Immunoregulatory T-cell defects in B-cell chronic lymphocytic leukemia: cause or consequence of the disease? The contributory role of decreased availability of interleukin 2 (IL-2)

Several phenotypic and functional defects have been described within the residual T-lymphocyte population of patients with B-cell chronic lymphocytic leukemia (B-CLL), particularly in those in the more advanced stages of the disease. In this study, we review these abnormalities and discuss their possible effects on the course of the illness. Particular emphasis is devoted to the role of interleukin 2 (IL-2) in B-CLL. Evidence is provided that the IL-2 released by B-CLL T-lymphocytes may be utilized by the neoplastic B-cell clone that expresses the IL-2 receptor and that decreased availability of IL-2 may play a contributory role in some of the T-cell defects encountered in B-CLL.     

Mutants blocked in penicillin biosynthesis show a deletion of the entire penicillin gene cluster at a specific site within a conserved hexanucleotide sequence

The organization of the genes of the penicillin cluster has been studied in three different mutants of P. chrysogenum impaired in penicillin biosynthesis. The three blocked mutants (derived from the parental strain P. chrysogenum Bb-1) lacked the genes pcbAB, pcbC and penDE of the penicillin biosynthetic pathway and were unable to form isopenicillin N synthase and isopenicillin N acyltransferase. All strains were identified as P. chrysogenum derivatives by fingerprinting analysis with (GTG)_n as a probe. The borders of the deleted region were cloned and sequenced, showing the same junction point in the three mutants. The deleted DNA region was found to be identical to that described in P. chrysogenum npe10. The frequent deletion of the pen gene cluster at this point may indicate that this cluster is located in an unstable genetic region, flanked by hot spots of recombination, that is easily lost by mutagen-induced recombination.     

An increase in nitric oxide produced by rat peritoneal neutrophils is not involved in cell apoptosis

Polymorphonuclear neutrophils (PMN) obtained from carrageenin-stimulated peritoneal cavities of rats, but not blood PMN, spontaneously produced nitric oxide (NO) when incubated in vitro. Incubation of the cells with the NO synthase inhibitors, L-imino-ethyl-L-ornithine (L-NIO) or N(G)-monomethyl-L-arginine (L-NMMA), inhibited NO production. This inhibition could be reversed by L-arginine. Incubation of PMN with lipopolysaccharide (LPS) failed to enhance NO production. Pretreatment of the rats with dexamethasone (DEXA) prior to carrageenin injection or incubation of PMN with the glucocorticoid in vitro partially inhibited the spontaneous release of NO. On the other hand, when PMN obtained from DEXA pretreated rats were incubated in vitro with DEXA, NO synthase activity and hence NO generation were almost abolished. A similar inhibition was also observed following the addition of L-NIO or cycloheximide to cultures of carrageenin-elicited PMN. The NO production by PMN did not appear to be related to cell viability or apoptosis. Indeed, neither the blockade of NO generation by L-NIO nor the incubation of the neutrophils with a NO donor, S-nitroso-acetylpenicillamine (SNAP) modified the pattern of LDH release or DNA fragmentation. In summary, it appears that PMN migration triggers a continuous NO synthesis, and that NO produced by these cells is not related to their apoptosis.     

若尔盖人-狼冲突现状与管理研究

大中型食肉动物肇事事件导致人类与野生动物关系恶化,给生物多样性保护工作带来巨大的挑战。若尔盖湿地是我国三大湿地之一,湿地、草原分布广泛,生物多样性丰富,畜牧业发达,但近年来狼(Canis lupus)捕杀牲畜的肇事事件时有发生。为了解若尔盖野生狼肇事件的空间分布以及牧民对人-狼冲突管理的看法,本研究于2022年对若尔盖县13个乡镇83个行政村进行走访调查。结果表明：(1)多数受访者(66.0%)认为在过去5年内,若尔盖县野生狼数量有所增加;(2)狼肇事事件具有明显的空间分异性,最严重的是包座乡。包座乡临近山区,该区域牧场面积广阔、牧民饲养牲畜数量多等原因导致该镇发生狼肇事事件较多;(3)对于狼肇事,绝大多数牧民(85.0%)更希望采取经济补偿或者驱赶措施,只有少数牧民(9.4%)希望采取捕杀的措施;(4)影响牧民对狼肇事管理措施的偏好因子中,受教育程度、年龄、民族以及被杀牲畜数量有显著影响。建议加强狼种群监测管理,采取措施减少狼捕杀牲畜,优化补偿机制,缓解当地牧民与狼之间的矛盾。本研究为当前若尔盖县野生动物保护和管理决策提供了依据,对其他地区大型食肉动物与当地居民冲突管理具有借鉴意义。     

Synthesis and structures of mono and binuclear nickel(II) thiolate complexes of a dicompartmental pseudo-macrocycle with N(imine)2S2 and N(oxime)2S2 metal-binding sites

The reaction of [Ni(pftp)] [pftp = N,N-propane-1,3-diyl-(6-formyl-4-methyliminatothiophenolato)] with hydroxylamine hydrochloride in the presence potassium acetate in MeOH resulted in the formation of the complex [Ni(LH₂)] [L = N,N-propane-1,3-diyl-(4-methyl-2-methyliminato-6-methyloxime-thiophenolato)] in good yield. A single crystal X-ray diffraction structural determination showed a mononuclear nickel(II) complex with the new acyclic ligand LH₂ that had been functionalised with two oxime groups containing an empty N(oxime)₂S₂ pocket to which another metal ion could be added. A further reaction of [Ni(LH₂)] with NiCl₂·6H₂O, triethylamine and ammonium hexafluorophosphate in MeOH gave a dark red product that yielded red crystals of [Ni₂(LH)]PF₆·DMF via slow recrystallisation from a DMF/PrⁱOH solvent mixture. A single crystal X-ray diffraction study of these crystals confirmed the presence of a dinuclear nickel(II) complex linked by a dithiolato-bridge. Both nickel(II) ions exhibited square-planar geometry where the metal centres are coordinated in two distinct cis-S₂N(imine)₂ and cis-S₂N(oxime)₂ binding sites provided by the new dicompartmental oxime/thiolate-containing ligand LH.     

Angiogenesis and lipoxins

Angiogenesis, the growth of new capillaries from pre-existing ones, occurs through dynamic functions of the endothelial cells (EC), including migration, proliferation and maturation, which are essential to achieve an organized formation of the vessel sprout. Aspirin-triggered lipoxins (ATL), the 15R enantiomeric counterparts of native lipoxins, are endogenous lipid mediators generated within the vascular lumen during multicellular responses, which display potent and well-described immunomodulatory actions. Here we present some of the findings regarding the inhibition of EC responses in vitro and in vivo by these novel compounds and the modulation of fundamental steps of the angiogenic process, identifying previously unappreciated vascular actions of locally generated ATL and their longer acting synthetic analogs.     

Evolutionary conservation of plant gibberellin signalling pathway components

Background:  

Gibberellins (GA) are plant hormones that can regulate germination, elongation growth, and sex determination. They ubiquitously occur in seed plants. The discovery of gibberellin receptors, together with advances in understanding the function of key components of GA signalling in Arabidopsis and rice, reveal a fairly short GA signal transduction route. The pathway essentially consists of GID1 gibberellin receptors that interact with F-box proteins, which in turn regulate degradation of downstream DELLA proteins, suppressors of GA-controlled responses.