Genetic enhancement of learning and memory in mice.

Hebb's rule (1949) states that learning and memory are based on modifications of synaptic strength among neurons that are simultaneously active. This implies that enhanced synaptic coincidence detection would lead to better learning and memory. If the NMDA (N-methyl-D-aspartate) receptor, a synaptic coincidence detector, acts as a graded switch for memory formation, enhanced signal detection by NMDA receptors should enhance learning and memory. Here we show that overexpression of NMDA receptor 2B (NR2B) in the forebrains of transgenic mice leads to enhanced activation of NMDA receptors, facilitating synaptic potentiation in response to stimulation at 10-100 Hz. These mice exhibit superior ability in learning and memory in various behavioural tasks, showing that NR2B is critical in gating the age-dependent threshold for plasticity and memory formation. NMDA-receptor-dependent modifications of synaptic efficacy, therefore, represent a unifying mechanism for associative learning and memory. Our results suggest that genetic enhancement of mental and cognitive attributes such as intelligence and memory in mammals is feasible.     

Electrical activity in early neuronal development

The construction of the brain during embryonic development was thought to be largely independent of its electrical activity. In this view, proliferation, migration and differentiation of neurons are driven entirely by genetic programs and activity is important only at later stages in refinement of connections. However, recent findings demonstrate that activity plays essential roles in early development of the nervous system. Activity has similar roles in the incorporation of newly born neurons in the adult nervous system, suggesting that there are general rules underlying activity-dependent development. The extensive involvement of activity makes it likely that it is required at all developmental stages as a necessary partner with genetic programs.     

早期成岩作用研究进展及发展方向

早期成岩作用作为一个重要的研究领域受到广泛关注。概括总结了早期成岩作用的主要特点、地质响应和研究思路，介绍了在元素的迁移转化、硫酸盐还原反应、数学模型及微生物成岩等理论领域和多金属结核及早期成岩成矿、环境沉积学、土壤性质评价与改良等应用领域的主要研究进展。早期成岩作用研究具有广阔的发展前景，未来可能在以下3方面快速取得突破：研究区域将进一步扩大，湖泊、三角洲及土壤中的相应研究将得以加强；多层的稳态或非稳态的一维、二维或三维的早期成岩数学模型将得以建立；其研究方法和理论成果将被广泛应用于环境沉积学及环境监测和治理等领域中。     

早期成岩作用研究进展及发展方向

早期成岩作用作为一个重要的研究领域受到广泛关注。概括总结了早期成岩作用的主要特点、地质响应和研究思路,介绍了在元素的迁移转化、硫酸盐还原反应、数学模型及微生物成岩等理论领域和多金属结核及早期成岩成矿、环境沉积学、土壤性质评价与改良等应用领域的主要研究进展。早期成岩作用研究具有广阔的发展前景,未来可能在以下3方面快速取得突破:研究区域将进一步扩大,湖泊、三角洲及土壤中的相应研究将得以加强;多层的稳态或非稳态的一维、二维或三维的早期成岩数学模型将得以建立;其研究方法和理论成果将被广泛应用于环境沉积学及环境监测和治理等领域中。     

A new eutriconodont mammal and evolutionary development in early mammals

Detachment of the three tiny middle ear bones from the reptilian mandible is an important innovation of modern mammals. Here we describe a Mesozoic eutriconodont nested within crown mammals that clearly illustrates this transition: the middle ear bones are connected to the mandible via an ossified Meckel's cartilage. The connected ear and jaw structure is similar to the embryonic pattern in modern monotremes (egg-laying mammals) and placental mammals, but is a paedomorphic feature retained in the adult, unlike in monotreme and placental adults. This suggests that reversal to (or retention of) this premammalian ancestral condition is correlated with different developmental timing (heterochrony) in eutriconodonts. This new eutriconodont adds to the evidence of homoplasy of vertebral characters in the thoraco-lumbar transition and unfused lumbar ribs among early mammals. This is similar to the effect of homeobox gene patterning of vertebrae in modern mammals, making it plausible to extrapolate the effects of Hox gene patterning to account for homoplastic evolution of vertebral characters in early mammals.     

Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine

The acquired immunodeficiency syndrome (AIDS)-causing lentiviruses human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) effectively evade host immunity and, once established, infections with these viruses are only rarely controlled by immunological mechanisms. However, the initial establishment of infection in the first few days after mucosal exposure, before viral dissemination and massive replication, may be more vulnerable to immune control. Here we report that SIV vaccines that include rhesus cytomegalovirus (RhCMV) vectors establish indefinitely persistent, high-frequency, SIV-specific effector memory T-cell (T(EM)) responses at potential sites of SIV replication in rhesus macaques and stringently control highly pathogenic SIV(MAC239) infection early after mucosal challenge. Thirteen of twenty-four rhesus macaques receiving either RhCMV vectors alone or RhCMV vectors followed by adenovirus 5 (Ad5) vectors (versus 0 of 9 DNA/Ad5-vaccinated rhesus macaques) manifested early complete control of SIV (undetectable plasma virus), and in twelve of these thirteen animals we observed long-term (≥1 year) protection. This was characterized by: occasional blips of plasma viraemia that ultimately waned; predominantly undetectable cell-associated viral load in blood and lymph node mononuclear cells; no depletion of effector-site CD4(+) memory T cells; no induction or boosting of SIV Env-specific antibodies; and induction and then loss of T-cell responses to an SIV protein (Vif) not included in the RhCMV vectors. Protection correlated with the magnitude of the peak SIV-specific CD8(+) T-cell responses in the vaccine phase, and occurred without anamnestic T-cell responses. Remarkably, long-term RhCMV vector-associated SIV control was insensitive to either CD8(+) or CD4(+) lymphocyte depletion and, at necropsy, cell-associated SIV was only occasionally measurable at the limit of detection with ultrasensitive assays, observations that indicate the possibility of eventual viral clearance. Thus, persistent vectors such as CMV and their associated T(EM) responses might significantly contribute to an efficacious HIV/AIDS vaccine.     

Biopolymers: shape memory in spider draglines

The ductility and strength of spider draglines means that they outperform the best synthetic fibres, but surprisingly little is known about the torsional properties of this remarkable filament. Unlike a mountain climber swinging from a rope, a spider suspended from its silk thread hardly ever twists. Here we show that a spider dragline has a torsional shape 'memory' in that it can reversibly and totally recover its initial form without any external stimulus; its observed relaxation dynamics indicate that these biological molecules have successively different torsional constants.