Study of the nature of lysosomes and of their acid phosphatase

Summary Treatment with M/2 CaCl₂ or fresh frozen sections of various organs of mice inhibits the subsequent histochemical demonstration of acid phosphatase by various procedures. This inhibition can be reversed by treatment with M/I NaCl. Fixation in cold formalin solution, or treatment with fat solvents weakens or abolishes this effect with the result that phosphatase staining is not markedly influenced by pretreatment with salts. The effect of surfactants in inhibiting acid phosphatase staining is diminished by fixation in formalin. Treatment with M/2 CaCl₂ of fresh frozen sections of mice organs partly inhibited the histochemical staining of phospholipids.The findings indicate that acid phosphatase molecules are bound to polar lipids and that under the influence of excess of Ca ions the lipoproteic molecules of acid phosphatase form droplets bounded by hydrophobic groups of the lipids. In such droplets the enzyme molecules are not available to act on substrates dissolved in the medium, and the droplets may be regarded as lysosomes. Under the influence of excess Na ions in the milieu the lipoprotein layer breaks into droplets bounded on the outside by the enzyme protein and the hydrophilic groups of the phospholipids. Such particles probably represent microsomes. The implications of these conclusions are discussed.A preliminary communication dealing with the present study has been published (in Hebrew) in the Harefuah (Wolman, 1964).     

Bearding the scorpion in his den: desert isopods take risks to validate their ‘landscape of fear’ assessment

Animals balance the risk of predation against other vital needs by adjusting their spatial behavior to match spatiotemporal variation in predation risk. To map this ‘landscape of fear’, prey use evolutionary rules of thumbs that are associated with the activity and hunting efficiency of predators. In addition, prey acquire perceptual information about the presence, identity and state of potential predators and use these cues to focus their acute anti‐predatory responses. Our goal was to explore if and how prey also use such perceptual information that decays with time to update their spatiotemporal risk assessment. We placed scorpions in freshly dug burrows and recorded the spatial activity and defense behavior of their isopod prey upon encountering the burrows straight after settling the scorpions and seven days later. To corroborate our understanding, we also examined the isopods’ detailed reactions towards deserted scorpion burrows. The isopods reacted defensively to scorpion burrows during their first encounter. After seven days, proportionally more isopods approached the scorpion burrows on their way out for foraging and fewer isopods encountered it on their way back. No changes in the spatial activity were observed towards deserted burrows. In addition, on the eighth day, more isopods entered the risky area near the scorpion burrows when leaving their own burrow than on the first encounter. The results suggest that isopods used predator cues to readjust the ‘landscape of fear’. Yet, rather than avoiding the dangerous areas altogether, the isopods implemented risky inspection behavior, validating whether the danger is actual. Our findings imply that inspection behavior toward predators can be used for future planning of prey spatial activity, offsetting possible ‘information decay costs’.     

Piromelatine decreases triglyceride accumulation in insulin resistant 3T3-L1 adipocytes: Role of ATGL and HSL

Piromelatine, a novel investigational multimodal sleep medicine, is developed for the treatment of patients with primary and co-morbid insomnia. Piromelatine has been shown to inhibit weight gain and improve insulin sensitivity in high-fat/high-sucrose-fed (HFHS) rats. Considering that piromelatine has also been implicated in lowering of triglyceride levels in HFHS rats, this work elucidated whether this effect involves in the regulation of adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) in triglyceride (TG) metabolism. In this study, we investigated the effects of piromelatine and MT2 receptors inhibition on TG content, insulin-stimulated glucose uptake, and the expressions of ATGL and HSL in 3T3-L1 adipocytes preincubated in high glucose and high insulin (HGI) conditions. Our results showed that culturing 3T3-L1 adipocytes under HGI conditions increased triglyceride accumulation with concomitant decrease of ATGL and HSL expression, inducing insulin resistance in 3T3-L1 adipocytes. We also found that triglyceride accumulation was significantly inhibited and the levels of ATGL/HSL increased after melatonin or piromelatine treatment. The effects of melatonin/piromelatine (10 nM) were counteracted by pretreatment with the relatively selective MT2 receptor antagonist luzindole (100 nM). In this study, our data demonstrate that piromelatine reverses high glucose and high insulin-induced triglyceride accumulation in 3T3-L1 adipocytes, possibly through up-regulating of ATGL and HSL expression via a melatonin-dependent manner.     

Childhood Chronic Physical Aggression Associates with Adult Cytokine Levels in Plasma

Background

An increasing number of animal and human studies are indicating that inflammation is associated with behavioral disorders including aggression. This study investigates the association between chronic physical aggression during childhood and plasma cytokine levels in early adulthood.

Methodology/Principal Findings

Two longitudinal studies were used to select males on a chronic physical aggression trajectory from childhood to adolescence (n = 7) and a control group from the same background (n = 25). Physical aggression was assessed yearly by teachers from childhood to adolescence and plasma levels of 10 inflammatory cytokines were assessed at age 26 and 28 years. Compared to the control group, males on a chronic physical aggression trajectory from childhood to adolescence had consistently lower plasma levels of five cytokines: lower pro-inflammatory interleukins IL-1α (T(28.7) = 3.48, P = 0.002) and IL-6 (T(26.9) = 3.76, P = 0.001), lower anti-inflammatory interleukin IL-4 (T(27.1) = 4.91, P = 0.00004) and IL-10 (T(29.8) = 2.84, P = 0.008) and lower chemokine IL-8 (T(26) = 3.69, P = 0.001). The plasma levels of four cytokines accurately predicted aggressive and control group membership for all subjects.

Conclusions/Significance

Physical aggression of boys during childhood is a strong predictor of reduced plasma levels of cytokines in early adulthood. The causal and physiological relations underlying this association should be further investigated since animal data suggest that some cytokines such as IL-6 and IL-1β play a causal role in aggression.     

Tuberculosis Incidence in HIV/AIDS Patients in Israel, 1983–2010

Objectives

People living with HIV/AIDS (PLWHA) who develop tuberculosis disease are at greater mortality-risk. This study aimed to assess tuberculosis disease incidence among all PLWHA in Israel and identify populations at high-risk for developing tuberculosis.

Design and Methods

Retrospective cohort-study based on the National HIV and Tuberculosis Registries, which were cross-matched and followed for the last 28-years. PLWHA who developed tuberculosis were compared to those who did not by the Cox-proportional analysis to generate hazard-ratios, and survival-analysis was performed by Log-Rank test.

Results

Of all the 6579 PLWHA reported between 1983 and 2010, corresponding to 55737 person-years, 384 (5.8%) developed tuberculosis. Of those, 14 were Israeli-born and 370 were non-Israeli born. The overall tuberculosis incidence-density was 6.9 cases/1000 person-years (95% CI 1.8–12.0). The cumulative tuberculosis-incidence among PLWHA in 2010 was 586 times higher than in HIV-negative individuals (3400 and 5.8 cases per 100000 population, respectively). Higher hazard-ratios to developing tuberculosis were found in migrant citizens PLWHA who were males, non-Israeli born, those who were diagnosed with HIV/AIDS after 1997, those who originated in high-tuberculosis prevalence country and those who acquired HIV by heterosexual or drug-injection transmission. PLWHA who developed tuberculosis had higher odds of dying than other PLWHA (36.5% and 16.6%, respectively, p<0.001, odds ratio = 2.8, 95% confidence-interval 2.3–3.6). In survival-analysis, time to develop tuberculosis was shorter among males than females, in PLWHA who were reported with HIV after 1997, in heterosexual who originated in high-tuberculosis countries, followed by injecting drug-users, heterosexual from low-tuberculosis burden countries and men who have sex with men.

Conclusion

Tuberculosis-incidence is higher among non-Israeli born PLWHA, with decreasing trends from 1991. Despite the moderate TB-rate disease among PLWHA, it remains an important cause for severe morbidity and mortality. Tuberculosis in PLWHA reflects mainly the tuberculosis-burden in the originating country and possibly also the mode of HIV-transmission.     

Reduced Ventricular Arrhythmogeneity and Increased Electrical Complexity in Normal Exercised Rats

Background

The mechanisms whereby aerobic training reduces the occurrence of sudden cardiac death in humans are not clear. We test the hypothesis that exercise-induced increased resistance to ventricular tachycardia and fibrillation (VT/VF) involve an intrinsic remodeling in healthy hearts.

Methods and Results

Thirty rats were divided into a sedentary (CTRL, n = 16) and two exercise groups: short- (4 weeks, ST, n = 7) and long-term (8 weeks, LT, n = 7) trained groups. Following the exercise program hearts were isolated and studied in a Langendorff perfusion system. An S₁–S₂ pacing protocol was applied at the right ventricle to determine inducibility of VT/VF. Fast Fourier transforms were applied on ECG time-series. In-vivo measurements showed training-induced increase in aerobic capacity, heart-to-body weight ratio and a 50% low-to-high frequency ratio reduction in the heart rate variability (p<0.05). In isolated hearts the probability for VF decreased from 26.1±14.4 in CTRL to 13.9±14.1 and 6.7±8.5% in the ST and LT, respectively (p<0.05). Duration of VF also decreased from 19.0±5.7 in CTRL to 8.8±7.1 and 6.0±5.8 sec in ST and LT respectively (p<0.05). Moreover, the pacing current required for VF induction increased following exercise (2.9±1.7 vs. 5.4±2.1 and 8.5±0.9 mA, respectively; p<0.05). Frequency analysis of ECG revealed an exercise-induced VF transition from a narrow single peak spectrum at 17 Hz in CTRL to a broader range of peaks ranging between 8.8 and 22.5 Hz in the LT group (p<0.05).

Conclusion

Exercise in rats leads to reduced VF propensity associated with an intrinsic cardiac remodeling related to a broader spectral range and faster frequency components in the ECG.     

Red gall pigmentation: cytokinin stimulation is not everything

Recently, the nature of gall pigmentation phenomenon has gained interest, with different, and often contradicting, explanations and hypotheses. A recent, welcome contribution by Connor et al. (Arthropod–Plant Interact 6:489–495, 2012) suggested that gall pigmentation is a mere “fabricational noise” of the gall development, caused by the production of anthocyanin due to the accumulation of cytokinins and sugars. We propose that this perspective, although probably true in some systems, is an oversimplification of a more complex situation. We argue that since multiple pigments are likely to be involved in gall coloration, and since the link between cytokinins and pigmentation is not obligatory, this is an unlikely general explanation of gall pigmentation. The galling habit has evolved independently among numerous insect lineages and habitats, and therefore, the role of gall pigmentation may vary. It is the time to test the different hypotheses in the field.