Effect of crab effluent and scent of damaged conspecifics on feeding,growth, and shell morphology of the Atlantic dogwhelk Nucella lapillus (L.)

Juvenile Nucella lapillus of two different shell phenotypes, exposed shore and protected shore, were maintained in running seawater under each of three experimental conditions for 94 d: a) laboratory control, b) exposed to the effluent of crabs (Cancer pagurus) fed frozen fish (fish-crab), and c) exposed to the effluent of crabs fed live conspecific snails (snail-crab). Rates of barnacle consumption and rates of body weight change varied significantly between phenotypes and among experimental conditions. Individuals from the protected-shore consumed consistently fewer barnacles and grew consistently less than those from the exposed shore. Body weight increases in the fish-crab treatments were from 25 to 50% less than those in the controls and body weights in the snail-crab treatment either did not change or actually decreased. The perceived risk of predation thus appears to have a dramatic effect on the rates of feeding and growth of N. lapillus.At the end of the experiment, size-adjusted final shell weights for both phenotypes were consistently higher than controls (no crab) in both the fish-crab and snail-crab treatments. In addition, apertural tooth height, thickness of the lip, and retractability (i.e. the extent to which a snail could withdraw into its shell), with few exceptions all varied in an adaptive manner in response to the various risk treatments. Similar changes in the shell form of starved snails exposed to the same stimuli suggest very strongly that the morphological responses of both phenotypes were not just due to differences in rates of growth. These differences, at least in part, represented a direct cueing of the shell form of Nucella lapillus to differences in the perceived risk of predation. Somewhat surprisingly, the extent of phenotypic plasticity appeared to differ between the populations examined. Both field and laboratory evidence suggest that the exposed-shore population was much more labile morphologically than the protected-shore population.In many instances, particularly among starved snails, the development of antipredatory shell traits was greater in the fish-crab treatment than in the snail-crab treatment. Because the scent of crabs was present in both treatments, these results suggest a) that, at the frequency/concentration used in the experiments, the scent of damaged conspecifics may have been a supernormal stimulus and b) that the morphological response in these treatments might have been greater if the stimulus had been provided at a lower level.     

Adjuvant chemotherapy for breast cancer: side effects and quality of life.

In a trial of postoperative adjuvant chemotherapy women with primary breast cancer and spread to one or more axillary nodes were randomised to receive a six-month course of either the single agent chlorambucil or the five-drug combination of chlorambucil, methotrexate, fluorouracil, vincristine, and adriamycin. On completing the treatment 47 patients were asked to fill in questionnaires at home on the side effects of treatment and its influence on the quality of their life. Side effects including nausea, vomiting, malaise, and alopecia had been severe enough to interfere with their lifestyle in 9 (42%) of the patients who had received the single agent and 19 (79%) of those who had received multiple-drug treatment. Various other side effects were reported by a few patients. Seven (29%) of the patients who had received the multiple-drug schedule voluntarily added that the treatment had been "unbearable" or "could never be gone though again." The proportion of patients who had experienced severe side effects while receiving the treatment was considerable; hence such adjuvant chemotherapy is justifiable only if it will substantially improve a patient''s prognosis.     

SARS-CoV-2-specific T cells associate with inflammation and reduced lung function in pulmonary post-acute sequalae of SARS-CoV-2

As of January 2022, at least 60 million individuals are estimated to develop post-acute sequelae of SARS-CoV-2 (PASC) after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While elevated levels of SARS-CoV-2-specific T cells have been observed in non-specific PASC, little is known about their impact on pulmonary function which is compromised in the majority of these individuals. This study compares frequencies of SARS-CoV-2-specific T cells and inflammatory markers with lung function in participants with pulmonary PASC and resolved COVID-19 (RC). Compared to RC, participants with respiratory PASC had between 6- and 105-fold higher frequencies of IFN-γ- and TNF-α-producing SARS-CoV-2-specific CD4⁺ and CD8⁺ T cells in peripheral blood, and elevated levels of plasma CRP and IL-6. Importantly, in PASC participants the frequency of TNF-α-producing SARS-CoV-2-specific CD4⁺ and CD8⁺ T cells, which exhibited the highest levels of Ki67 indicating they were activity dividing, correlated positively with plasma IL-6 and negatively with measures of lung function, including forced expiratory volume in one second (FEV¹), while increased frequencies of IFN-γ-producing SARS-CoV-2-specific T cells associated with prolonged dyspnea. Statistical analyses stratified by age, number of comorbidities and hospitalization status demonstrated that none of these factors affect differences in the frequency of SARS-CoV-2 T cells and plasma IL-6 levels measured between PASC and RC cohorts. Taken together, these findings demonstrate elevated frequencies of SARS-CoV-2-specific T cells in individuals with pulmonary PASC are associated with increased systemic inflammation and decreased lung function, suggesting that SARS-CoV-2-specific T cells contribute to lingering pulmonary symptoms. These findings also provide mechanistic insight on the pathophysiology of PASC that can inform development of potential treatments to reduce symptom burden.     

An assessment of macroinvertebrate functional feeding groups as water quality indicators in the Buffalo River, eastern Cape Province, South Africa

The aim of this paper was to investigate the potential for using functional feeding groups (FFGs) as indicators of water quality conditions in rivers, using the Buffalo River, South Africa, as a specific example. Multivariate classification and ordination techniques were used to investigate species and FFG distributions in relation to a number of physico-chemical variables at 16 sites from the headwaters to the estuary of the Buffalo River.Two-way indicator species analysis (TWINSPAN) of species composition ranked most of the sites sequentially down the river, irrespective of water quality conditions. Ordination of FFGs from a set of riffle samples collected in mid-late summer showed only weak relationships between FFG distribution and water quality changes, except where variables changed sequentially down the river (e.g. pH and temperature). Individual species responses to water quality gradients were examined for nine riffle-dwelling species representing diverse FFGs. Following correspondence analysis of a matrix of environmental variables and species frequencies, some species showed strong associations with defined ranges of some variables. In particular, Adenophlebia auriculata (Leptophlebiidae, Ephemeroptera) from the headwater sampling site, was associated with low pH and low temperature. Simulium damnosum occurred under conditions of high turbidity, while Afronurus harrisoni was found under high concentrations of potassium, ammonium and nitrite ions.We conclude that although there was a distinct headwaters fauna in the Buffalo River, and sequential downstream changes in species composition, most FFGs (apart from shredders) were represented down the whole length of the river. FFG classifications are therefore unlikely to provide useful indications of water quality conditions in the Buffalo River.Using a categorical approach to classifying water quality variables, and by applying correspondence analysis to the resulting matrix, we recognised nine species that could be used to define water quality. These indicator species can be used to define tolerance ranges of the fauna for water quality conditions in different parts of the Buffalo river.     

Characterization of phospholipase C-mediated phosphatidylinositol degradation in rat heart ventricle

Phosphoinositide-specific phospholipase C (PI-PLC) activity was investigated in the rat heart ventricle. Incubation of ventricle homogenate or 100,000g supernatant fraction with [3H]myoinositol or [3H]arachidonate-labeled phosphatidylinositol in the presence of Ca2+ resulted in a decrease in phosphatidylinositol with a concomitant increase in water-soluble [3H]inositol phosphate or [3H]diglyceride, respectively. Total overt homogenate PI-PLC activity could be accounted for in the supernatant fraction. Neutral, zwitterionic, cationic, or anionic detergents did not unmask membrane-associated activity. While cytosolic phospholipase C was active against a pure phosphatidylinositol substrate in the presence of Ca2+, no hydrolytic activity was detected when phosphatidylinositol was presented as a component (4-5%) of a mixture of phospholipids. However, addition of deoxycholate to the incubation mixture (pH 6.5, Ca2+ 10(-3) M) containing mixed phospholipids resulted in the exclusive hydrolysis of inositol phospholipids. Ventricular supernatant phospholipase C-mediated phosphatidylinositol degradation has a sharp pH optimum at 5.5 and a specific requirement for Ca2+. Activity is maximal at 1 to 2 X 10(-3) M Ca2+, with inhibition occurring at higher levels. Under optimized conditions phosphatidylinositol is hydrolyzed at a rate of 20-25 nmol/min/mg protein. Multivalent cations inhibit Ca2+-dependent PI-PLC activity while monovalent cations and anions have no effect. There is no apparent selectivity for specific fatty acid moieties on phosphatidylinositol. Soluble PI-PLC is inhibited by sulfhydryl reagents, neomycin, mepacrine, trifluoperazine, and propranolol. Chlorpromazine, dibucaine, and tetracaine exert a biphasic influence, stimulating at lower and inhibiting at higher concentrations.     

Mechanisms of Salmonella pathogenesis in animal models

Animal models play an important role in understanding the mechanisms of bacterial pathogenesis. Here we review the recent studies of Salmonella infection in various animal models. Although mice are a classic animal model for Salmonella, mice do not normally get diarrhea, raising the question of how well the model represents normal human infection. However, pre-treatment of mice with oral streptomycin, which apparently reduces the normal microbiota, leads to an inflammatory diarrheal response upon oral infection with Salmonella. This has led to a re-evaluation of the role of various Salmonella virulence factors in colonization of the intestine and induction of diarrhea. Indeed, it is now clear that Salmonella purposefully induces inflammation, which leads to the production of both carbon sources and terminal electron acceptors by the host that allow Salmonella to outgrow the normal intestinal microbiota. Overall use of this modified mouse model provides a more nuanced understanding of Salmonella intestinal infection in the context of the microbiota with implications for the ability to predict human risk.     

The sigma receptor as a ligand-regulated auxiliary potassium channel subunit

The sigma receptor is a novel protein that mediates the modulation of ion channels by psychotropic drugs through a unique transduction mechanism depending neither on G proteins nor protein phosphorylation. The present study investigated sigma receptor signal transduction by reconstituting responses in Xenopus oocytes. Sigma receptors modulated voltage-gated K+ channels (Kv1.4 or Kv1.5) in different ways in the presence and absence of ligands. Association between Kv1.4 channels and sigma receptors was demonstrated by coimmunoprecipitation. These results indicate a novel mechanism of signal transduction dependent on protein-protein interactions. Domain accessibility experiments suggested a structure for the sigma receptor with two cytoplasmic termini and two membrane-spanning segments. The ligand-independent effects on channels suggest that sigma receptors serve as auxiliary subunits to voltage-gated K+ channels with distinct functional interactions, depending on the presence or absence of ligand.     

Cell-specific fatty acylation of proteins in cultured cells of neuronal and glial origin

Distinct sets of cellular proteins were labeled with [³H]myristic and [³H]palmitic acids in primary (rat neurons and astroglia) and continuous (murine N1E-115 neuroblastoma and rat C6 glioma) cell cultures derived from the nervous system. Both soluble and membrane proteins were modified by myristate in a hydroxylamine-stable (amide) linkage, while palmitoylated proteins were esterlinked and almost exclusively membrane bound. Chain elongation of both labeled fatty acids prior to acylation was observed, but no protein amide-liked [³H]myristate originating from [³H]palmitate was detected. Fatty acylation profiles differed considerably among most of the cell lines, except for rat astroglial and glioma cells in which myristoylated proteins appeared to be almost identical based on SDS gel electrophoresis. An unidentified 47 kDa myristoylated protein was labeled to a significantly greater extent in astroglial than in glioma cells; the expression of this protein could be related to transformation or development in cells of glial origin.