Der Zusammenhang zwischen Lokomotionsweise,Begattungsstellung und Penislänge bei Säugetieren1

Penis length, copulation and locomotion: Their relationship to each other in Mammals A relationship between the mode of locomotion, copulatory position and length of the male copulative organ has been found in all groups of Mammalia. In this paper particular emphasis is given to the orders of the Testiconda, while the Testiphaena receive only brief account (for explanation of terms see Frey 1991 a). Results from my previous antomical study are utilized that are essential for assessing the respective modes of locomotion (Frey 1991b). Information on penis length and copulatory position are taken from the literature and evaluated. Small and middle-sized Testiphaena, which represent the majority of mammals, are capable of a dynamic sagittal bending in the trunk, which is evidenced both in the galloping mode of locomotion and in the usual mammalian copulatory position (mounting). A sagittal bending of the trunk enables the male to bring his genital region into close proximity of the female's genital opening. In this case, a short penis is sufficient to ensure sperm transfer. The construction of the trunk in the Testiconda (excepting the Hyracoidea) entirely or nearly entirely prevents the sagittal bending. This is largely due to rigidity of the lumbar region or insufficient (dynamic) muscular control. The immobilization and/or the functional weakness of the lumbar region are derived from different anatomical conditions. 1. Shortening of the lumbar region, e.g., Tachyglossidae, Elephantidae, Sirenia; 2. Tightening of the lumbar region by tendons and muscles, e. g., Macroscelididae, Cetacea; 3. Xenarthry of the lumbar vertebrae and a double connection of the pelvis on the vertebral column, e. e., Bradypodidae, Myrmeco-phagidae; 4. The lumbar region may be flexible but the hypaxial muscles too short and weak, e. g., Tenrecinae, Soricidae, Erinaceidae. Lumbar rigidity or insufficient muscular control in the lumbar region, resulting from any of these conditions, makes copulation difficult by restricting close approximation of the male and female genitals. Most Testiconda compensate for this by having a long penis. The same also applies for large-sized Testiphaena. Although these animals have retained the ability to gallop, the flexibility of their trunk is restricted and mostly localized in a single joint due to the great body mass and the constructive constraints necessary for increased stability. A long penis is not the only way to compensate for the absence of sagittal flexion. A phylogenetic change in the copulatory posture also solves the problem as seen in the Myr-mecophagidae and Bradypodidae (both Testiconda) which are equipped with a secondarily short-enedpenis. The permanently aquatic testicondid mammals (Sirenia and Cetacea) cannot copulate in the usual mammalian mount position. This is largely due to the phylogenetic reduction and reconstruction of the extremities as well as the secondary evolution of a powerful tail. Sagittal movements of the heavily musculated tail act upon the more or less rigid trunk to provide for a “rear drive” locomotion. Both a change in the copulatory position and a long penis were necessary for these aquatic mammals. The only Testiconda in which a marked dynamic sagittal flexibility of the trunk is developed -the Hyracoidea - are characterized by a short penis. On the whole, the relationship between the mode of locomotion, copulatory position and penis length within the mammalia is confirmed. A rigid lumbar region as opposed to a sagittally flexible, presumably represents the primitive condition among mammals. All Testiconda have     

Larvaler «Triähanismus» Und die Evolution alternativer Entwicklungszyklen bei einem saprobionten Nematoden: Rhabditis (Pelodera) orbitalis (Nematoda) als Larvalparasit im Auge von Mäusen1

Larval triphenism and the evolution of alternative life-cycles in a microbotrophic nematode: Rhabditis (P.) orbitalis – a larval parasite in the eye orbits of murid rodents Along with the normal third stage larva and the resistant dauerlarva, Rh. orbitalis posesses an infective larva, which is an obligate parasite in the eye orbits of mice and voles. Dauerlarvae as well as infective larvae develop from a common pre-stage («girdle-larva»), determined by the quality of food stored in the intestinal cells. – Dauerlarvae may tolerate desiccation (at room-temperature and -humidity) up to 4 weeks. If stored in tap water (at 6°C), they will survive for some month being able to restore development. – Infective larvae never survive desiccation but can also be stored in tap water at low temperatures. Food uptake from the lachrymal fluid of a host is needed prior to restoring development. The phenomenon involved is referred to as a necessary adaptation to the ecological conditions in the rodents' nests. It is also pointed out to the different strategies of other parasitic nematode species.     

Modulating EGFR-MTORC1-autophagy as a potential therapy for persistent fetal vasculature (PFV) disease

ABSTRACT

Persistent fetal vasculature (PFV) is a human disease that results from failure of the fetal vasculature to regress normally. The regulatory mechanisms responsible for fetal vascular regression remain obscure, as does the underlying cause of regression failure. However, there are a few animal models that mimic the clinical manifestations of human PFV, which can be used to study different aspects of the disease. One such model is the Nuc1 rat model that arose from a spontaneous mutation in the Cryba1 (crystallin, beta 1) gene and exhibits complete failure of the hyaloid vasculature to regress. Our studies with the Nuc1 rat indicate that macroautophagy/autophagy, a process in eukaryotic cells for degrading dysfunctional components to ensure cellular homeostasis, is severely impaired in Nuc1 ocular astrocytes. Further, we show that CRYBA1 interacts with EGFR (epidermal growth factor receptor) and that loss of this interaction in Nuc1 astrocytes increases EGFR levels. Moreover, our data also show a reduction in EGFR degradation in Nuc1 astrocytes compared to control cells that leads to over-activation of the mechanistic target of rapamycin kinase complex 1 (MTORC1) pathway. The impaired EGFR-MTORC1-autophagy signaling in Nuc1 astrocytes triggers abnormal proliferation and migration. The abnormally migrating astrocytes ensheath the hyaloid artery, contributing to the pathogenesis of PFV in Nuc1, by adversely affecting the vascular remodeling processes essential to regression of the fetal vasculature. Herein, we demonstrate in vivo that gefitinib (EGFR inhibitor) can rescue the PFV phenotype in Nuc1 and may serve as a novel therapy for PFV disease by modulating the EGFR-MTORC1-autophagy pathway.     

Mutations induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in the lacZ and cII genes of Muta™ Mouse

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) found in chewing tobacco, snuff, cigarettes, and cigars is a tobacco-specific nitrosamine and classified as a possible human carcinogen (Class 2B) by the International Agency for Research on Cancer (IARC). NNK given intraperitoneally was seen to induce lung and liver adenomas.To evaluate the genotoxicity of NNK in vivo, NNK was intraperitoneally administered to Muta™ Mouse at two concentrations (125 and 250 mg/kg, once a week for 4 weeks) followed by the measurement of mutant frequencies in the lacZ and cII genes from lung and liver in the same mice. Characterization of the types of the mutation was determined by sequencing the cII genes from mutant plaques. The mutant frequencies in both target genes from both organs dose-dependently increased up to 10 times compared to those of the control group. For the types of mutations, the ratio of the G:C to A:T mutation in the total number of mutants was less than the ratio of A:T to T:A and A:T to C:G transversion, contrary to a previous report [Cancer Res, 49 (1989) 5305]. The A:T to T:A transversion was the most highly induced mutation both in the lung and liver cII genes. The increasing rate of mutant frequencies in lung and liver over the vehicle control was 55 and 56 times, respectively, while the increasing rate of G:C to A:T transition was only 1.9 and 2.8 times, respectively.These observations show that NNK predominantly induces DNA adducts leading to A:T to T:A and/or A:T to C:G mutations in the transgene.     

Die Veränderung populationsdynamischer Parameter bei Gammarus tigrinus Sexton (Crustacea: Amphipoda) als Ausdruck subletaler Effekte durch die Wechselwirkung von Temperatur und cadmiumkontaminiertem Futter

Changes in the Population Dynamics of Gammarus tigrinus SEXTON (Crustacea: Amphipoda) as Expression of Sublethal Effects by Reciprocal Interactions of Temperature and Cadmium Enriched Food The population dynamics of Gammarus tigrinus SEXTON were studied in a flow-through system under semi-natural conditions over a period of 9 months. Elevated temperatures and Cadmiumenriched food alter lifespan of generations, growth rate, number of individuals and time to reach maturity, even before elevated Cadmium concentrations can be detected in the animals. Reciprocal interactions of Cadmium intake via food and/or water can be modified by the experimental design, because it depends on the experimental animals, on the Cadmium concentration and on the temperature regime with constant or cyclic conditions.     

Central and peripheral injections of ACTH (1–24) reduce fever in adrenalectomized rabbits

Central administration of ACTH (1-24) reduces fever in normal rabbits in doses that have no effect on afebrile body temperature. Previous experimental and clinical reports indicate that peripheral administration of both ACTH and corticosteroids reduces fever, and since central injection of corticosteroids can also lower fever it might be that the antipyretic effect of intracerebroventricular (ICV) ACTH (1-24) is due to adrenal stimulation. To learn whether this endogenous central peptide can produce antipyresis independently, ACTH (1-24) was injected ICV in bilaterally adrenalectomized (ADX) rabbits made febrile by IV injections of leukocytic pyrogen (LP). ACTH (250 ng) given ICV reduced fever in these animals and had a slight hypothermic effect when given to the same rabbits when they were afebrile. Doses of 25-75 ng reduced fever without influencing normal body temperature. Intravenous injections of ACTH (2.5 micrograms) also lowered fever caused by IV LP in ADX rabbits. The present findings raise the possibility that release of endogenous central ACTH, and perhaps entry into the brain of circulating ACTH, the release of which is known to increase in fever, limits the magnitude of the febrile response by influencing central temperature controls.     

PDK4 Protein Promotes Tumorigenesis through Activation of cAMP-response Element-binding Protein (CREB)-Ras Homolog Enriched in Brain (RHEB)-mTORC1 Signaling Cascade

Mechanistic target of rapamycin (mTOR) integrates multiple extracellular and intracellular signals to regulate cell growth and survival. Hyperactivation of mTOR has been observed in various cancers. Regulation of mTOR activity is thus of importance in physiological processes and tumor development. Here, we present pyruvate dehydrogenase kinase 4 (PDK4) as a novel regulator of mTORC1 signaling. mTORC1 activity was augmented with PDK4 overexpression and reduced by PDK4 suppression in various cell lines. Furthermore, PDK4 bound to cAMP-response element-binding protein (CREB) and prevented its degradation. The enhanced CREB consequently transactivated the expression of Ras homolog enriched in brain (RHEB), a direct key activator of mTORC1, independent of AMP-activated protein kinase or tuberous sclerosis complex protein 2. PDK4 potentiated the mTORC1 effectors hypoxia-inducible factor 1α and pyruvate kinase isozymes M2 and promoted aerobic glycolysis (Warburg effect). Knockdown of PDK4 suppressed the tumor development of cancer cells with activated mTORC1. The abundance of PDK4 dictated the responsiveness of cells to the mTOR inhibitor, rapamycin. Combinatory suppression of mTOR and PDK4 exerted synergistic inhibition on cancer cell proliferation. Therefore, PDK4 promotes tumorigenesis through activation of the CREB-RHEB-mTORC1 signaling cascade.     

Ab initio-based vibrational analysis of α-poly(L-alanine)

Polarized ir and Raman spectra have been obtained on oriented films of α-helical poly(L -alanine) (α-PLA) and its N-deuterated derivative. These improved spectra permit a more complete assignment of observed bands to A-, E₁-, and E₂-species modes. A new empirical force field has been refined, based on ab initio force fields of N-methylacetamide and L -alanyl-L -alanine, which reproduces observed frequencies above 200 cm⁻¹ to less than 5 cm⁻¹. A new transition dipole coupling treatment avoids the weak coupling and perturbation approximations, and can now account for the newly observed and reassigned amide I (E₂) mode. As a result of this improved force field, several other observed bands have also been reassigned. © 1998 John Wiley & Sons, Inc. Biopoly 46: 283–317, 1998     

A New Species of Kudoa (Myxosporidea: Chloromyxidae) from the Spot,Leiostomus xanthurus Lacépède,in Clear Lake,Texas*

SYNOPSIS. Kudoa branchiata sp. n. (Myxosporidea: Chloromyxidae) is described from the gills of the marine sciaenid fish, Leiostomus xanthurus Lacépède, from Clear Lake, Texas. Twelve of the 429 hosts examined from 10 September 1970 to 28 April 1971, were infected. Eight of the 12 infected fish were collected in February and March 1971—a period during which only 13% of the total host sample was taken. The mean total length of infected hosts was 149 mm, with a range of 112–185 mm. The mean number of myxosporidean cysts per infected host was 3.5, with a range of 1–11.     

Changes in photosynthetic capacity and polypeptide patterns during natural senescence and rejuvenation of <Emphasis Type="Italic">Cucurbita pepo</Emphasis> L. (zucchini) cotyledons

Natural senescence of Cucurbita pepo (zucchini) cotyledons was accompanied by a gradual degradation of reserve proteins (globulins) and an intensive decrease in the content of both large subunit (LSU) and small subunit (SSU) of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco). The net photosynthetic rate, the primary photochemical activity of PSII, estimated by the variable fluorescence (F_v)/maximal fluorescence (F_m) ratio (F_v/F_m) and the actual quantum yield of PSII electron transport in the light-adapted state (ΦPSII) also progressively decreased during natural senescence. In contrast, the fraction of the absorbed light energy, which is not used for photochemistry (LNU) increased with progression of senescence. The decline in the photosynthetic rate started earlier in ontogenesis compared with the down-regulation of the functional activity of PSII, thus suggesting the existence of protective mechanisms which maintain higher efficiency of the photochemical electron transport reactions of photosynthesis compared with the dark reactions of the Calvin cycle during earlier stages of natural senescence. Decapitation of the epicotyl above the senescing cotyledons resulted in full recovery of the polypeptide profile in the rejuvenated cotyledons. In addition, the photosynthetic rate increased reaching values that exceeded those measured in juvenile cotyledons. The photochemical efficiency of PSII also gradually recovered, although it did not reach the maximum values measured in the presenescent cotyledons.     

Discovery of a non-toxic [1,2,4]triazolo[1,5-a]pyrimidin-7-one (WS-10) that modulates ABCB1-mediated multidrug resistance (MDR)

Multidrug resistance (MDR) has been shown to reduce the effectiveness of chemotherapy. Strategies to overcoming MDR have been widely explored in the last decades, leading to a generation of numerous small molecules targeting ABC and MRP transporters. Among the ABC family, ABCB1 plays key roles in the development of drug resistance and is the most well studied. In this work, we report the discovery of non-toxic [1,2,4]triazolo[1,5-a]pyrimidin-7-one (WS-10) from our structurally diverse in-house compound collection that selectively modulates ABCB1-mediated multidrug resistance. WS-10 enhanced the intracellular accumulation of paclitaxel in SW620/Ad300 cells, but did not affect the expression of ABCB1 Protein and ABCB1 localization. The cellular thermal shift assay (CETSA) showed that WS-10 was able to bind to ABCB1, which could be responsible for the reversal effect of WS-10 toward paclitaxel and doxorubicin in SW620/Ad300 cells. Docking simulations were performed to show the possible binding modes of WS-10 within ABCB1 transporter. To conclude, WS-10 could be used as a template for designing new ABCB1 modulators to overcome ABCB1-mediated multidrug resistance.     

Pharmacological comparison of bPTH-(1–34) and other hypotensive peptides in the dog

The purpose of the present study was to compare the potency, effectiveness and duration of action of synthetic bPTH-(1–34) with those of other known hypotensive peptides in the anesthetized dog. Of sixteen peptides tested in the present study only 8 were demonstrated to possess hypotensive activity. While bPTH-(1–34) was one of the least potent of the hypotensive peptides, it was equal to or greater than the other peptides in terms of effectiveness and duration of action. Of all the peptides studied, substance P and eledoisin were the most potent in terms of their hypotensive action. It is suggested that perhaps substance P and eledoisin might act at a different site or through different mechanisms than do vasoactive intestinal peptide (V.I.P.), corticotropin inhibiting peptide (C.I.P.), neurotensin, xenopsin, bradykinin and bPTH-(1–34).     

Pharmacological comparison of bPTH-(1–34) and other hypotensive peptides in the dog

The purpose of the present study was to compare the potency, effectiveness and duration of action of synthetic bPTH-(1–34) with those of other known hypotensive peptides in the anesthetized dog. Of sixteen peptides tested in the present study only 8 were demonstrated to possess hypotensive activity. While bPTH-(1–34) was one of the least potent of the hypotensive peptides, it was equal to or greater than the other peptides in terms of effectiveness and duration of action. Of all the peptides studied, substance P and eledoisin were the most potent in terms of their hypotensive action. It is suggested that perhaps substance P and eledoisin might act at a different site or through different mechanisms than do vasoactive intestinal peptide (V.I.P.), corticotropin inhibiting peptide (C.I.P.), neurotensin, xenopsin, bradykinin and bPTH-(1–34).     

Analysis of warfarin enantiomers: Chromatographic separation of six stereoisomeric esters prepared from (−)-(1S,2R,4R)-endo-1,4,5,6,7,7-hexachlorobicyclo[2.2.1]hept-5-ene-2- carboxylic acid

Reaction of rac-warfarin, (?)-(1S,2R,4R)-endo-1,4,5,6,7,7-hexachlorobicyclo[2.2.1]hept-5-ene-2- carboxylic acid [(?)-HCA] and carbodiimide reagents gave two noncyclic ketonic diastereoisomeric derivatives whereas rac-warfarin and (?)-HCA acid chloride with 4-(dimethylamino)pyridine gave four cyclic hemiketal diastereoisomeric ester derivatives. The structure and stereochemistry of diastereoisomeric esters prepared from warfarin and p-chlorowarfarin were determined from ¹H- and ¹³C-NMR spectra, mass spectra, and hydrolysis to warfarin and p-chlorowarfarin enantiomers. The structure and stereochemistry of one of the cyclic hemiketal diastereoisomeric derivatives of warfarin are supported by an X-ray crystallographic determination. Mechanisms for the formation of all products are proposed. © 1994 Wiley-Liss, Inc.     

Anionic effects on the formation of tridentate 4′-chloro-2,2′:6′,2″-terpyridine copper(II) complexes having 1:1 or 1:2 ratio of metal and ligand and their crystal symmetry

A facile synthetic procedure has been used to prepare one five-coordinate and four six-coordinate copper(II) complexes of 4′-chloro-2,2′:6′,2″-terpyridine (tpyCl) ligand with different counterions (, , , , and ) in high yields. They are formulated as [Cu(tpyCl-κ³N,N′,N′′)(SO₄-κO)(H₂O-κO)] · 2H₂O (1), trans-[Cu(tpyCl-κ³N,N′,N″)(NO₃-κO)₂(H₂O-κO)] (2), [Cu(tpyCl-κ³N,N′,N″)₂](BF₄)₂ (3), [Cu(tpyCl-κ³N,N′,N″)₂](PF₆)₂ (4) and [Cu(tpyCl-κ³N,N′,N″)₂](ClO₄)₂ (5) and versatile interactions in supramolecular level including coordinative bonding, O-H?O, O-H?Cl, C-H?F, and C-H?Cl hydrogen bonding, π-π stacking play essential roles in forming different frameworks of 1-5. It is concluded that the difference of coordination abilities of the counterions used and the experimental conditions codominate the resulting complexes with 1:1 or 1:2 ratio of metal and ligand.