Effects of cerebral lateral,ventricular infusions of phloridzin on feeding and body weight in Gallus domesticus (L.)

Summary Contrary to earlier findings in rats, cerebral lateral ventricular infusions of 1×10^–3 M or 2×10^–3 M solutions of phloridzin at a rate of 2.5 l/min for 90 min had no significant stimulating effects on food intake and weight gain in hens and cocks. These different responses to intraventricular phloridzin might reflect a difference of sensitivity to the inhibitory action of phloridzin on glucose transport in cerebral cells or certain peculiarities of mechanisms controlling food intake in chickens.     

Mutations in lectin complement pathway genes COLEC11 and MASP1 cause 3MC syndrome

3MC syndrome has been proposed as a unifying term encompassing the overlapping Carnevale, Mingarelli, Malpuech and Michels syndromes. These rare autosomal recessive disorders exhibit a spectrum of developmental features, including characteristic facial dysmorphism, cleft lip and/or palate, craniosynostosis, learning disability and genital, limb and vesicorenal anomalies. Here we studied 11 families with 3MC syndrome and identified two mutated genes, COLEC11 and MASP1, both of which encode proteins in the lectin complement pathway (collectin kidney 1 (CL-K1) and MASP-1 and MASP-3, respectively). CL-K1 is highly expressed in embryonic murine craniofacial cartilage, heart, bronchi, kidney and vertebral bodies. Zebrafish morphants for either gene develop pigmentary defects and severe craniofacial abnormalities. Finally, we show that CL-K1 serves as a guidance cue for neural crest cell migration. Together, these findings demonstrate a role for complement pathway factors in fundamental developmental processes and in the etiology of 3MC syndrome.     

异常黑胆质成熟剂中各单味药对HL-60细胞增殖的抑制作用

异常黑胆质成熟剂是维吾尔医复方制剂,由甘草、红枣、破布木、牛舌草、铁线蕨、地锦草、小茴香、薰衣草、蜜蜂花和刺糖10味药组成,用于治疗由异常黑胆质所导致的肿瘤、糖尿病和心血管疾病等。研究了异常黑胆质成熟剂中各单味药(除刺糖外)对HL-60细胞增殖的抑制作用。HL-60细胞暴露于各单味药两种不同提取物(二氯甲烷和甲醇),于37℃、CO2体积分数为5%的恒温孵箱中培养后24、48、72h,用台盼蓝染色法检测细胞存活率。结果表明,各单味药的二氯甲烷提取物除小茴香外均显著降低HL-60癌细胞的存活率(P<0.05)。在甲醇提取物中,只有甘草和地锦草两味药的甲醇提取物可显著降低HL-60癌细胞的存活率(P<0.05)。与各单味药甲醇提取物相比,其二氯甲烷提取物均显著降低HL-60癌细胞的存活率(P<0.05)。结果显示,破布木、地锦草、铁线蕨、甘草、红枣、薰衣草、牛舌草和蜜蜂花8味药的二氯甲烷提取物和甘草、地锦草两味药的甲醇提取物均能抑制HL-60癌细胞的体外增殖。各单味药二氯甲烷提取物对HL-60细胞增殖的抑制作用均明显强于其相应的甲醇提取物。     

Crossing paths: interactions between the cell death machinery and growth factor survival signals

Cytokines and growth factors play a crucial role in the maintenance of haematopoietic homeostasis. They transduce signals that regulate the competing commitments of haematopoietic stem cells, quiescence or proliferation, retention of stem cell pluripotency or differentiation, and survival or demise. When the balance between these commitments and the requirements of the organisms is disturbed, particularly when it favours survival and proliferation, cancer may result. Cell death provoked by loss of growth factor signalling is regulated by the Bcl-2 family of apoptosis regulators, and thus survival messages transduced by growth factors must regulate the activity of these proteins. Many aspects of direct interactions between cytokine signalling and regulation of apoptosis remain elusive. In this review, we explore the mechanisms by which cytokines, in particular Interleukin-3 and granulocyte–macrophage colony-stimulating factor, promote cell survival and suppress apoptosis as models of how cytokine signalling and apoptotic pathways intersect.     

Reaction mechanism determines NMDA receptor response to repetitive stimulation

At central excitatory synapses, N-methyl-D-aspartate (NMDA) receptors, which have a high affinity for glutamate, produce a slowly rising synaptic current in response to a single transmitter pulse and an additional current after a second, closely timed stimulus. Here we show, by examining the kinetics of transmitter binding and channel gating in single-channel currents from recombinant NR1/NR2A receptors, that the synaptic response to trains of impulses is determined by the molecular reaction mechanism of the receptor. The rate constants estimated for the activation reaction predict that, after binding neurotransmitter, receptors hesitate for approximately 4 ms in a closed high-affinity conformation before they either proceed towards opening or release neurotransmitter, with about equal probabilities. Because only about half of the initially fully occupied receptors become active, repetitive stimulation elicits currents with distinct waveforms depending on pulse frequency. This high-affinity/low-efficiency activation mechanism might serve as a link between stimulation frequency and the directionality of the ensuing synaptic plasticity.     

Neurosphere-derived multipotent precursors promote neuroprotection by an immunomodulatory mechanism

In degenerative disorders of the central nervous system (CNS), transplantation of neural multipotent (stem) precursor cells (NPCs) is aimed at replacing damaged neural cells. Here we show that in CNS inflammation, NPCs are able to promote neuroprotection by maintaining undifferentiated features and exerting unexpected immune-like functions. In a mouse model of chronic CNS inflammation, systemically injected adult syngeneic NPCs use constitutively activated integrins and functional chemokine receptors to selectively enter the inflamed CNS. These undifferentiated cells survive repeated episodes of CNS inflammation by accumulating within perivascular areas where reactive astrocytes, inflamed endothelial cells and encephalitogenic T cells produce neurogenic and gliogenic regulators. In perivascular CNS areas, surviving adult NPCs induce apoptosis of blood-borne CNS-infiltrating encephalitogenic T cells, thus protecting against chronic neural tissue loss as well as disease-related disability. These results indicate that undifferentiated adult NPCs have relevant therapeutic potential in chronic inflammatory CNS disorders because they display immune-like functions that promote long-lasting neuroprotection.