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An electromyographic study of the pectoralis major in atelines and Hylobates, with special reference to the evolution of a pars clavicularis.

Among primates there is striking variation in the extent of the origin of pectoralis major from the clavicle. A significant clavicular attachment (pars clavicularis) occurs only in Alouatta, Lagothrix, Hylobates, Pan (troglodytes, paniscus and gorilla), and Homo. Interpreting this trait in nonhuman primates as an adaptation to frequent use of a mobile forelimb in climbing and suspension is contraindicated by the absence of a clavicular origin in Ateles and Pongo. We have undertaken a telemetered electromyographic study to determine any special role of the most cranial part of the pectoralis major in comparison to its caudal part, and to the deltoid, during vertical climbing, pronograde quadrupedalism, and armswinging in Ateles, Lagothrix, Alouatta, and Hylobates. The results show that the cranial pectoralis major possesses a role not shared by the caudal fibers: initiation of the recovery phase of the locomotor cycle. When ability to execute rapid or powerful recovery of the adducted forelimb is required in an animal with a shoulder joint lying on a plane cranial to that of the manubrium, the movement will be facilitated if the origin of the pectoralis major is extended onto the clavicle. Such is the case in nonhuman primates possessing this trait. The absence of a clavicular origin in Ateles and Pongo may be related to diminished selective pressures to perfect locomotor modes such as pronograde quadrupedalism, armswinging, or climbing thick vertical trunks, that demand rapid or powerful recovery of the adducted forelimb. If the arboreal ancestor of humans had evolved a clavicular origin of pectoralis major, this animal would be preadapted for certain uses of the forelimb in its bipedal descendant.

Alouatta↗

Spatial and temporal distribution of 7B2 in the pulmonary diffuse neuroendocrine system of the cat.

The postnatal developmental profile of the presence of 7B2 was studied immunocytochemically in the pulmonary diffuse neuroendocrine system of the cat. Labelling was found in neuroepithelial bodies (NEB) but not in solitary neuroendocrine cells. The identity of NEB was confirmed on adjacent serial sections by the immunostaining for protein gene product 9.5, a pan-neuroendocrine marker. The first 3 weeks after birth 7B2 stained NEB were most abundant with a subsequent decline thereafter. The positive correlation between the variation of 7B2 immunoreactivity and number of NEB suggests an important role for 7B2 in NEB.

Animals↗

Role of caspases and apoptosis-inducing factor (AIF) in cladribine-induced apoptosis of B cell chronic lymphocytic leukemia.

We have evaluated the role of caspases and the mitochondrial apoptosis inducing-factor (AIF) in apoptosis induced by cladribine (2CdA), in vitro, in cells from patients of B-CLL and in peripheral blood lymphocytes from normal donors. In sensitive B-CLL cells, apoptosis was characterized by cell shrinking, loss of mitochondrial membrane potential (DeltaPsi(m)), phosphatidylserine exposure, activation of caspases 3, 7, 8 and 9, reduction of Mcl-1 levels, translocation of AIF from mitochondria to nucleus and chromatin condensation. No significant variations in the levels of Bcl-2, Bax and Bak proteins were noticed upon treatment with 2CdA. Co-treatment of cells with the pan-caspase inhibitor Z-VAD-fmk attenuated some morphological and biochemical characteristics of apoptosis and delayed 2CdA-induced DeltaPsi(m) loss, but did not prevent cell death. Z-VAD-fmk did not prevent 2CdA-induced AIF translocation but in this case apoptotic cells displayed only peripheral chromatin condensation, characteristic of AIF action. Reduced or negligible caspase 3 expression did not prevent 2CdA toxicity in cells from four patients. Cells from three patients that responded poorly to 2CdA lacked expression of caspases 9 or 3. Cells from another patient resistant to 2CdA expressed caspases 3, 7, 8 and 9 but they were not activated by treatment. These results indicate that execution of apoptosis is carried out independently by AIF and caspases, which are responsible for the development of apoptotic phenotype in response to 2CdA. Although caspases can also collaborate in DeltaPsi(m) loss, proapoptotic proteins from the Bcl-2 superfamily may be the key inducers of DeltaPsi(m) loss and apoptosis in B-CLL cells sensitive to 2CdA.

Aged↗

Mantle cell lymphoma: a clinicopathological study of 55 cases.

A recently described unifying proposal for mantle cell lymphoma has led to the formulation of strict diagnostic criteria based on morphology, immunology and molecular data to define this specific entity. Previous studies were often based on broader definitions such as centrocytic lymphoma, intermediately differentiated lymphoma or mantle zone lymphoma and, therefore, included a variety of entities with some, but not all, features ascribed to the mantle cell lymphoma. Since the publication of the unifying proposal no comprehensive studies have been published to confirm and support it. We selected 55 cases of mantle cell lymphoma collected in our institution in order to evaluate the validity of the proposal and, by using strict criteria, we analysed the morphological features, their variations and the changes occurring in the course of the disease as well as its clinical behaviour. The analysis of this material demonstrates that mantle cell lymphoma affects predominantly elderly males presenting with an advanced stage of disease. Twenty-four out of 55 patients died with, or of, the disease with a median survival of 32 months, even though most of them received aggressive chemotherapy. In all cases the histological features were strikingly uniform and most cases had a diffuse growth pattern. The neoplastic cells corresponded to small cleaved cells with a minimal variation in shape and size from one case to the other. The phenotype of the neoplastic cells was remarkably constant with expression of several pan-B cell markers, IgM, IgD and CD5, and lack of CD10 and CD23.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Genetic variation of the ompA and 16S rRNA genes of Riemerella anatipestifer.

The genetic diversity of the 16S rRNA and ompA genes of Riemerella anatipestifer was investigated. A 16S rRNA gene-based PCR was able to amplify all 18 Taiwanese strains and 10 reference strains. The identity of 16S rRNA sequence of these strains and seven other sequences retrieved from GenBank was 95.0-100.0%. The percentage identity of the ompA sequence of the 15 Taiwanese strains and eight reference strains amplified in this study and two other sequences retrieved from GenBank was 88.1-100.0%. Phylogenetic analysis based on the 16S rRNA gene showed that all the R. anatipestifer strains fell into a single cluster. It is concluded that the 16S rRNA gene-based PCR is suitable for the screening of R. anatipestifer infections. Phylogenetic analysis of the ompA of R. anatipestifer resulted in three different clusters, while seven clusters were found when the derived amino acid sequence was the basis of analysis. No apparent cluster was found using the criteria of host, isolate serotype, the year or location of isolation.

Amino Acid Sequence↗

The use of bouts and frequencies in the evaluation of hand preferences for a coordinated bimanual task in chimpanzees (Pan troglodytes): an empirical study comparing two different indices of laterality.

Hand preferences for a coordinated bimanual task were assessed in 109 chimpanzees (Pan troglodytes). Hand preference was evaluated for 4 test sessions using bouts and frequencies of hand use to compare the sensitivity of each level of analysis in evaluating individual variation in handedness. Overall, significant population-level right-handedness was found using several different measures of hand use. Handedness indices based on bouts and frequencies were highly and significantly correlated. Moreover, hand preferences were consistent across tests despite efforts to situationally bias preference during each test. Taken together, these data do not support the view that bouts are a better level of analysis for evaluating hand preference. The results further suggest that hand preferences for coordinated bimanual actions are not influenced by situational factors and may reflect an inherent specialization of the left hemisphere for motor skill.

Animals↗

Forelimb segment length proportions in extant hominoids and Australopithecus afarensis.

Forelimb proportions have been used to infer locomotor adaptation in Australopithecus afarensis. However, little is known about proportions among individual forelimb segments in extant or fossil hominoids. The partial A. afarensis skeleton A.L. 438-1 and the more complete skeleton A.L. 288-1 provide the opportunity to assess relative length of the arm, forearm, wrist, and palm. We compare scaling relationships between pairs of forelimb bones of extant hominoids and A. afarensis, and length of individual forelimb elements to a body size surrogate. Hylobatids, and to a lesser extent orangutans, have the longest forelimb bones relative to size, although the carpus varies little among taxa, perhaps due to functional constraints of the wrist. Pan species are unique in having long metacarpals relative to ulnar length, demonstrating that they probably differ from the common chimp-human ancestor, and also that developmental mechanisms can be altered to results in differential growth of individual forelimb segments. A. afarensis has no forelimb bones that are significantly longer than those of humans for its size. It falls within the range of variation seen in modern humans for all comparisons relative to size, but appears to differ from the typical human brachial index due to a slightly shorter humerus and/or slightly longer ulna. It has short metacarpals like humans only among hominoids. Thus, while Pan may have elongated its metacarpus relative to ulnar length, A. afarensis may have reduced the length of its metacarpals and possibly its humerus relative to body size from the primitive condition.

Adaptation, Physiological↗

Heterochrony and geometric morphometrics: a comparison of cranial growth in Pan paniscus versus Pan troglodytes.

Heterochrony, the classic framework in which to study ontogeny and phylogeny, in essence relies on a univariate concept of shape. Though principal component (PC) plots of multivariate shape data seem to resemble classical bivariate allometric plots, the language of heterochrony cannot be translated directly into general multivariate methodology. We simulate idealized multivariate ontogenetic trajectories and explore their appearance in PC plots of shape space and size-shape space. Only if the trajectories of two related species lie along exactly the same path in shape space can the classic terminology of heterochrony apply and pure dissociation of size change against shape change be detected. Regional heterochrony--the variation of apparent heterochrony by region--implies a dissociation of local growth fields and cannot be identified in an overall PC analysis. We exemplify a geometric morphometric approach to these issues using adult and subadult crania of 48 Pan paniscus and 47 Pan troglodytes specimens. On each specimen, we digitized 47 landmarks and 144 semilandmarks on facial curves and the external neurocranial surface. We reject the hypothesis of global heterochrony in the cranium of Pan as well as regional heterochrony for the lower face, the upper face, and the neurocranium.

Aging↗

Why is silver catalytically active for NO reduction? A unique pathway via an inverted (NO)2 dimer.

NO reduction on the noble metal Ag has been studied using density functional theory calculations. It was found that monomeric NO dissociation is subject to prohibitive barriers on Ag metal and is thus unlikely to account for the experimental observations for NO reduction over Ag-based catalysts. For the first time, a mechanism via an inverted (NO)(2) dimer is identified, which can explain both the high activity and the selectivity of this catalytic system. N(2)O is the major reduction product of the inverted (NO)(2) dimer, in accord with experiment. The physical origin of the Ag metallic state as a good catalyst is furthermore identified: Ag surfaces, including small clusters, have little or no covalent bonding ability but can bond ionically with adsorbates. We conclude that the variation of the ionic bonding strength of Ag toward different reactants determines its catalytic selectivity.

Journal Article↗

Quantitative measurement of indomethacin crystallinity in indomethacin-silica gel binary system using differential scanning calorimetry and X-ray powder diffractometry.

Differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRPD) methods were developed for the quantitative analysis of the crystallinity of indomethacin (IMC) in IMC and silica gel (SG) binary system. The DSC calibration curve exhibited better linearity than that of XRPD. No phase transformation occurred in the IMC-SG mixtures during DSC measurement. The major sources of error in DSC measurements were inhomogeneous mixing and sampling. Analyzing the amount of IMC in the mixtures using high-performance liquid chromatography (HPLC) could reduce the sampling error. DSC demonstrated greater sensitivity and had less variation in measurement than XRPD in quantifying crystalline IMC in the IMC-SG binary system.

Calibration↗

[Clinical significance of the changes in interpeak latency of brainstem auditory evoked potentials in patients with cerebellopontine angle tumors].

Brainstem auditory evoked potentials (BAEP) were recorded and studied in 21 cases of cerebellopontine angle tumors (CPATs) identified with CT/operations. 111 healthy volunteers with 207 normal hearing ears served as controls. In the main the results indicated that there was an average significant increase of the III-V IPL in comparison with the III-V/I-III IPL on contralateral side. This finding suggested that as a result of its displacement of the brainstem to the opposite side, stem from the contralateral bony structure, when CPAT was suspected. Since individual variations exist especially in aged persons, interpretation in clinical practice had still to be individualized.

Adult↗

Single haplotype analysis demonstrates rapid evolution of the killer immunoglobulin-like receptor (KIR) loci in primates.

The human killer immunoglobulin-like receptors (KIR) are encoded within the Leukocyte Receptor Complex (LRC) on chromosome 19q13.4. Here we report the comparative genomic analysis of single KIR haplotypes in two other primates. In the common chimpanzee (Pan troglodytes), seven KIR genes (ptKIRnewI, ptKIRnewII, ptKIR2DL5, ptKIRnewIII, ptKIR3DP1, ptKIR2DL4, ptKIR3DL1/2) have been identified, and five KIR genes (mmKIRnewI, mmKIR1D, mmKIR2DL4, mmKIR3DL10, mmKIR3DL1) are present in the haplotype sequenced for the rhesus macaque (Macaca mulatta). Additional cDNA analysis confirms the genes predicted from the genomic sequence and reveals the presence of a fifth novel KIR gene (mmKIRnewII) in the second haplotype of the rhesus macaque. While all known human haplotypes contain both activating and inhibitory KIR genes, only inhibitory KIR genes (characterized by long cytoplasmic tails) were found by in silico and cDNA analyses in the two primate haplotypes studied here. Comparison of the two human and the two non-human primate haplotypes demonstrates rapid diversification of the KIR gene family members, many of which have diverged in a species-specific manner. An analysis of the intronic regions of the two non-human primates reveals the presence of ancient repeat elements, which are indicative of the duplication events that have taken place since the last common ancestor.

Amino Acid Sequence↗

Interspecific variation at the Y-linked RPS4Y locus in hominoids: implications for phylogeny.

Within- and between-species variation in restriction endonuclease recognition sites was examined at the Y-linked RPS4Y locus of six hominoid species: human (Homo sapiens), gorilla (Gorilla gorilla), chimpanzee (Pan troglodytes), bonobo (Pan paniscus), orangutan (Pongo pygmaeus), and gibbon (Hylobates lar). RPS4Y is an expressed gene that maps to the non-recombining region of the Y chromosome. An approximately 1,490 base pair fragment of the RPS4Y gene, including all of intron 3, was amplified by PCR from DNA extracted from each of the six species. Forty-seven restriction sites were identified on the six-species composite map derived from double-digest restriction analyses of the amplified fragment. As expected, maximum parsimony analysis indicated that chimpanzee and bonobo are the two most closely related living hominoids. The same analysis suggested that the closest living relative of Homo is Gorilla, not Pan, although support for this relationship was relatively weak. These results disagree with recently published phylogenies based on analyses of mtDNA sequences (Horai et al. [1995] Proc. Natl. Acad. Sci. U.S.A. 88:7401-7404) and the Y-linked ZFY locus (Dorit et al. [1995] Science 268:1183-1185). A combined data set derived from three distinct Y-linked loci-RPS4Y, SRY, and ZFY-was also analyzed. The maximum parsimony topology for the combined data provided only weak support for a shared common ancestor for Homo and Pan subsequent to divergence from the Gorilla lineage. Taken together, the data from the Y chromosome do not provide unequivocal support for any single, dichotomously branching species tree linking Homo, Pan, and Gorilla.

Animals↗

Antibodies raised to short synthetic peptides with sequences derived from HIV-1 SF2 gp120 can both neutralize and enhance HIV-1 SF13: a later variant isolated from the same host.

HIV-1 SF13 emerged in a patient with immunity to HIV-1 SF2. This study determined the effect of antibodies raised to HIV-1 SF2 on the replication of the later variant. Antisera in rats were raised previously to a complete set of overlapping, synthetic 15mer peptides following the sequence of HIV-1 SF2 gp120. These sera have now been used in neutralization and enhancement assays against viruses derived from molecular clones of both variants. The sets of peptides inducing neutralizing antibodies to the two variants overlap. Antibodies to the third variable region of HIV-1 SF2 only neutralize the homologous virus whereas those to the second and fourth variable regions neutralize both variants. In contrast, the sets of major epitopes involved in enhancement do not overlap. Epitopes for both variants form two clusters when superimposed on the conformation of the conserved regions. To determine if antibodies with the potential to enhance or neutralize HIV-1 SF2 change over time in infected individuals sera from chimpanzees were used because no material was still available from the original patient. Antibodies to HIV-1 SF2 neutralizing epitopes and HIV-1 SF13 enhancing epitopes were present in the circulation of chimpanzees infected with HIV-1 SF2. Once antibodies to the neutralizing epitopes were induced they persisted whereas antibodies to the enhancing epitopes varied with time after infection. Conditions may therefore exist within individual hosts where not only neutralizing but also enhancing antibodies have the potential to contribute to the selection pressure operating on the circulating population of polymorphic variants.

Animals↗

Immunohistochemical labeling of the mu opioid receptor carboxy terminal splice variant mMOR-1B4 in the mouse central nervous system.

The mu opioid receptor gene Oprm is alternatively spliced into many variants, providing for the multiplicity of mu opioid receptor subtypes. One of the mouse variants, mMOR-1B4, is unique in that it displays high affinity towards a wide range of mu opioid receptor antagonists, but poor affinity towards most classical mu opioid agonists. The present study examined the immunohistochemical distribution of the mMOR-1B4 variant in mouse brain and spinal cord. mMOR-1B4-like immunoreactivity (mMOR-1B4-LI) was enriched in many regions of the brain, spinal cord and in the dorsal root ganglia. Some of the structures showing prominent mMOR-1B4-LI include the olfactory bulb, cerebral cortex, bed nucleus of stria terminalis, hippocampus, habenular nucleus, amygdala, thalamus, hypothalamus, medium eminence, substantia nigra, ventral tegmental area, oculomotor nucleus, red nucleus, raphe nuclei, periaqueductal gray, locus coeruleus, trigeminal nucleus, reticular formation, area postrema and Purkinje cell layer and deep nuclei of cerebellum. mMOR-1B4-LI was present in afferent neurons of the dorsal root ganglia and their projecting fibers into the superficial laminae of the spinal dorsal horn. Some motor neurons in the anterior horn of the spinal cord also were immunopositive. The overall distribution of mMOR-1B4-LI in the central nervous system is distinguishable from previously characterized variants such as MOR-1-LI, MOR-1C-LI and exon-11-LI. These studies provide evidence for the region- and neuron-specific processing of the Oprm gene and support the possibility of functional differences among the variants.

Alternative Splicing↗

Persistent hepatitis C virus infection in a chimpanzee is associated with emergence of a cytotoxic T lymphocyte escape variant.

Hepatitis C virus (HCV) establishes a persistent infection in humans and chimpanzees despite the presence of virus-specific, class I major histocompatibility complex-restricted CD8+ cytotoxic T lymphocytes (CTLs) in the liver. The data presented here demonstrate that CTLs directed against a conserved epitope in the HCV nonstructural 3 protein persist in the liver of a chronically infected chimpanzee for at least 2 years after infection. However, these CTLs did not recognize the HCV quasi-species present in the plasma of this animal at week 16 postinfection or at later time points. Escape from the CTL response was facilitated by an aspartic acid to glutamic acid (D-->E) substitution at amino acid position 1449 in all HCV genomes that were sequenced. The results of this study strongly support the concept that CTL responses can select for variant viruses with an enhanced ability to persist in a host and have important implications for the design of vaccines against HCV.

Amino Acid Sequence↗

Comparison of Vpu sequences from diverse geographical isolates of HIV type 1 identifies the presence of highly variable domains, additional invariant amino acids, and a signature sequence motif common to subtype C isolates.

We compared the Vpu sequences from 101 strains of HIV-1 isolated from diverse geographical regions and various subtypes in order to identify regions of high variability, and those amino acid residues that were highly conserved or invariant. In addition to the highly conserved casein kinase II (CKII) phosphorylation sites, our analysis identified additional invariant residues in the transmembrane domain and in the first and second alpha-helical domains. Our analysis revealed that all subtype C sequences had a conserved LRLL motif at the C terminus that was also found in A/C intersubtype recombinants. While our analysis demonstrated the conservation of CKII domains in HIV-1 group M and O isolates, the number of potential CKII phosphorylation sites was variable in SIVcpz sequences. The results of this study will provide a basis for future mutagenesis studies to examine the role of certain amino acid residues in the structure and function of Vpu.

Amino Acid Motifs↗