trans-dominant mutations in the GPR1 gene cause high sensitivity to acetic acid and ethanol in the yeast Yarrowia lipolytica

Acetate non-utilizing strains harbouring trans-dominant mutations in the GPR1 gene (GPR1(d)) of the dimorphic yeast Yarrowia lipolytica have been selected and characterized. These mutants are highly sensitive to low concentrations of acetic acid and ethanol, even in presence of glucose. The toxic effect of acetic acid is pH-dependent and has the strongest effect at low pH. In contrast, the action of ethanol is pH-independent. One GPR1(d) mutant has been detected that was highly sensitive to acetic acid but could still grow on ethanol, which indicates putative differences in the function of the GPR1 gene product in the sensitivity to acetic acid and ethanol. The GPR1(d) mutants exhibit a complex pleiotropic phenotype. The mutations cause changed colony morphology as well as dimorphism of cells, and induce early cell death during growth on glucose, even without the presence of dicarbon compounds. Composition of intracellular membranes, as well as morphology of vacuole and mitochondria, were strongly changed. Back-crosses with wild-type strains and analysis of recombinant strains have shown that the expression of the pleiotropic phenotype depends on the site of mutation in the GPR1 gene, as well as on the genetic background of the strain harbouring the responsive mutation. Our data suggest that Gpr1p is involved in a general response of cells to the toxic action of dicarbon compounds like acetic acid and ethanol.     

OTA based on CMOS inverters and application in the design of tunable bandpass filter

A new operational transconductance amplifier (OTA) builds with CMOS inverters only is proposed in this paper. Simulations with typical BSIM3V3 parameters of a 0.35 μm CMOS process have shown a 3.56 GHz gain-bandwidth product under 2.5 V supply voltage. The corresponding total harmonic distortion is equal to 0.46% for 2 V peak–peak differential output voltage. At the same supply voltage, the circuit can provided at each output a voltage swing of 2.25 V peak–peak. From V_DD = 2 V to V_DD = 2.5 V the differential transconductance varies from 72 to 108.4 μΩ⁻¹. The corresponding common mode rejection ratio and the total power consumption are always lower than −31 dBc and 800 μW, respectively. Typical application of a biquad filter is proposed to illustrate the circuit capabilities.     

The clinical diagnosis of major congenital abnormalities of the fetal central nervous system

During the ten years between 1965 and 1974, 207 infants with a major congenital abnormality of the central nervous system were born at Mill Road Maternity Hospital, Liverpool; open neural tube defects occurred in 92 per cent of cases. Only cases of anencephaly were frequently diagnosed clinically before labour and this was rarely so for spina bifida alone. Only 11 patients (5-3 per cent) had previously been delivered of an affected infant. The routine screening of pregnant patients is briefly discussed.     

Collateral splanchnic circulation (author''s transl)]

The structure of developing rat testes was studied by light and electron microscopy. Ultrastructural differentiation of Sertoli and Leydig cells was followed from 14 days of gestation through birth. Specialized morphology in Sertoli cells was first seen at 16 days of gestation. In these cells the rough endoplasmic reticulum increased and became organized as numerous short cisternae loaded with a homogenous material. Typical Leydig cells were found among the stromal cells, around day 17 of gestation. There is good correlation between the time of appearance of ultrastructural specialization and published data on secretory capacity of the fetal testes, in respect to the inhibition and differentiation of the Müllerian and Wolffian ducts.     

Lymphocytocidal lymphocyte trapping by human lymph node cells: a tissue culture-ultrastructural study

An ultrastructural study was carried out on 25 lymphocyte-trapping cells selected from tissue cultures of human axillary lymph nodes. The trapping cells contained several hundred intravacuolar lymphocytes, most of which showed degenerative changes. The principal findings are: (a) a braod spectrum of lymphocyte degeneration; (b) a consistent pattern of lymphocyte degeneration beginning with perinuclear vacuoles and ending with breakdown of the nuclear envelope; (c) the viable lymphocytes tended to be located in a juxtanuclear region; (d) a lysosomal relationship was suggested for lymphocyte degeneration but not for lymphocyte trapping; and (e) degeneration of the trapping cell, or lymphocytes associated with other cells, was not observed. The sequence of degenerative changes differs from those reported for several classes of lymphocytocidal agents. There were no morphologic properties of the trapping cell which served to identify it more specifically. The findings, together with previous time-lapse film observations, warrant further investigation of the hypothesis that lymphocytocidal lymphocyte trapping may be involved in the control of lymphocyte populations.     

A boxer dog with chronic hypertrophic gastritis resembling Menetrier's disease in man

Chronic hypertrophic gastritis in a 7-year-old Boxer dog is described. This gastritis resembles Menetrier's disease in man. The dog was emaciated, lethargic, vomiting and had a poor appetite over a 4-month period. There was anaemia, and the blood smear was characterized by hypochromasia, strong anisoplania and striking poikilocytosis. There was a protein loss and at a later stage of the disease, a hypoalbuminaemia. On gastroscopic examination the plicae gastricae were numerous and strongly marked; moreover, they were granulated with numerous small haemorrhages. Radiographically, the stomach had a marked folding, primarily at the greater curvature. The passage of contrast medium from the stomach into the duodenum was strongly retarded. The pathological findings included macroscopical folding caused by local gland cell hyperplasia in the body as well as the pylorus, foveolar hyperplasia and, in the fundus and in the corpus near the greater curvature, folding of the muscularis mucosae and the submucosa. A superficial gastritis was found particularly in the fundus and corpus, whereas the pyloric antrum showed a more diffuse inflammation.     

Early unconjugated hyperbilirubinaemia after paracetamol overdosage

A rapid increase of predominantly unconjugated bilirubin in the blood -- which was not due to haemolysis -- was observed in 38 of 60 patients who had taken an overdose of paracetamol. Studies in the rat given an overdose of the drug showed that within 24 hours there was a striking reduction in the activity of bilirubin glucuronyl-transferase and the content of cytochrome P.450 in the liver. It is suggested that such early damage of the hepatic endoplasmic reticulum contributes to the hyperbilirubinaemia of paracetamol poisoning.     

Selective isolation of reversible cold sensitive variants from Chinese hamster ovary cell cultures

The fine structure and cellular associations of the large pigment cells (LPC's) of the compound eye of the house fly were studied with high voltage and conventional electron microscopy. Depending on the sector of the compound eye, the facets are either rectangular or hexagonal. The underside of each facet has indentations exactly aligned with those on top into which inserts an angulated sleeve of LPC's. Under the rectangular lens facet 6 or 8 small compact (in cross section) LPC's join four elongate LPC's. Clusters of compact cells alternate in this ring with elongate ones. Compact cells compress together and become quadrangular (in cross section) several microns below their insertion into the lens and form "building block" corners while elongate cells form "side rails" for the rectangular type of distal pseudocone enclosure. Beneath hexagonal facets all LPC's are rather elongate with out corner cells. In both facet types LPC's enclose the pseudocone for a longitudinal distance of 4 mum and then are displaced as bordering cells by a sleeve of two corneal pigment cells (CPC's), each of which encloses half of the proximal pseudocone. For the following 6 mum of longitudinal distance these concentric sleeves of CPC's and LPC's form a double layer around the pseudocone. At about 10 mum below lens base the two sleeves separate; LPC's become attenuated and extend cable-like to the basement membrane and CPC's enclose the proximal pseudocone, Semper cells and distal retinula. The junction between lens and LPC's has critical structural value in that (1) this is the sole anchorage to the lens by the lengthy remainder of the ommatidium, and (2) LPC's enclose the semiliquid pseudocone in the most distal portion of the pseudocone. In addition to vertical support, the LPC's send out numerous lateral processes that make structural contact among themselves, with the corneal pigment cells and the photoreceptor cells. The structural features of this array are discussed relative to possible physiological roles.