STIMULATION BY MINERAL AND FATTY ACIDS IN THE BARNACLE BALANUS BALANOIDES

1. Stimulation in the rock barnacle Balanus balanoides by hydrochloric, sulfuric, and nitric acids, and by the first seven members of the normal aliphatic acid series has been studied. The hydrogen ion concentrations of the solutions tested varied from 3.2 x 10^–8 to 5.889 x 10^–6. The criterion of response was percentage closure in groups of individuals, recorded at 1 minute intervals until maximum closure occurred. 2. The intensity of stimulation by these acids is proportional to the effects of two forces, one related to the change in the (H⁺), and the other to the field of force around the anion of the acid added to the environment. 3. A preliminary interpretation of the results led to the development of the following expression which fits approximately the data obtained at the end of 4 minutes: Per cent closure = 100 – 100e ^{–0.1z+(0.003125)2–0.1z+(0.003125)2n(z–0.4)} where z is the (H⁺) x 10⁷ and n is the number of carbon atoms (if present) in the anion of the acid. This equation assumes that the anions of the mineral acids enter into the reaction stoichiometrically, and emphasizes the difference in the fields of force around the anion of the fatty acids, a difference which is correlated with the length of the carbon chain. 4. A further analysis of the data revealed the presence of three or more receptor groups which appeared to be differentially affected by forces originating from the anions of the acids. 5. The order of stimulating efficiency for the mineral acids was found to be: HCl>H₂SO₄>HNO₃. 6. The order of stimulating efficiency for the fatty acids was found to be: heptylic>caproic>valeric>butyric = acetic>propionic = formic.     

Pleiotropic Mutations at the TUP1 Locus That Affect the Expression of Mating-Type-Dependent Functions in SACCHAROMYCES CEREVISIAE

The umr7–1 mutation, previously identified in a set of mutants that had been selected for defective UV-induced mutagenesis at CAN1, affects other cellular functions, including many of those regulated by the mating-type locus (MAT) in heterothallic Saccharomyces cerevisiae. The recessive umr7–1 allele, mapping approximately 20 cM distal to thr4 on chromosome III, causes clumpy growth in both a and α cells and has no apparent effect on a mating functions. However, α umr7 meiotic segregants fail to express several α-specific functions (e.g., high-frequency conjugation with a strains, secretion of the hormone α-factor and response to the hormone a-factor). In addition, α umr7 cells exhibit some a-specific characteristics, such as the barrier phenotype (Bar⁺) that prevents diffusion of α-factor and an increased mating frequency with α strains. The most striking property of α umr7 strains is their altered morphology, in which mitotic cells develop an asymmetric pear shape, like that of normal a cells induced to form "shmoos" by interaction with α-factor. Some a/α-specific diploid functions are also affected by umr7; instead of polar budding patterns, a/α umr7/umr7 diploids have medial budding like a/a, α/α and haploid strains. Moreover, a/α umr7/umr7 diploids have lost the ability to sporulate and are Bar⁺ like a or a/a strains. Revertant studies indicate that umr7–1 is a single point mutation. The umr7 mutant fails to complement mutants of both tup1 (selected for deoxythymidine monophosphate utilization) and cyc9 (selected for high iso-2-cytochrome c levels), and all three isolates have similar genetic and phenotypic properties. It is suggested that the product of this gene plays some common central role in the complex regulation of the expression of both MAT-dependent and MAT-independent functions.     

AMPHOTERIC BEHAVIOR OF COMPLEX SYSTEMS : IV. NOTE ON THE ISOELECTRIC POINT AND IONIZATION CONSTANTS OF SULFANILIC ACID.

From the solubility minimum the value of the basic ionization constant of sulfanilic acid is shown to lie probably between the values 1.7 x 10^–15 and 3.2 x 10^–15. From solubility measurements the value of this same constant is shown to lie probably between 2.0 and 2.2 x 10^–15, and the isoelectric point of sulfanilic acid is thus at a cH of 0.056 or a pH of 1.25. From conductivity ratios the acid ionization constant of sulfanilic acid is shown to be 7.05 x 10^–4 at room temperature (21°C.). Calculations are made, from data published in preceding papers, of the ionization constants of glycine, K_a being 2.3 x 10^–10, and K_b being 2.2 x 10^–12.     

Skin lipids from Saudi Arabian birds

Skin lipids play an important role in the regulation of cutaneous water loss (CWL). Earlier studies have shown that Saudi desert birds exhibit a tendency of reduced CWL than birds from temperate environment due to adaptive changes in composition of their skin lipids. In this study, we used thin-layer chromatography (TLC) for separation and detection of non-polar and polar lipids from the skin of six bird species including sooty gull, brown booby, house sparrow, Arabian waxbill, sand partridge, and laughing dove. The lipids were separated and detected on Silica gel G coated TLC plates and quantified by using densitometric image analysis. Rf values of the non-polar lipids were as follows: cholesterol (0.29), free fatty acids (0.58), triacylglycerol (0.69), fatty acids methyl esters (0.84) and cholesterol ester (0.97). Rf values for the polar lipids were: cerebroside (0.42), ceramide (0.55) and cholesterol (0.73). The results showed the abundance of fatty acids methyl esters (47.75–60.46%) followed by triacylglycerol (12.69–24.14%). The remaining lipid compositions were as follows: cholesterol (4.09–13.18%), ceramide (2.18–13.27%), and cerebroside (2.53–12.81%). In conclusion, our findings showed that TLC is a simple and sensitive method for the separation and quantification of skin lipids. We also reported a new protocol for lipid extraction using the zirconia beads for efficient disruption of skin tissues. This study will help us better understand the role of skin lipids in adaptive physiology towards adverse climatic conditions.     

Prognostic Value of Overexpressed p16INK4a in Vulvar Cancer: A Meta-Analysis

Objective

This study aimed to examine the prognostic value of overexpressed p16^INK4a in vulvar cancer. Although the tumor suppressor p16^INK4a has been shown to be of prognostic value in a wide variety of cancers and precancerous lesions, its role in the vulvar cancer is still unclear.

Methods

All publications in English language on the association between p16^INK4a and clinicopathological features of vulvar cancer were searched from Pubmed, Embase, and Web of Science, and those in Chinese language were identified manually and online from the China National Knowledge Infrastructure. Strict inclusion and exclusion criteria were followed. Odds ratios(ORs) or risk ratios(RRs) with 95% confidence intervals(CIs) were pooled to assess the strength of association. Publication bias was estimated using funnel plots and the Egger’s regression test.

Results

A total of 17 studies with 2309 patients were included. The p16^INK4a overexpression was found to correlate significantly with the lower International Federation of Gynecology and Obstetrics stage(I+II vs III+IV; OR = 0.60,95%CI:0.41–0.86,P = 0.006),negative lymph node metastasis(negative vs positive; OR = 0.61,95%CI:0.39–0.95,P = 0.029),patient’s age<55(OR = 0.54,95%CI:0.31–0.96,P = 0.034),human papillomavirus–positive status(OR = 0.01,95%CI:0.00–0.11,P<0.001),and higher overall survival(RR = 0.53,95%CI = 0.35–0.80,P = 0.003).

Conclusion

The p16^INK4a might be associated with a higher survival and indicates better prognosis of vulvar cancer.     

STIMULATION BY THE MINERAL ACIDS,HYDROCHLORIC, SULFURIC,AND NITRIC,IN THE SUNFISH EUPOMOTIS

1. The stimulating efficiency of hydrochloric, sulfuric, and nitric acids has been measured in the sunfish Eupomotis gibbosus, by a method which reduces experimental errors to a minimum. 2. The results show that stimulation by these acids is primarily dependent upon the (H⁺) produced in the animal''s aquatic environment, and that the reaction time is a logarithmic function of the (H⁺) within the range tested expressed by the equation: (RT–5) = –4.3 log (H⁺ x 10⁴) + 9.118. 3. Any effect of the chloride, sulfate, and nitrate ions must itself be measured by the (H⁺). 4. Variation in the reaction time is also a logarithmic function of the (H⁺), and the percentage variation is independent of the (H⁺) over the range tested. 5. Freshly collected fish show a lower threshold for stimulation as determined by the (H⁺) than do fish adapted to laboratory conditions, but relatively the reaction times of the two groups are the same.     

THE BEHAVIOR OF THE NUCLEIC ACIDS DURING THE EARLY DEVELOPMENT OF THE SEA URCHIN EGG (ARBACIA)

The authors wish to correct an error in the paper "The behavior of the nucleic acids during the early development of the sea urchin egg (Arbacia)" (J. Gen. Physiol., 1947–48, 31, 203). Owing to an oversight, the figures for the amounts of various P fractions in a single Arbacia egg have been erroneously expressed in γ x 10^–3 units (Tables I and II, page 205; the last two lines of page 206). The figures should have been expressed in γ x 10^–5 units. Thus, the fertilized Arbacia egg contains an average of 20 γ x 10^–5 ribonucleic acid P and 0.7 to 1 γ x 10^–5 desoxyribonucleic acid P.     

THE APPARENT DISTORTION OF BRIEF RECTANGULAR ELECTRICAL STIMULI IN NERVE

If it is assumed that the kinetics of the process of excitation in nerve is given by dp/dt = KI – kp, I being the actual exciting component of the current, p the state of excitation, and K and k constants, it is necessary to postulate that on application of a rectangular stimulus of voltage, V, the current, I, undergoes a transient exponential variation, usually a decrease, in order that the integral of the differential equation (above) may fit the strength-duration data in V and t. This hypothesis is substantiated by data by Sakamoto on single fibers of the sciatic nerve of the frog. The time constant of the postulated current transient is of the order of 10^–4 sec. for single fibers and of the order of 10^–5 sec. or less in the sciatic nerve trunk. The latter value is about the same as that found by Cole in the same tissue by purely physical measurements. Some criticisms by Rushton (1934) are discussed.     

Variable Nav1.5 Protein Expression from the Wild-Type Allele Correlates with the Penetrance of Cardiac Conduction Disease in the Scn5a +/? Mouse Model

Background

Loss-of-function mutations in SCN5A, the gene encoding Na_v1.5 Na⁺ channel, are associated with inherited cardiac conduction defects and Brugada syndrome, which both exhibit variable phenotypic penetrance of conduction defects. We investigated the mechanisms of this heterogeneity in a mouse model with heterozygous targeted disruption of Scn5a (Scn5a ^+/− mice) and compared our results to those obtained in patients with loss-of-function mutations in SCN5A.

Methodology/Principal Findings

Based on ECG, 10-week-old Scn5a ^+/− mice were divided into 2 subgroups, one displaying severe ventricular conduction defects (QRS interval>18 ms) and one a mild phenotype (QRS≤18 ms; QRS in wild-type littermates: 10–18 ms). Phenotypic difference persisted with aging. At 10 weeks, the Na⁺ channel blocker ajmaline prolonged QRS interval similarly in both groups of Scn5a ^+/− mice. In contrast, in old mice (>53 weeks), ajmaline effect was larger in the severely affected subgroup. These data matched the clinical observations on patients with SCN5A loss-of-function mutations with either severe or mild conduction defects. Ventricular tachycardia developed in 5/10 old severely affected Scn5a ^+/− mice but not in mildly affected ones. Correspondingly, symptomatic SCN5A–mutated Brugada patients had more severe conduction defects than asymptomatic patients. Old severely affected Scn5a ^+/− mice but not mildly affected ones showed extensive cardiac fibrosis. Mildly affected Scn5a ^+/− mice had similar Na_v1.5 mRNA but higher Na_v1.5 protein expression, and moderately larger I_Na current than severely affected Scn5a ^+/− mice. As a consequence, action potential upstroke velocity was more decreased in severely affected Scn5a ^+/− mice than in mildly affected ones.

Conclusions

Scn5a ^+/− mice show similar phenotypic heterogeneity as SCN5A-mutated patients. In Scn5a ^+/− mice, phenotype severity correlates with wild-type Na_v1.5 protein expression.     

THE DIFFUSION OF CARBON DIOXIDE IN TISSUES

1. Two methods are given for measuring the rate of diffusion of CO₂ in tissue membranes. Methods are also given for the determination of tissue thickness and the absorption coefficient for CO₂ in tissues. 2. The values obtained for the permeability constant (P x 10⁴) at 22°C. for CO₂ in the following tissues are:—frog skin, 3.05; connective tissue (dog), 2.65; smooth muscle (cat), 5.00; frog muscle, 5.29; striated muscle (dog), 4.70. P is expressed as cc. per cm.² per minute under a pressure gradient of one atmosphere per cm. 3. Evidence is presented to show that in a "steady state" bicarbonate contributes a negligible amount to the diffusion of CO₂. 4. The absorption coefficient for CO₂ in frog skin is 0.73 cc. per cc. and for frog muscle 0.78 cc. per cc. 5. In all of the tissues studied the diffusion of CO₂ is slower than in water. The diffusion coefficients (K x 10⁴ in cm.²/minute) at 22°C. for tissues as compared with water are:—water (16°C.), 9.5 (Hüfner, 1897); frog skin, 4.1; connective tissue, 3.7; frog muscle, 6.8; striated muscle (dog), 6.0; smooth muscle (cat), 6.4. 6. The time course of saturation of a tissue with CO₂ is altered in the presence of available base. Non-acidified tissues saturate more slowly than acidified tissues and the rate of saturation is dependent on the CO₂ tension.     

Successive Mineralization and Detoxification of Benzo[a]pyrene by the White Rot Fungus Bjerkandera sp. Strain BOS55 and Indigenous Microflora

White rot fungi can oxidize high-molecular-weight polycyclic aromatic hydrocarbons (PAH) rapidly to polar metabolites, but only limited mineralization takes place. The objectives of this study were to determine if the polar metabolites can be readily mineralized by indigenous microflora from several inoculum sources, such as activated sludge, forest soils, and PAH-adapted sediment sludge, and to determine if such metabolites have decreased mutagenicity compared to the mutagenicity of the parent PAH. ¹⁴C-radiolabeled benzo[a]pyrene was subjected to oxidation by the white rot fungus Bjerkandera sp. strain BOS55. After 15 days, up to 8.5% of the [¹⁴C]benzo[a]pyrene was recovered as ¹⁴CO₂ in fungal cultures, up to 73% was recovered as water-soluble metabolites, and only 4% remained soluble in dibutyl ether. Thin-layer chromatography analysis revealed that many polar fluorescent metabolites accumulated. Addition of indigenous microflora to fungal cultures with oxidized benzo[a]pyrene on day 15 resulted in an initially rapid increase in the level of ¹⁴CO₂ recovery to a maximal value of 34% by the end of the experiments (>150 days), and the level of water-soluble label decreased to 16% of the initial level. In fungal cultures not inoculated with microflora, the level of ¹⁴CO₂ recovery increased to 13.5%, while the level of recovery of water-soluble metabolites remained as high as 61%. No large differences in ¹⁴CO₂ production were observed with several inocula, showing that some polar metabolites of fungal benzo[a]pyrene oxidation were readily degraded by indigenous microorganisms, while other metabolites were not. Of the inocula tested, only PAH-adapted sediment sludge was capable of directly mineralizing intact benzo[a]pyrene, albeit at a lower rate and to a lesser extent than the mineralization observed after combined treatment with white rot fungi and indigenous microflora. Fungal oxidation of benzo[a]pyrene resulted in rapid and almost complete elimination of its high mutagenic potential, as observed in the Salmonella typhimurium revertant test performed with strains TA100 and TA98. Moreover, no direct mutagenic metabolite could be detected during fungal oxidation. The remaining weak mutagenic activity of fungal cultures containing benzo[a]pyrene metabolites towards strain TA98 was further decreased by subsequent incubations with indigenous microflora.     

PURIFIED DIPHTHERIA ANTITOXIN IN THE ULTRACENTRIFUGE AND IN THE ELECTROPHORESIS APPARATUS

Ultracentrifugation studies of diphtheria antitoxin showed that: 1. Purified antitoxin of high activity obtained from horse plasma without enzymatic treatment has exactly the same sedimentation constant as the globulin fraction obtained in a similar way from normal horse plasma s ₂₀ ^water = 6.9 x 10^–13. 2. Purified antitoxin obtained with trypsin digestion of the toxin-antitoxin complex has a sedimentation constant of s ₂₀ ^water = 5.5 ± 0.1 x 10^–13, a diffusion constant of D ₂₀ ^water = 5.7₆ x 10^–7, and a molecular weight of about 90,000. Electrophoresis experiments demonstrated that: 1. The trypsin-purified antitoxin has an isoelectric point not far from pH 7.0. 2. The reversible spreading noticed at about pH 7.3 cannot be attributed to heterogeneous preparation. 3. The large increase in the γ-globulin fraction occurring during immunization consists either of antitoxin of various degrees of activity or of some inert protein in addition to the antitoxin.     

Prognostic Significance of Overexpressed p16INK4a in Patients with Cervical Cancer: A Meta-Analysis

Background

p16^INK4a is a tumor suppressor protein which is induced in cells upon the interaction of high-risk HPV E7 with the retinoblastoma protein by a positive feedback loop, but cannot exert its suppressing effect. Previous reports suggested that p16^INK4a immunostaining allows precise identification of even small CIN or cervical cancer lesions in biopsies. The prognostic value of overexpressed p16^INK4a in cervical cancer has been evaluated for several years while the results remain controversial. We performed a systematic review and meta-analysis of studies assessing the clinical and prognostic significance of overexpression of p16^INK4a in cervical cancer.

Methods

Identification and review of publications assessing clinical or prognostic significance of p16^INK4a overexpression in cervical cancer until March 1, 2014. A meta-analysis was performed to clarify the association between p16^INK4a overexpression and clinical outcomes.

Results

A total of 15 publications met the criteria and comprised 1633 cases. Analysis of these data showed that p16^INK4a overexpression was not significantly associated with tumor TNM staging (I+II vs. III+IV) (OR = 0.75, 95% confidence interval [CI]: 0.35–1.63, P = 0.47), the tumor grade (G1+ G2 vs. G3) (OR = 0.78, 95% CI: 0.39–1.57, P = 0.49), the tumor size (<4 vs. ≥4 cm) (OR = 1.10, 95% CI: 0.45–2.69, P = 0.83), or vascular invasion (OR = 1.20, 95% CI: 0.69–2.08, P = 0.52). However, in the identified studies, overexpression of p16^INK4a was highly correlated with no lymph node metastasis (OR = 0.51, 95% CI: 0.28–0.95, P = 0.04), increased overall survival (relative risk [RR]: 0.42, 95% CI: 0.24–0.72, P = 0.002) and increased disease free survival (RR: 0.60, 95% CI: 0.44–0.82, P = 0.001).

Conclusions

This meta-analysis shows overexpression of p16^INK4a in cervical cancer is connected with increased overall and disease free survival and thus marks a better prognosis.     

Prediction and Testing of Biological Networks Underlying Intestinal Cancer

Colorectal cancer progresses through an accumulation of somatic mutations, some of which reside in so-called “driver” genes that provide a growth advantage to the tumor. To identify points of intersection between driver gene pathways, we implemented a network analysis framework using protein interactions to predict likely connections – both precedented and novel – between key driver genes in cancer. We applied the framework to find significant connections between two genes, Apc and Cdkn1a (p21), known to be synergistic in tumorigenesis in mouse models. We then assessed the functional coherence of the resulting Apc-Cdkn1a network by engineering in vivo single node perturbations of the network: mouse models mutated individually at Apc (Apc^1638N+/−) or Cdkn1a (Cdkn1a^−/−), followed by measurements of protein and gene expression changes in intestinal epithelial tissue. We hypothesized that if the predicted network is biologically coherent (functional), then the predicted nodes should associate more specifically with dysregulated genes and proteins than stochastically selected genes and proteins. The predicted Apc-Cdkn1a network was significantly perturbed at the mRNA-level by both single gene knockouts, and the predictions were also strongly supported based on physical proximity and mRNA coexpression of proteomic targets. These results support the functional coherence of the proposed Apc-Cdkn1a network and also demonstrate how network-based predictions can be statistically tested using high-throughput biological data.     

Stable Water Use Efficiency of Tibetan Alpine Meadows in Past Half Century: Evidence from Wool δ13C Values

Understanding the influences of climatic changes on water use efficiency (WUE) of Tibetan alpine meadows is important for predicting their long-term net primary productivity (NPP) because they are considered very sensitive to climate change. Here, we collected wool materials produced from 1962 to 2010 and investigated the long-term WUE of an alpine meadow in Tibet on basis of the carbon isotope values of vegetation (δ ¹³C_veg). The values of δ ¹³C_veg decreased by 1.34‰ during 1962–2010, similar to changes in δ ¹³C values of atmospheric CO₂. Carbon isotope discrimination was highly variable and no trend was apparent in the past half century. Intrinsic water use efficiency (W _i) increased by 18 μmol·mol^–1 (approximately 23.5%) during 1962–2010 because the increase in the intercellular CO₂ concentration (46 μmol·mol^–1) was less than that in the atmospheric CO₂ concentration (C _a, 73 μmol·mol^–1). In addition, W _i increased significantly with increasing growing season temperature and C _a. However, effective water use efficiency (W _e) remained relatively stable, because of increasing vapor pressure deficit. C _a, precipitation, and growing season temperature collectively explained 45% of the variation of W _e. Our findings indicate that the W _e of alpine meadows in the Tibetan Plateau remained relatively stable by physiological adjustment to elevated C _a and growing season temperature. These findings improve our understanding and the capacity to predict NPP of these ecosystems under global change scenarios.     

ON THE NATURE OF FORCES OPERATING IN BLOOD CLOTTING : I. THE PARTICIPATION OF ELECTROSTATIC ATTRACTION

The results of the study of the inhibiting effect of neutral salts upon the clotting tendency of fibrinogen by thrombin may be summarised as follows: Salts like NaCl and KCl inhibit only weakly. Salts of the same cation (K^•) with monovalent anions of different ionic radius are the more active the larger the anion (Cl'',Br'',I''). Salts of the same cation with anions of different valency are the more active the higher the charge of the anion (1–1 <1–2 <1–3 <1–4). Salts with the same anion with cations of different valency show stronger inhibition in the case of cations of higher charge (K^•,Na^• < Mg^••, Ca^••, Sr^••, Ba^••). Salts with the same anion and cations of the same charge, but of different radius, are the more active the larger the cation (but with an inversion between Mg^•• and Ca^•• in the series of the alkali earths, which is not infrequent in biocolloids). These results show that the clotting of fibrinogen with thrombin is, at least partly, caused by a coacervation process, due to electrostatic attraction between positive and negative groups. Its nature and localisation will be dealt with in the next paper of this series.     

Dependence on Mating Type for the Overproduction of Iso-2-Cytochrome c in the Yeast Mutant CYC7–H2

The CYC7–H2 mutation causes an approximately 20-fold overproduction of iso–2–cytochromo c in a and α haploid strains of the yeast Saccharomyces cerevisiae due to an alteration in the nontranslated regulatory region that is presumably contiguous with the structural region. In this investigation, we demonstrated that heterozygosity at the mating type locus, a/α or a/a/α/α, prevents expression of the overproduction, while homozygosity, a/a and α/α, and hemizygosity, a/0 and α/0, allow full expression of the CYC7–H2 mutation, equivalent to the expression observed in a and α haploid strains. There is no decrease in the overproduction of iso-2-cytochrome c in a/α diploid strains containing either of the other two similar mutations, CYC7–H1 and CYC7–H3. It appears as if active expression of one or another of the mating-type alleles is required for the overproduction of iso-2-cytochrome c in CYC7–H2 mutants.     

Cooperative polymerization of photosynthetic pigments in formamide-water solution

The aggregation of bacteriochlorophyll a and bacteriopheophytin a into large oligomers with maximum optical absorption at 860 nm was studied in a 3:1 (vol/vol) formamide/water solution, using optical absorption spectroscopy and electron microscopy. The aggregation is cooperative and proceeds according to two equilibrium constants. Initially, two pigment molecules form a “seed” that absorbs at ≈860 nm. The equilibrium constant, K_a, governing this reaction equals 1.3 × 10³ M^-1 in the case of bacteriochlorophyll a (due to experimental limitations, K_a for bacteriopheophytin a could not be determined). The addition of monomers to aggregates consisting of two or more units is governed by an equilibrium constant, K_b, equal to 2.2 × 10⁶ M^-1 for bacteriochlorophyll a and ≈ 10⁹ M^-1 for bacteriopheophytin a. The enthalpy and entropy changes that drive the bacteriochlorophyll oligomer formation are -9.25 and ≈0.0 kcal/mol, respectively. Above a threshold concentration, the amount of oligomers remains constant but their length continues to increase. Each oligomer appears to consist of dimers that are associated by hydrophobic interactions among their alcohol residues, forming long strands. Single strands presumably coil into helices that are seen as cylinders. The bacteriochlorophyll a oligomers form cylinders with a constant diameter of 150 Å and an average length of 2,000 Å (at 1.5 × 10^-5 M bacteriochlorophyll a). These cylinders contain 200-250 bacteriochlorophyll a dimers. The bacteriopheophytin oligomers coil into wider cylinders (≈400 Å in diameter) which contain ≈600-700 bacteriopheophytin a dimers. In both cases, the separation between the dimers is ≈20 Å. At such distances, the dipolar interactions among adjacent dimers are negligible and do not affect the optical absorption of each individual pair. Therefore, the optical absorption of these pairs can be a tool for investigating the absorption pattern of photosynthetic pigments in vivo.     

The Impact of PNPLA3 rs738409 Genetic Polymorphism and Weight Gain ≥10 kg after Age 20 on Non-Alcoholic Fatty Liver Disease in Non-Obese Japanese Individuals

Non-alcoholic fatty liver disease (NAFLD) in non-obese individuals is inadequately elucidated. We aim to investigate the impact of known genetic polymorphisms on NAFLD and the interaction between genetic risks and weight gain on NAFLD in obese and non-obese Japanese individuals. A total of 1164 participants who received health checkups were included. Participants with excessive alcohol consumption, with viral hepatitis or other inappropriate cases were excluded. Fatty liver was diagnosed by ultrasonography. Participants with a body mass index (BMI) of <18.5 kg/m², 18.5–22.9 kg/m², 23.0–24.9 kg/m² and ≥25 kg/m² were classified underweight, normal weight, overweight and obese, respectively. Self-administered questionnaire for lifestyle was assessed and a total of 8 previously reported genetic polymorphisms were chosen and examined. In all, 824 subjects were enrolled. The overall prevalence of NAFLD was 33.0%: 0% in underweight, 15.3% in normal weight, 41.1% in overweight and 71.7% in obese individuals. The prevalence of NAFLD is more affected by the G allele of patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 in normal weight (odds ratio (OR) 3.52; 95%-CI: 1.42–8.71; P = 0.0063) and in overweight individuals (OR 2.60; 95%-CI: 1.14–5.91; P = 0.0225) than in obese individuals (not significant). Moreover, the G allele of PNPLA3 rs738409 and weight gain ≥10 kg after age 20 had a joint effect on the risk of NAFLD in the normal weight (OR 12.00; 95% CI: 3.71–38.79; P = 3.3×10⁻⁵) and the overweight individuals (OR 13.40; 95% CI: 2.92–61.36; P = 0.0008). The G allele of PNPLA3 rs738409 is a prominent risk factor for NAFLD and the interaction between the PNPLA3 rs738409 and weight gain ≥10 kg after age 20 plays a crucial role in the pathogenesis of NAFLD, especially in non-obese Japanese individuals.