Functional analysis of the gene cluster involved in production of the bacteriocin circularin A by Clostridium beijerinckii ATCC 25752

A region of 12 kb flanking the structural gene of the cyclic antibacterial peptide circularin A of Clostridium beijerinckii ATCC 25752 was sequenced, and the putative proteins involved in the production and secretion of circularin A were identified. The genes are tightly organized in overlapping open reading frames. Heterologous expression of circularin A in Enterococcus faecalis was achieved, and five genes were identified as minimally required for bacteriocin production and secretion. Two of the putative proteins, CirB and CirC, are predicted to contain membrane-spanning domains, while CirD contains a highly conserved ATP-binding domain. Together with CirB and CirC, this ATP-binding protein is involved in the production of circularin A. The fifth gene, cirE, confers immunity towards circularin A when expressed in either Lactococcus lactis or E. faecalis and is needed in order to allow the bacteria to produce bacteriocin. Additional resistance against circularin A is conferred by the activity of the putative transporter consisting of CirB and CirD.     

Apathy syndrome: a clinical entity?

Apathy is defined as a disorder of motivation that expresses itself at an emotional, cognitive and behavioural level. Apathy can occur as a symptom and a syndrome. In the recent years diagnostic criteria and a number of scales for measuring apathy in elderly with psychiatric or neurological disorders have been introduced. Two scales are specifically developed to measure apathy, the Apathy Evaluation Scale (AES) from Marin and the Apathy Scale (AS) from Starkstein. Both scales have been translated into Dutch. The AS is more convenient. The AS in addition can be used when applying the criteria for the apathy syndrome which has been introduced in 2001 by Starkstein. In addition, the Neuropsychiatric Inventory (NPI) and the 'Gedragsobservatieschaal voor de Intramurale Psychogeniatrie' (GIP) (a scale in Dutch) have an apathy domain. Conceptual problems surrounding apathy have only partly been resolved. The criteria for the apathy syndrome can only be used for assessing the extent of the problem. Apathy and depression are strongly correlated. Studies show that apathy as a syndrome can occur without concomitant depression in the elderly, but regularly occurs besides a depressive disorder, in percentages varying between 9% and 53% of the population under study. Especially the varying validity of an apathy syndrome in relation to late life depression needs further clarification.     

Deficiency in the organic cation transporters 1 and 2 (Oct1/Oct2 [Slc22a1/Slc22a2]) in mice abolishes renal secretion of organic cations

The polyspecific organic cation transporters 1 and 2 (Oct1 and -2) transport a broad range of substrates, including drugs, toxins, and endogenous compounds. Their strategic localization in the basolateral membrane of epithelial cells in the liver, intestine (Oct1), and kidney (Oct1 and Oct2) suggests that they play an essential role in removing noxious compounds from the body. We previously showed that in Oct1(-/-) mice, the hepatic uptake and intestinal excretion of organic cations are greatly reduced. Since Oct1 and Oct2 have extensively overlapping substrate specificities, they might be functionally redundant. To investigate the pharmacologic and physiologic roles of these proteins, we generated Oct2 single-knockout and Oct1/2 double-knockout mice. Oct2(-/-) and Oct1/2(-/-) mice are viable and fertile and display no obvious phenotypic abnormalities. Absence of Oct2 in itself had little effect on the pharmacokinetics of tetraethylammonium (TEA), but in Oct1/2(-/-) mice, renal secretion of this compound was completely abolished, leaving only glomerular filtration as a TEA clearance mechanism. As a consequence, levels of TEA were substantially increased in the plasma of Oct1/2(-/-) mice. This study shows that Oct1 and Oct2 together are essential for renal secretion of (small) organic cations. A deficiency in these proteins may thus result in increased drug sensitivity and toxicity.     

Apolipoprotein E4 and memory decline in the elderly

The objective of this study was to investigate whether the association between Apolipoprotein E4 (ApoE4) and memory decline is modified by baseline general cognitive impairment and age in a population-based elderly sample. Subjects were participants in the Longitudinal Aging Study Amsterdam (LASA). The study sample consisted of 1,243 subjects, 62-85 years old, with a Mini-Mental State Examination (MMSE) score between 21-30 and known ApoE phenotypes. Memory performance was measured with a short version of the Auditory Verbal Learning Test (AVLT) at baseline and repeated after three years (N = 854). Memory decline was defined as a decrease of at least one standard deviation from the mean change score on immediate recall, delayed recall and retention. ApoE4 was associated with memory decline in cognitively impaired subjects (MMSE 21-26), but not in cognitively normal subjects (MMSE 27-30). In particular cognitively impaired E4 carriers older than 75 years were at high risk of memory decline. Contrary to AD studies, our study suggests that the risk of ApoE4 on memory decline does not decrease with ageing.     

Myocyte enlargement, differentiation, and proliferation kinetics in the fetal sheep heart.

The generation of new myocytes is an essential process of in utero heart growth. Most, or all, cardiac myocytes lose their capacity for proliferation during the perinatal period through the process of terminal differentiation. An increasing number of studies focus on how experimental interventions affect cardiac myocyte growth in the fetal sheep. Nevertheless, fundamental questions about normal growth of the fetal heart remain unanswered. In this study, we determined that during the last third of gestation the hearts of fetal sheep grew primarily by four processes. 1) Myocyte proliferation contributed substantially to daily cardiac mass gain, and the number of cardiac myocytes continued to increase to term. 2) The (hitherto unrecognized) contribution to cardiac growth by the increase in myocyte size associated with the transition from mononucleation to binucleation (terminal differentiation) became considerable from approximately 115 days of gestational age (dGA) until term (145dGA). Because binucleation became the more frequent outcome of myocyte cell cycle activity after approximately 115dGA, the number of binucleated myocytes increased at the expense of the number of mononucleated myocytes. Both the interval between nuclear divisions and the duration of cell cycle activity in myocytes decreased substantially during this same period. Finally, cardiac growth was in part due to enlargement of 3) mononucleated and 4) binucleated myocytes, which grew in cross-sectional diameter but not length during the last third of gestation. These data on normal cardiac growth may enable a more detailed understanding of the consequences of experimental and pathological interventions in prenatal life.     

Maturation of the angiotensin II cardiovascular response in the embryonic White Leghorn chicken (Gallus gallus)

Angiotensin II (Ang II) is an important regulator of cardiovascular function in adult vertebrates. Although its role in regulating the adult system has been extensively investigated, the cardiovascular response to Ang II in embryonic vertebrates is relatively unknown. We investigated the potential of Ang II as a regulator of cardiovascular function in embryonic chickens, which lack central nervous system control of cardiovascular function throughout the majority of incubation. The cardiovascular response to Ang II in embryonic chickens was investigated over the final 50% of their development. Ang II produced a dose-dependent increase in arterial pressure on each day of development studied, and the response increased in intensity as development progressed. The Ang II type-1 receptor nonspecific competitive peptide antagonist [Sar¹ ile⁸] Ang II blocked the cardiovascular response to subsequent injections of Ang II on day 21 only. The embryonic pressure response to Ang II (hypertension only) differed from that of adult chickens, in which initial hypotension is followed by hypertension. The constant level of gene expression for the Ang II receptor, in conjunction with an increasing pressure response to the peptide, suggests that two Ang II receptor subtypes are present during chicken development. Collectively, the data indicate that Ang II plays an important role in the cardiovascular development of chickens; however, its role in maintaining basal function requires further study.     

Mild cognitive impairment: a prodromal phase of dementia?

Cognitive decline without dementia is common among older persons. A variety of clinical concepts have been introduced in the past 30 years, in order to describe these cognitive deficits arising in older persons. The most frequently used concept is Mild Cognitive Impairment (MCI). MCI is generally seen as a prodromal phase of Alzheimer disease (AD). Several concepts are described, with the neuropsychiatric features and predictors of conversion to dementia c.q. AD. Finally, consequences of preclinically diagnoses for health care are clarified.     

Genetic portrait of Lisboa immigrant population from Cabo Verde with mitochondrial DNA analysis

Journal of Genetics -