Spring zooplankton distribution and production of the copepod Euterpina acutifrons in Marennes-Oléron Bay (France)

Short term variations of zooplankton populations were studied during an algal spring bloom in two characteristic areas of the Marennes-Oléron Bay (France). The sampling sites were chosen in the north of the bay, one close to the neritic zone, the other close to the estuarine zone. Five distinct zooplanktonic communities were observed: two typical neritic and estuarine assemblages, two eurytopic groups (linked to neritic or estuarine water masses) and an autochtonous community, widely distributed in the north of the bay. The copepod Euterpina acutifrons dominated the zooplankton community during this period of the year in terms of abundance (up to 83% of the zooplankton community). Its production differed between water masses: the highest production occurred at the estuarine station (3.48 ± 0.65 mg C m^–3 d^–1), where nauplii accounted for a large part of these high values. Its P/B ratio was similar at the two stations (0.196 and 0.209 d^–1).     

Synthesis and biological activities of peptidomimetic analogues of compound A71623, a potent and selective CCK-A receptor agonist

Summary The involvement of cholecystokinin receptors in the phenomenon of satiety has been the impetus for significant research efforts, leading to the design and synthesis of CCK-A selective agonists for the possible treatment of obesity. The Abbott laboratories have described a novel series of pseudotetrapeptides represented by compound A71623, a highly potent and selective peripheral receptor agonist, but possessing very poor bioavailability. Starting from the structural requirements of this series of compounds, a peptidomimetic study was investigated, especially focusing on the N-terminal part of A71623. Using standard coupling methods, introduction of unnatural aromatic amino acids bearing a 2-carboxyethyl side chain on their α-amino group, along with backbone length modulation, afforded selective analogues, presenting a highly modified peptidic backbone. From our two lead compounds, further optimization is under development, tending towards nonpeptidic structures.     

The hVps34‐SGK3 pathway alleviates sustained PI3K/Akt inhibition by stimulating mTORC1 and tumour growth

We explore mechanisms that enable cancer cells to tolerate PI3K or Akt inhibitors. Prolonged treatment of breast cancer cells with PI3K or Akt inhibitors leads to increased expression and activation of a kinase termed SGK3 that is related to Akt. Under these conditions, SGK3 is controlled by hVps34 that generates PtdIns(3)P, which binds to the PX domain of SGK3 promoting phosphorylation and activation by its upstream PDK1 activator. Furthermore, under conditions of prolonged PI3K/Akt pathway inhibition, SGK3 substitutes for Akt by phosphorylating TSC2 to activate mTORC1. We characterise 14h, a compound that inhibits both SGK3 activity and activation in vivo, and show that a combination of Akt and SGK inhibitors induced marked regression of BT‐474 breast cancer cell‐derived tumours in a xenograft model. Finally, we present the kinome‐wide analysis of mRNA expression dynamics induced by PI3K/Akt inhibition. Our findings highlight the importance of the hVps34‐SGK3 pathway and suggest it represents a mechanism to counteract inhibition of PI3K/Akt signalling. The data support the potential of targeting both Akt and SGK as a cancer therapeutic.     

Antigen-Specific Antibody Glycosylation Is Regulated via Vaccination

Antibody effector functions, such as antibody-dependent cellular cytotoxicity, complement deposition, and antibody-dependent phagocytosis, play a critical role in immunity against multiple pathogens, particularly in the absence of neutralizing activity. Two modifications to the IgG constant domain (Fc domain) regulate antibody functionality: changes in antibody subclass and changes in a single N-linked glycan located in the CH2 domain of the IgG Fc. Together, these modifications provide a specific set of instructions to the innate immune system to direct the elimination of antibody-bound antigens. While it is clear that subclass selection is actively regulated during the course of natural infection, it is unclear whether antibody glycosylation can be tuned, in a signal-specific or pathogen-specific manner. Here, we show that antibody glycosylation is determined in an antigen- and pathogen-specific manner during HIV infection. Moreover, while dramatic differences exist in bulk IgG glycosylation among individuals in distinct geographical locations, immunization is able to overcome these differences and elicit antigen-specific antibodies with similar antibody glycosylation patterns. Additionally, distinct vaccine regimens induced different antigen-specific IgG glycosylation profiles, suggesting that antibody glycosylation is not only programmable but can be manipulated via the delivery of distinct inflammatory signals during B cell priming. These data strongly suggest that the immune system naturally drives antibody glycosylation in an antigen-specific manner and highlights a promising means by which next-generation therapeutics and vaccines can harness the antiviral activity of the innate immune system via directed alterations in antibody glycosylation in vivo.       

Hematologic and hematochemical characteristics of the herring gull (Larus argentatus) and the buzzard (Buteo buteo)

Some hematological and hematochemical parameters in eight herring gulls (Larus argentatus) and in six buzzards (Buteo buteo) were checked. The buzzards were fed with ovine meat exclusively, while the herring gulls were fed with fish and ovine meat. Considerable differences between the two species were noted, particularly as far as the hematological and lipidic parameters are concerned. These differences are probably related to the aquatic life of the herring gull.     

Feedback effects of ovarian steroids on the hypothalamic-hypophyseal axis in the rabbit

The feedback effects of two ovarian steroids, estradiol-17 beta (E2) and 20 alpha-hydroxypregn-4-en-3-one (20 alpha OH), were examined in both intact (INT) and ovariectomized (OVEX) does. We measured steroid-induced alterations in endogenous gonadotropin-releasing hormone (GnRH) from sequential 10-min samples of hypothalamic perfusates, simultaneous changes in peripheral plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and the modification of pituitary responsiveness, i.e., increments in plasma LH (delta LH) and plasma FSH (delta FSH), after 50 ng, 250 ng, and 1 microgram of exogenous GnRH in individual does of 6 treatment groups. The groups were: INT does, OVEX does, OVEX does receiving either one (1 E2) or two (2 E2) E2-filled Silastic capsules, OVEX does receiving a 20 alpha OH-filled capsule (20 alpha OH), and OVEX does receiving both capsules of E2 and 20 alpha OH (1 E2 + 20 alpha OH). Ovariectomy enhanced the pulsatile release of hypothalamic GnRH and pituitary LH and FSH, and increased the LH response (delta LH) to exogenous GnRH (OVEX vs. INT, p less than 0.05). Replacement of E2 at the time of ovariectomy prevented the increased GnRH and gonadotropin secretion as well as the enhanced delta LH that were observed in untreated OVEX does. The release of hypothalamic GnRH in the 20 alpha OH group was lower (p less than 0.05) than that in the OVEX group and not different from that in the INT group. The release of pituitary LH and FSH and the delta LH in the 20 alpha OH group was not different from that in the OVEX group, but these parameters were greater (p less than 0.05) than those in the INT group. The hypothalamic GnRH pulse frequency in the 1 E2 + 20 alpha OH group was lower (p less than 0.05) than that in either the 1 E2 or the 20 alpha OH group, but the delta LH in the 1 E2 + 20 alpha OH group was not different from that in either the 1 E2 or the 20 alpha OH group. The highest dose (1 microgram) of exogenous GnRH stimulated a modest increase in FSH in the OVEX, 20 alpha OH, 1 E2 + 20 alpha OH, and 1 E2 groups; but a steroid effect on delta FSH among these 4 groups was not apparent.(ABSTRACT TRUNCATED AT 250 WORDS)     

A case of congenital non-spherocytic hemolytic anemia caused by enzyme deficiency in pyruvate kinase

About a familial observation of PK deficiency, the authors emphasize the important clinical and biochemical heterogeneity. Interest of isotopic explorations in the therapeutic decision of splenectomy.