Glutamate 85 and glutamate 228 contribute to the pH-response of the soluble form of chloride intracellular channel 1

The chloride intracellular channel protein, CLIC1, is synthesised as a soluble monomer that can reversibly bind membranes. Soluble CLIC1 is proposed to respond to the low pH found at a membrane surface by partially unfolding and restructuring into a membrane-competent conformation. This transition is proposed to be controlled by strategically located “pH-sensor” residues that become protonated at acidic pH. In this study, we investigate the role of two conserved glutamate residues, Glu85 in the N-domain and Glu228 in the C-domain, as pH-sensors. E85L and E228L CLIC1 variants were created to reduce pH sensitivity by permanently breaking the bonds these residues form. The structure and stability of each variant was compared to the wild type at both pH 7.0 and pH 5.5. Neither substitution significantly altered the structure but both decreased the conformational stability. Furthermore, E85L CLIC1 formed a urea-induced unfolding intermediate state at both pH 7 and pH 5.5 compared to wild-type and E228L CLIC1 which only formed the intermediate at pH 5.5. We conclude that Glu85 and Glu228 are two of the five pH-sensor residues of CLIC1 and contribute to the pH-response in different ways. Glu228 lowers the stability of the native state at pH 5.5, while Glu85 contributes both to the stability of the native state and to the formation of the intermediate state. By putting these interactions into the context of the three previously described CLIC1 pH-sensor residues, we propose a mechanism for the conversion of CLIC1 from the soluble state to the pre-membrane form.     

Rapid Antiretroviral Therapy Initiation for Women in an HIV-1 Prevention Clinical Trial Experiencing Primary HIV-1 Infection during Pregnancy or Breastfeeding

During an HIV-1 prevention clinical trial in East Africa, we observed 16 cases of primary HIV-1 infection in women coincident with pregnancy or breastfeeding. Nine of eleven pregnant women initiated rapid combination antiretroviral therapy (ART), despite having CD4 counts exceeding national criteria for ART initiation; breastfeeding women initiated ART or replacement feeding. Rapid ART initiation during primary HIV-1 infection during pregnancy and breastfeeding is feasible in this setting.     

Cardiolipin biosynthesis and remodeling enzymes are altered during development of heart failure

Cardiolipin (CL) is responsible for modulation of activities of various enzymes involved in oxidative phosphorylation. Although energy production decreases in heart failure (HF), regulation of cardiolipin during HF development is unknown. Enzymes involved in cardiac cardiolipin synthesis and remodeling were studied in spontaneously hypertensive HF (SHHF) rats, explanted hearts from human HF patients, and nonfailing Sprague Dawley (SD) rats. The biosynthetic enzymes cytidinediphosphatediacylglycerol synthetase (CDS), phosphatidylglycerolphosphate synthase (PGPS) and cardiolipin synthase (CLS) were investigated. Mitochondrial CDS activity and CDS-1 mRNA increased in HF whereas CDS-2 mRNA in SHHF and humans, not in SD rats, decreased. PGPS activity, but not mRNA, increased in SHHF. CLS activity and mRNA decreased in SHHF, but mRNA was not significantly altered in humans. Cardiolipin remodeling enzymes, monolysocardiolipin acyltransferase (MLCL AT) and tafazzin, showed variable changes during HF. MLCL AT activity increased in SHHF. Tafazzin mRNA decreased in SHHF and human HF, but not in SD rats. The gene expression of acyl-CoA: lysocardiolipin acyltransferase-1, an endoplasmic reticulum MLCL AT, remained unaltered in SHHF rats. The results provide mechanisms whereby both cardiolipin biosynthesis and remodeling are altered during HF. Increases in CDS-1, PGPS, and MLCL AT suggest compensatory mechanisms during the development of HF. Human and SD data imply that similar trends may occur in human HF, but not during nonpathological aging, consistent with previous cardiolipin studies.     

Management of Enuresis

In 144 enuretic children at four Southwark school health service clinics a good measure of success was achieved by sympathetic handling alone. Most of the remaining patients responded to a buzzer; nevertheless, its use needs to be carefully presented and supervised. The use of drugs is questioned.     

New Intercommunity Infanticides by the Chimpanzees of Ngogo,Kibale National Park,Uganda

Hostile intercommunity relations, including attacking and killing extra-community infants of both sexes have occurred at most wild chimpanzee sites. We describe three recent cases of intercommunity attacks on infants committed by members of the Ngogo chimpanzee community in Kibale National Park, Uganda. Two of the attacks resulted in confirmed infanticides while a third attack probably resulted in the infant's death. In common with previous accounts of chimpanzee infanticides, the attacks described here occurred during boundary patrols outside the Ngogo community's usual range, adult and adolescent males were the main participants, one infant was cannibalized after being killed, and the victims’ mothers did not accompany the attacking party back to the Ngogo range. However, the patrol parties during each infanticide were larger than before and included females from the Ngogo community. Our observations indirectly support both the range expansion and imbalance of power hypotheses, which address why and under which conditions chimpanzee intercommunity encounters lead to aggression. These cases of intercommunity infanticide add to the growing database of the phenomenon in wild chimpanzees.     

THE EFFECTIVENESS OF THE SPECTRUM IN CHLOROPHYLL FORMATION

1. Although the carotenoid pigments are present in large concentration in the plastids of etiolated Avena seedlings as compared with protochlorophyll, the pigment precursor of chlorophyll, it is possible to show that the carotenoids do not act as filters of the light incident on the plant in the blue region of the spectrum where they absorb heavily. This suggests that the carotenoids are located behind the protochlorophyll molecules in the plastids. 2. Since the carotenoids do not screen and light is necessary for chlorophyll formation, an effectiveness spectrum of protochlorophyll can be obtained which is the reciprocal of the light energy necessary to produce a constant amount of chlorophyll with different wavelengths. The relative effectiveness of sixteen spectral regions in forming chlorophyll was determined. 3. From the effectiveness spectrum, one can conclude that protochlorophyll is a blue-green pigment with major peaks of absorption at 445 mµ, and 645 mµ, and with smaller peaks at 575 and 545 mµ. The blue peak is sharp, narrow, and high, the red peak being broader and shorter. This differs from previous findings where the use of rougher methods indicated that red light was more effective than blue and did not give the position of the peaks of absorption or their relative heights. 4. The protochlorophyll curve is similar to but not identical with chlorophyll. The ratio of the peaks of absorption in the blue as compared to the red is very similar to chlorophyll a, but the position of the peaks resembles chlorophyll b. 5. There is an excellent correspondence between the absorption properties of this "active" protochlorophyll and what is known of the absorption of a chemically known pigment studied in impure extracts of seed coats of the Cucurbitaceae. Conclusive proof of the identity of the two substances awaits chemical purification, but the evidence here favors the view that the pumpkin seed substance, which is chemically chlorophyll a minus two hydrogens, is identical with the precursor of chlorophyll formation found in etiolated plants.     

Effects of amino acids and derivatives of cyclic adenosine 3′, 5′-monophosphate on the production of three exoenzymes by Staphylococcus, simulans biovar staphylolyticus

The extracellular protease, endopeptidase, and hexosaminidase produced by $\text{Staphylococcus}\text{,}\text{simulans}\text{biovar}\text{staphylolyticus}$ were neither induced nor repressed by amino acids but required a tryptic digest of casein for their production. Catabolite repression of exoenzyme production by glucose was not affected by exogenous cyclic adenosine 3′, 5′-monophosphate but was partially relieved by di- or monobutyryl derivatives of this compound.     

Seasonality in the altitude–diversity pattern of Alpine moths

Altitudinal gradients are frequently used to study environmental effects on species diversity. Recent quantitative studies on Lepidoptera focussed on tropical mountain systems and often reported unimodal diversity peaks at “mid-elevations”;, a pattern also often found in other taxa. Here we used methodologically comparable, nocturnal Macrolepidoptera samples from the Swiss Alps to analyze environmental correlates of diversity. Using seasonal data (monthly samples from April to November at altitudes between 600 and 2400 m a.s.l.) allowed to decouple altitude and some climate variables for analyses. We found that the altitude–diversity pattern changes with season. In spring and autumn, diversity decreased with increasing altitude, while we found a unimodal peak of diversity at mid-elevations during summer. This excluded all hypothetical causes of diversity variation that do not allow for seasonality. Temperature was an important correlate of diversity, whereas precipitation was not. These results were separately corroborated for the two most common families (Noctuidae and Geometridae). However, diversity patterns of the two families were not particularly close, and unexplained variance of climatic explanations was substantial in all cases. The patterns of faunal overlap did not explain the unimodal diversity pattern, and we claim that we lack a generally valid explanation for this common phenomenon.