Frontal bone fragment of<Emphasis Type="Italic">Homo erectus</Emphasis> from Sangiran,Java

In 1994 a hominid frontal bone fragment was found in the river floor of the Brangkal River, the Sangiran area, Central Java. The original stratigraphic level is not known at present stage of the research. But it is possible that the bone was derived from the Grenzbank zone of the Bapang Formation (Lower/Middle Pleistocene). Morphological features of the bone, such as a thick and continuous supraorbital torus, a wide and flat supratoral plane, and a flat and strongly inclined frontal squame suggest that the bone is assigned to JavaneseHomo erectus, especially to the Sangiran and Trinil group of it.     

A Naturally Occurring Mutation in ropB Suppresses SpeB Expression and Reduces M1T1 Group A Streptococcal Systemic Virulence

Epidemiological studies of group A streptococcus (GAS) have noted an inverse relationship between SpeB expression and invasive disease. However, the role of SpeB in the course of infection is still unclear. In this study we utilize a SpeB-negative M1T1 clinical isolate, 5628, with a naturally occurring mutation in the gene encoding the regulator RopB, to elucidate the role of RopB and SpeB in systemic virulence. Allelic exchange mutagenesis was used to replace the mutated ropB allele in 5628 with the intact allele from the well characterized isolate 5448. The inverse allelic exchange was also performed to replace the intact ropB in 5448 with the mutated allele from 5628. An intact ropB was found to be essential for SpeB expression. While the ropB mutation was shown to have no effect on hemolysis of RBC''s, extracellular DNase activity or survival in the presence of neutrophils, strains with the mutated ropB allele were less virulent in murine systemic models of infection. An isogenic SpeB knockout strain containing an intact RopB showed similarly reduced virulence. Microarray analysis found genes of the SpeB operon to be the primary target of RopB regulation. These data show that an intact RopB and efficient SpeB production are necessary for systemic infection with GAS.     

Circadian clock,carcinogenesis, chronochemotherapy connections

The circadian clock controls the expression of nearly 50% of protein coding genes in mice and most likely in humans as well. Therefore, disruption of the circadian clock is presumed to have serious pathological effects including cancer. However, epidemiological studies on individuals with circadian disruption because of night shift or rotating shift work have produced contradictory data not conducive to scientific consensus as to whether circadian disruption increases the incidence of breast, ovarian, prostate, or colorectal cancers. Similarly, genetically engineered mice with clock disruption do not exhibit spontaneous or radiation-induced cancers at higher incidence than wild-type controls. Because many cellular functions including the cell cycle and cell division are, at least in part, controlled by the molecular clock components (CLOCK, BMAL1, CRYs, PERs), it has also been expected that appropriate timing of chemotherapy may increase the efficacy of chemotherapeutic drugs and ameliorate their side effect. However, empirical attempts at chronochemotherapy have not produced beneficial outcomes. Using mice without and with human tumor xenografts, sites of DNA damage and repair following treatment with the anticancer drug cisplatin have been mapped genome-wide at single nucleotide resolution and as a function of circadian time. The data indicate that mechanism-based studies such as these may provide information necessary for devising rational chronochemotherapy regimens.     

Heavy metals (Cd, Pb, Zn, Ni, Cu and Cr(III)) removal from water in Malaysia: post treatment by high quality limestone

This paper presents the results of research on heavy metals removal from water by filtration using low cost coarse media which could be used as an alternative approach to remove heavy metals from water or selected wastewater. A series of batch studies were conducted using different particle media (particle size 2.36-4.75 mm) shaken with different heavy metal solutions at various pH values to see the removal behaviour for each metal. Each solution of cadmium (Cd), lead (Pb), zinc (Zn), nickel (Ni), copper (Cu) and chromium (Cr(III)) with a concentration of 2 mg/L was shaken with the media. At a final pH of 8.5, limestone has significantly removed more than 90% of most metals followed by 80% and 65% removals using crushed bricks and gravel, respectively. The removal by aeration and settlement methods without solid media was less than 30%. Results indicated that the removal of heavy metals was influenced by the media and not directly by the pH. Investigations on the removal behaviour of these metals indicated that rough solid media with the presence of carbonate were beneficial for the removal process. Adsorption and precipitation as metals oxide and probably as metals carbonate were among the two mechanisms that contributed to the removal of metals from solution.     

Terpene biosynthesis in glandular trichomes of hop

Hop (Humulus lupulus L. Cannabaceae) is an economically important crop for the brewing industry, where it is used to impart flavor and aroma to beer, and has also drawn attention in recent years due to its potential pharmaceutical applications. Essential oils (mono- and sesquiterpenes), bitter acids (prenylated polyketides), and prenylflavonoids are the primary phytochemical components that account for these traits, and all accumulate at high concentrations in glandular trichomes of hop cones. To understand the molecular basis for terpene accumulation in hop trichomes, a trichome cDNA library was constructed and 9,816 cleansed expressed sequence tag (EST) sequences were obtained from random sequencing of 16,152 cDNA clones. The ESTs were assembled into 3,619 unigenes (1,101 contigs and 2,518 singletons). Putative functions were assigned to the unigenes based on their homology to annotated sequences in the GenBank database. Two mono- and two sesquiterpene synthases identified from the EST collection were expressed in Escherichia coli. Hop MONOTERPENE SYNTHASE2 formed the linear monterpene myrcene from geranyl pyrophosphate, whereas hop SESQUITERPENE SYNTHASE1 (HlSTS1) formed both caryophyllene and humulene from farnesyl pyrophosphate. Together, these enzymes account for the production of the major terpene constituents of the hop trichomes. HlSTS2 formed the minor sesquiterpene constituent germacrene A, which was converted to β-elemene on chromatography at elevated temperature. We discuss potential functions for other genes expressed at high levels in developing hop trichomes.     

Cranial morphology of Javanese Homo erectus: new evidence for continuous evolution, specialization, and terminal extinction

Our current knowledge of the evolution of Homo during the early to middle Pleistocene is far from complete. This is not only because of the small number of fossil samples available, but also due to the scarcity of standardized datasets which are reliable in terms of landmark identification, interobserver error, and other distorting factors. This study aims to accurately describe the cranial morphological changes of H. erectus in Java using a standardized set of measurements taken by the authors from 18 adult crania from Sangiran, Trinil, Sambungmacan, and Ngandong. The identification of some obscure landmarks was aided by the use of micro-CT imaging. While recent studies tend to emphasize evolutionary conservatism in Javanese H. erectus, our results reinforce the theory that chronologically later groups experienced distinct morphological changes in a number of cranial traits. Some of these changes, particularly those related to brain size expansion, are similar to those observed for the genus Homo as a whole, whereas others are apparently unique specializations restricted to Javanese H. erectus. Such morphological specializations in Java include previously undescribed anteroposterior lengthening of the midcranial base and an anterior shift of the posterior temporal muscle, which might have influenced the morphology of the angular torus and supramastoid sulcus. Analyses of morphological variation indicate that the three crania from Sambungmacan variously fill the morphological gap between the chronologically earlier (Bapang-AG, Bapang Formation above the Grenzbank zone in Sangiran) and later (Ngandong) morphotypes of Java. At least one of the Bapang-AG crania, Sangiran 17, also exhibits a few characteristics which potentially indicate evolution toward the Ngandong condition. These strongly suggest the continuous, gradual morphological evolution of Javanese H. erectus from the Bapang-AG to Ngandong periods. The development of some unique features in later Javanese H. erectus supports the hypothesis that this Javanese lineage went extinct without making significant contributions to the ancestry of modern humans.     

HIV-1 Env vaccine comprised of electroporated DNA and protein co-administered with Talabostat

Selection of potent yet low reactogenic adjuvants for protein immunization is important for HIV-1 vaccine development. Immunogenicity of electroporated DNA (HIV env) and recombinant gp120, administered with either QS-21 or the orally administered immunomodulator, Talabostat, was evaluated in BALB/c mice. Electroporation of low dose DNA elicited Th1 cytokines and anti-envelope antibodies. Immunization with gp120 protein alone with or without Talabostat elicited lower Th1 and Th2 cytokine levels but comparable anti-gp120 antibodies to QS-21-formulated protein. Boosting of DNA-primed mice with gp120/Talabostat induced similar anti-gp120 antibody titers and slightly higher levels of Th1 and Th2 cytokines relative to QS-21-formulated protein. Induction of CD8⁺ and CD4⁺ T cells and functional CTL activity was noted. These results highlight the potential use of orally administered Talabostat for efficient protein boosting of antibody and T-cell responses primed by DNA.     

A homozygous mutation in human PRICKLE1 causes an autosomal-recessive progressive myoclonus epilepsy-ataxia syndrome

Progressive myoclonus epilepsy (PME) is a syndrome characterized by myoclonic seizures (lightning-like jerks), generalized convulsive seizures, and varying degrees of neurological decline, especially ataxia and dementia. Previously, we characterized three pedigrees of individuals with PME and ataxia, where either clinical features or linkage mapping excluded known PME loci. This report identifies a mutation in PRICKLE1 (also known as RILP for REST/NRSF interacting LIM domain protein) in all three of these pedigrees. The identified PRICKLE1 mutation blocks the PRICKLE1 and REST interaction in vitro and disrupts the normal function of PRICKLE1 in an in vivo zebrafish overexpression system. PRICKLE1 is expressed in brain regions implicated in epilepsy and ataxia in mice and humans, and, to our knowledge, is the first molecule in the noncanonical WNT signaling pathway to be directly implicated in human epilepsy.     

Cardiac Myosin-binding protein C modulates the tuning of the molecular motor in the heart

Cardiac myosin binding protein C (cMyBP-C) is an important regulator of cardiac contractility. Its precise effect on myosin cross-bridges (CBs) remains unclear. Using a cMyBP-C^−/− mouse model, we determined how cMyBP-C modulates the cyclic interaction of CBs with actin. From papillary muscle mechanics, CB characteristics were provided using A. F. Huxley's equations. The probability of myosin being weakly bound to actin was higher in cMyBP-C^−/− than in cMyBP-C^+/+. However, the number of CBs in strongly bound, high-force generated state and the force generated per CB were lower in cMyBP-C^−/−. Overall CB cycling and the velocity of CB tilting were accelerated in cMyBP-C^−/−. Taking advantage of the presence of cMyBP-C in cMyBP-C^+/+ myosin solution but not in cMyBP-C^−/−, we also analyzed the effects of cMyBP-C on the myosin-based sliding velocity of actin filaments. At baseline, sliding velocity and the relative isometric CB force, as determined by the amount of α-actinin required to arrest thin filament motility, were lower in cMyBP-C^−/− than in cMyBP-C^+/+. cAMP-dependent protein kinase-mediated cMyBP-C phosphorylation further increased the force produced by CBs. We conclude that cMyBP-C prevents inefficient, weak binding of the myosin CB to actin and has a critical effect on the power-stroke step of the myosin molecular motor.