specific?

Some have hypothesized that ancestral proteins were, on average, less specific than their descendants. If true, this would provide a universal axis along which to organize protein evolution and suggests that reconstructed ancestral proteins may be uniquely powerful tools for protein engineering. Ancestral sequence reconstruction studies are one line of evidence used to support this hypothesis. Previously, we performed such a study, investigating the evolution of peptide-binding specificity for the paralogs S100A5 and S100A6. The modern proteins appeared more specific than their last common ancestor (ancA5/A6), as each paralog bound a subset of the peptides bound by ancA5/A6. In this study, we revisit this transition, using quantitative phage display to measure the interactions of 30,533 random peptides with human S100A5, S100A6, and ancA5/A6. This unbiased screen reveals a different picture. While S100A5 and S100A6 do indeed bind to a subset of the peptides recognized by ancA5/A6, they also acquired new peptide partners outside of the set recognized by ancA5/A6. Our previous work showed that ancA5/A6 had lower specificity than its descendants when measured against biological targets; our new work shows that ancA5/A6 has similar specificity to the modern proteins when measured against a random set of peptide targets. This demonstrates that altered biological specificity does not necessarily indicate altered intrinsic specificity, and sounds a cautionary note for using ancestral reconstruction studies with biological targets as a means to infer global evolutionary trends in specificity.

Glycoprotein hormone receptors (version 2020.4) in the IUPHAR/BPS Guide to Pharmacology Database

Glycoprotein hormone receptors (provisional nomenclature [45]) are activated by a non-covalent heterodimeric glycoprotein made up of a common α chain (glycoprotein hormone common alpha subunit CGA, P01215), with a unique β chain that confers the biological specificity to FSH, LH, hCG or TSH. There is binding cross-reactivity across the endogenous agonists for each of the glycoprotein hormone receptors. The deglycosylated hormones appear to exhibit reduced efficacy at these receptors [120].

Were ancestral proteins less specific?

Some have hypothesized that ancestral proteins were, on average, less specific than their descendants. If true, this would provide a universal axis along which to organize protein evolution and suggests that reconstructed ancestral proteins may be uniquely powerful tools for protein engineering. Ancestral sequence reconstruction studies are one line of evidence used to support this hypothesis. Previously, we performed such a study, investigating the evolution of peptide binding specificity for the paralogs S100A5 and S100A6. The modern proteins appeared more specific than their last common ancestor (ancA5/A6), as each paralog bound a subset of the peptides bound by ancA5/A6. In the current study, we revisit this transition, using quantitative phage display to measure the interactions of 19,194 random peptides with human S100A5, S100A6, and ancA5/A6. This unbiased screen reveals a different picture. While S100A5 and S100A6 do indeed bind to a subset of the peptides recognized by ancA5/A6, they also acquired new peptide partners outside of the set recognized by ancA5/A6. Our previous work showed that ancA5/A6 had lower specificity than its descendants when measured against biological targets; our new work shows that ancA5/A6 has similar specificity to the modern proteins when measured against a random set of peptide targets. This demonstrates that altered biological specificity does not necessarily indicate altered intrinsic specificity, and sounds a cautionary note for using ancestral reconstruction studies with biological targets as a means to infer global evolutionary trends in specificity.