The Pif1p subfamily of helicases: region-specific DNA helicases?

DNA helicases are required for DNA replication, recombination and repair. Despite a common enzymatic function - the ability to unwind duplex DNA - most helicases share only limited amino acid sequence similarity. Helicases that have significant sequence similarity define a subfamily. It remains unclear, however, how this sequence similarity relates to helicase function. The Saccharomyces cerevisiae Pif1p helicase is the prototype member of a helicase subfamily that is conserved from yeasts to humans. As the two Pif1p subfamily members studied to date affect the same DNA sequences, the amino acid similarity that defines this subfamily might reflect common substrates.     

Trypanosomes and mammalian sperm: one of a kind?

Flagellar-mediated motility is an indispensable function for cell types as evolutionarily distant as mammalian sperm and kinetoplastid parasites, a large group of flagellated protozoa that includes several important human pathogens. Despite the obvious importance of flagellar motility, little is known about the signalling processes that direct the frequency and wave shape of the flagellar beat, or those that provide the motile cell with the necessary environmental cues that enable it to aim its movement. Similarly, the energetics of the flagellar beat and the problem of a sufficient ATP supply along the entire length of the beating flagellum remain to be explored. Recent proteome projects studying the flagella of mammalian sperm and kinetoplastid parasites have provided important information and have indicated a surprising degree of similarities between the flagella of these two cell types.     

Bacterial lipoxygenases, a new subfamily of enzymes? A phylogenetic approach

Lipoxygenases (EC. 1.13.11.12) are a non-heme iron enzymes consisting of one polypeptide chain folded into two domains, the N-terminal domain and the catalytic moiety β-barrel domain. They catalyze the dioxygenation of 1Z,4Z-pentadiene moieties of polyunsaturated fatty acids obtaining hydroperoxy fatty acids. For years, the presence of lipoxygenases was considered a eukaryotic feature, present in mammals, plants, small marine invertebrates, and fungi, but now, some lipoxygenase sequences have been detected on prokaryotic organisms, changing the idea that lipoxygenases are exclusively a eukaryotic affair. Lipoxygenases are involved in different types of reactions on eukaryote organisms where the biological role and the structural characteristics of these enzymes are well studied. However, these aspects of the bacterial lipoxygenases have not yet been elucidated and are unknown. This revision discusses biochemical aspects, biological applications, and some characteristics of these enzymes and tries to determine the existence of a subfamily of bacterial lipoxygenases in the context of the phylogeny of prokaryotic lipoxygenases, supporting the results of phylogenetic analyzes with the comparison and discussion of structural information of the first prokaryotic lipoxygenase crystallized and other eukaryotic lipoxygenases structures.     

DNA accessibility: a determinant of mammalian cell differentiation?

Rats bearing intracerebral 9L tumors were whole-brain irradiated with 1250 to 5000 rad, and the in situ DNA repair kinetics of the undifferentiated tumor cells and terminally differentiated cerebellar neurons were examined by alkaline sucrose gradient sedimentation in zonal rotors with gradient reorienting capability. Biphasic repair kinetics were observed for both tumor cells and cerebellar neurons. Quantitation and analysis of the slow phase of the repair process suggest that the dividing tumor cell genome is completely accessible to the enzymatic repair machinery, while it is possible that the genome of the permanently nondividing neuron may contain a region that is inaccessible to this repair machinery.     

Zapaliinae,a new subfamily of Tithonian–Berriasian ataxioceratid ammonites

The recent recognition of the earliest Andean Tithonian ammonite fauna (Picunleufuense Zone) has allowed a balanced classification of the ataxioceratid ammonites, reflecting their phylogenetic relationships. The Picunleufuense Zone fauna, first recognized in the Neuquén Basin at the base of the Vaca Muerta Formation, is represented by numerous records of sparse ammonite faunas from Antarctica, the Austral Basin and the Tarapacá Basin (N. Chile and S. Peru). These Southeastern Pacific faunas include the Tithonian genera Indansites, Choicensisphinctes, Zapalia, Krantziceras (Tithonian–lower Berriasian) and Platydiscus. These five genera are grouped in a new subfamily established in this paper: Zapaliinae subfam. nov. (type genus: Zapalia). The origin of Indansites and Choicensisphinctes (possibly via Indanistes) from Lithacoceras is discussed. Zapalia must have been originated from Indanistes in the upper Proximus Zone. Platydiscus could have been originated from Krantziceras. The Tithonian Southeastern Pacific ataxioceratids (Zapaliinae subfam. nov.) form a group well separated from the Tithonian Indo-Madagascan Virgatosphinctinae.     

Acanthochlamydoideae—A new subfamily of Amaryllidaceae

Acanthochlamydoideae, a new subfamily of Amaryllidaceae, is proposed in the present paper, based upon the monotypic genus Acanthochlamys which was detected bythe writer in 1979 and named Didymocolpus as a new genus but was preceded by P. C.Kao in 1980 under the former name. The genus is indeed of great morphological interest. It has semicylindric leaves with a deep furrow on the ventral and dorsal sidesrespectively. The lower part of the leaf is connate with, or adnate to, the lower midrib of a rather large and membranous vagina . Such a feature, as far as we know, isvery rare in the monocotyledons. The flower resembles that of Amaryllidaceae in having inferior ovary, six stamensand corolla-like perianth with a rather long tube. But it is quite different in othercharacters, such as head-like cyme, leaf-like bracts and bisulcate leaves, which all areforeign to any taxon known in the Amaryllidaceae. On the other hand, it bears someresemblance particularly in habit and inflorescence to Campynemanthe of the Hypoxidaceae, and also to Borya and Bartlingia of the Liliaceae (in the tribe Johnsonieae), but differs in its long perianth-tube and curious leaf structure. It is highlyprobable that the resemblance between them is only superficial and not indicative ofdirect or close relationship. This is no doubt a very curious plant of which we still know incompletely, andfor which an appropriate place in the monocotyledons has not yet been found. Considering its floral characters, however, it seems safe for the present to place it as aseparate subfamily in the Amaryllidaceae and is juxtaposed with the Ixiolirioideaeand Amaryllidoideae, the only two subfamilies of Amaryllidaceae according to H. Melchior (1964), and, of course, to either of them it is not directly related. Its true affinityremains problematic. The only species, Acanthochlamys bracteata, is found in Mar-er-kan (102°12'N,31°47'E), Qian-ning (101°30'N, 30°33'E), Xiang-cheng (99°39'N, 28°54'E) and Daucheng (100°10'N, 29°03'E) in western Sichuan of southwest China, in open bushlandor grassland at an altitude between 2700—3500 meters. Its geographical distribution ismapped and its morphological details are illustrated to facilitate its identification.     

Chemokines: a new class of neuromodulator?

Chemokines are not only found in the immune system or expressed in inflammatory conditions: they are constitutively present in the brain in both glial cells and neurons. Recently, the possibility has been raised that they might act as neurotransmitters or neuromodulators. Although the evidence is incomplete, emerging data show that chemokines have several of the characteristics that define neurotransmitters. Moreover, their physiological actions resemble those of neuromodulators in the sense that chemokines usually have few effects by themselves in basal conditions, but modify the induced release of neurotransmitters or neuropeptides. These findings, together with the pharmacological development of agonists and antagonists that are selective for chemokine receptors and can cross the blood-brain barrier, open a new era of research in neuroscience.     

The genus Vietbocap Lourenço & Pham, 2010 (Scorpiones: Pseudochactidae); proposition of a new subfamily and description of a new species from Laos

A new species of scorpion belonging to the family Pseudochactidae and the genus Vietbocap is described from the Tham Nam Lot cave, located in the Laotian part of the Khammouan-Ke Bang karst in Southeast Asia. Like the previously described species of the genus, Vietbocap lao sp. n. is a true troglobiont, but presents an even greater degree of adaptation to cave life, with a total lack of pigmentation and a very weak sclerotization of the tegument. This is the third troglobitic element known for the family Pseudochactidae. It represents the fifth known species of pseudochactid, four of which are from the Khammouan-Ke Bang karst system. Taking into account some marked differences between Vietbocap and the other two pseudochactid genera, a new subfamily, Vietbocapinae subfam. n., is proposed to accommodate this genus.     

Allosteric control of mammalian DNA methyltransferases – a new regulatory paradigm

In mammals, DNA methylation is introduced by the DNMT1, DNMT3A and DNMT3B methyltransferases, which are all large multi-domain proteins containing a catalytic C-terminal domain and an N-terminal part with regulatory functions. Recently, two novel regulatory principles of DNMTs were uncovered. It was shown that their catalytic activity is under allosteric control of N-terminal domains with autoinhibitory function, the RFT and CXXC domains in DNMT1 and the ADD domain in DNMT3. Moreover, targeting and activity of DNMTs were found to be regulated in a concerted manner by interactors and posttranslational modifications (PTMs). In this review, we describe the structures and domain composition of the DNMT1 and DNMT3 enzymes, their DNA binding, catalytic mechanism, multimerization and the processes controlling their stability in cells with a focus on their regulation and chromatin targeting by PTMs, interactors and chromatin modifications. We propose that the allosteric regulation of DNMTs by autoinhibitory domains acts as a general switch for the modulation of the function of DNMTs, providing numerous possibilities for interacting proteins, nucleic acids or PTMs to regulate DNMT activity and targeting. The combined regulation of DNMT targeting and catalytic activity contributes to the precise spatiotemporal control of DNMT function and genome methylation in cells.     

Convergence and parallelism: is a new life ahead of old concepts?

In comparative biology, character observations initially separate similar and dissimilar characters. Only similar characters are considered for phylogeny reconstruction; their homology is attested in a two‐step process, firstly a priori of phylogeny reconstruction by accurate similarity statements, and secondly a posteriori of phylogeny analysis by congruence with other characters. Any pattern of non‐homology is then a homoplasy, commonly, but vaguely, associated with “convergence”. In this logical scheme, there is no way to analyze characters which look similar, but cannot meet usual criteria for homology statements, i.e., false similarity detected a priori of phylogenetic analysis, even though such characters may represent evolutionarily significant patterns of character transformations. Because phylogenies are not only patterns of taxa relationships but also references for evolutionary studies, we propose to redefine the traditional concepts of parallelism and convergence to associate patterns of non‐homology with explicit theoretical contexts: homoplasy is restricted to non‐similarity detected a posteriori of phylogeny analysis and related to parallelism; non‐similarity detected a priori of phylogenetic analysis and necessarily described by different characters would then correspond to a convergence event s. str. We propose to characterize these characters as heterologous (heterology). Heterology and homoplasy correspond to different non‐similarity patterns and processes; they are also associated with different patterns of taxa relationships: homoplasy can occur only in non‐sister group taxa; no such limit exists for heterology. The usefulness of these terms and concepts is illustrated with patterns of acoustic evolution in ensiferan insects. © The Willi Hennig Society 2005.     

Anticoagulation and sepsis: the opportunity for a new use of heparin?

Sepsis is a leading cause of morbidity and mortality worldwide, and the magnitude of the problem seems higher in developing countries. In the last two decades the accepted standard treatment has resulted in only a slight decrease in mortality, and that decrease has been overshadowed by an almost 300% increase in incidence. Recently has been documented the close relationship between infection, inflammation and coagulation in sepsis has been documented; and although clinically overt disseminated intravascular coagulation may occur in only 30% to 50% of septic patients, the activation of the coagulation cascade is an early and common response to the infectious challenge. Moreover most of the molecules involved in the pro-coagulant state that characterizes sepsis are also powerful generators or amplifiers of the inflammatory response. These findings have fostered a comprehensive body of research regarding biological products with anticoagulant activity, as additional therapies for patients with the most severe states of the sepsis syndrome. This review explains the biological and molecular aspects that support the potential use of anticoagulant treatments in sepsis. Furthermore, we analyze the evidence provided by experimental and pre-clinical studies, which suggest the usefulness of heparin as an effective complementary treatment throughout the clinical stages of the disease.     

Health psychology: a new form of psychotherapy?

Psychotherapy in its traditional form is being challenged due to managed care pressures. Psychotherapy using the model of health psychology can adapt well in a managed care environment. Differences between traditional psychotherapy and the psychotherapeutic approach of health psychology are discussed in this article, with a focus on an overview of health psychology and its applications to primary care, and the concept of single-session therapy. A case example of a sample treatment emphasizing the model of brief health psychology treatment is illustrated.     

TCL1: a new drug target in lymphoid and germ-cell malignancies?

The protein product of the T-cell leukemia/lymphoma 1 (TCL1) oncogene was recently identified as a novel Akt kinase activator. Its crystal structure predicts regions most likely involved in protein–protein interactions, and complex formation is required for TCL1 to activate Akt. TCL1 is expressed in a broad range of normal and malignant lymphoid cell types and in a high proportion of testicular seminomas of germ cell origin, indicating its potential to serve as a novel anti-cancer drug target. This review is focused on the current state of knowledge of TCL1 and the medical implications of its discovery.     

Is canavanine a natural component of mammalian metabolism?

A group of non-protein amino acids of higher plants, namely l-canavanine, l-canaline, 0-ureido-l-homoserine, and l-canavaninosuccinic acid, have been implicated in mammalian intermediary metabolism. The clinical observations and biochemical basis for this hypothesis as well as conflicting experimental evidence are presented. A possible explanation for the apparent role of these non-protein amino acids in mammalian metabolism is offered.     

Triphalangeal thumb and psychomotor retardation: a new association?

The triphalangeal thumb (TPT) is a rare malformation in which the thumb is presented as a long digit of three phalanges. We describe two brothers showing TPT and psychomotor retardation, especially in language. Difficulties in language development were also observed in children with TPT in another study. The coexistence of TPT and psychomotor retardation in those patients and in the two patients described here suggests that TPT and psychomotor retardation could be part of a syndromic association not described previously.