Science 21 March 2008:Vol. 319. no. 5870, pp. 1623 - 1624
NEUROSCIENCE:Detailed Differences
Brain imaging shows that, as in other animals, the human hippocampus has regions that help us keep our memories from becoming jumbled.

Science 21 March 2008:Vol. 319. no. 5870, pp. 1627 - 1628
NEUROSCIENCE:A Protoplasmic Kiss to Remember
During establishment of long-term memory, protein synthesis, regulated by neurotrophins, affects the morphology of synaptic structures.

Science 21 March 2008:Vol. 319. no. 5870, p. 1639
Preparing and Motivating Behavior Outside of Awareness
The mere activation of the idea of a behavioral act moves the human body without the person consciously deciding to take action. In an experiment, we showed that people subliminally primed with the concept of exertion were faster to squeeze a hand grip forcefully but expended more effort when the subliminal primes were directly accompanied by consciously visible positive stimuli. These findings demonstrate the human capacity to rely on mental processes in preparing and motivating behavior outside of awareness.

Science 21 March 2008: Vol. 319. no. 5870, pp. 1640 - 1642
Pattern Separation in the Human Hippocampal CA3 and Dentate Gyrus
Pattern separation, the process of transforming similar representations or memories into highly dissimilar, nonoverlapping representations, is a key component of many functions ascribed to the hippocampus. Computational models have stressed the role of the hippocampus and, in particular, the dentate gyrus and its projections into the CA3 subregion in pattern separation. We used high-resolution (1.5-millimeter isotropic voxels) functional magnetic resonance imaging to measure brain activity during incidental memory encoding. Although activity consistent with a bias toward pattern completion was observed in CA1, the subiculum, and the entorhinal and parahippocampal cortices, activity consistent with a strong bias toward pattern separation was observed in, and limited to, the CA3/dentate gyrus. These results provide compelling evidence of a key role of the human CA3/dentate gyrus in pattern separation.

Science 21 March 2008:Vol. 319. no. 5870, pp. 1665 - 1668
Activation of FOXO1 by Cdk1 in Cycling Cells and Postmitotic Neurons
Activation of cyclin-dependent kinase 1 (Cdk1) has been linked to cell death of postmitotic neurons in brain development and disease. We found that Cdk1 phosphorylated the transcription factor FOXO1 at Ser249 in vitro and in vivo. The phosphorylation of FOXO1 at Ser249 disrupted FOXO1 binding with 14-3-3 proteins and thereby promoted the nuclear accumulation of FOXO1 and stimulated FOXO1-dependent transcription, leading to cell death in neurons. In proliferating cells, Cdk1 induced FOXO1 Ser249 phosphorylation at the G2/M phase of the cell cycle, resulting in FOXO1-dependent expression of the mitotic regulator Polo-like kinase (Plk). These findings define a conserved signaling link between Cdk1 and FOXO1 that may have a key role in diverse biological processes, including the degeneration of postmitotic neurons.

Science 21 March 2008:Vol. 319. no. 5870, pp. 1668 - 1672
TDP-43 Mutations in Familial and Sporadic Amyotrophic Lateral Sclerosis
Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder characterized pathologically by ubiquitinated TAR DNA binding protein (TDP-43) inclusions. The function of TDP-43 in the nervous system is uncertain, and a mechanistic role in neurodegeneration remains speculative. We identified neighboring mutations in a highly conserved region of TARDBP in sporadic and familial ALS cases. TARDBPM337V segregated with disease within one kindred and a genome-wide scan confirmed that linkage was restricted to chromosome 1p36, which contains the TARDBP locus. Mutant forms of TDP-43 fragmented in vitro more readily than wild type and, in vivo, caused neural apoptosis and developmental delay in the chick embryo. Our evidence suggests a pathophysiological link between TDP-43 and ALS.

Science 21 March 2008:Vol. 319. no. 5870, pp. 1679 - 1683
Drosophila Egg-Laying Site Selection as a System to Study Simple Decision-Making Processes
The ability to select a better option from multiple acceptable ones is important for animals to optimize their resources. The mechanisms that underlie such decision-making processes are not well understood. We found that selection of egg-laying site in Drosophila melanogaster is a suitable system to probe the neural circuit that governs simple decision-making processes. First, Drosophila females pursue active probing of the environment before depositing each egg, apparently to evaluate site quality for every egg. Second, Drosophila females can either accept or reject a sucrose-containing medium, depending on the context. Last, communication of the "acceptability" of the sucrose-containing medium as an egg-laying option to the reproductive system depends on the function of a group of insulin-like peptide 7 (ILP7)–producing neurons. These findings suggest that selection of egg-laying site involves a simple decision-making process and provide an entry point toward a systematic dissection of this process.

Science 21 March 2008:Vol. 319. no. 5870, pp. 1683 - 1687
Protein Synthesis and Neurotrophin-Dependent Structural Plasticity of Single Dendritic Spines
Long-term potentiation (LTP) at glutamatergic synapses is considered to underlie learning and memory and is associated with the enlargement of dendritic spines. Because the consolidation of memory and LTP require protein synthesis, it is important to clarify how protein synthesis affects spine enlargement. In rat brain slices, the repetitive pairing of postsynaptic spikes and two-photon uncaging of glutamate at single spines (a spike-timing protocol) produced both immediate and gradual phases of spine enlargement in CA1 pyramidal neurons. The gradual enlargement was strongly dependent on protein synthesis and brain-derived neurotrophic factor (BDNF) action, often associated with spine twitching, and was induced specifically at the spines that were immediately enlarged by the synaptic stimulation. Thus, this spike-timing protocol is an efficient trigger for BDNF secretion and induces protein synthesis–dependent long-term enlargement at the level of single spines.

Science 21 March 2008:Vol. 319. no. 5870, pp. 1687 - 1688
Spending Money on Others Promotes Happiness
Although much research has examined the effect of income on happiness, we suggest that how people spend their money may be at least as important as how much money they earn. Specifically, we hypothesized that spending money on other people may have a more positive impact on happiness than spending money on oneself. Providing converging evidence for this hypothesis, we found that spending more of one's income on others predicted greater happiness both cross-sectionally (in a nationally representative survey study) and longitudinally (in a field study of windfall spending). Finally, participants who were randomly assigned to spend money on others experienced greater happiness than those assigned to spend money on themselves.

Nature 452, 294-295 (20 March 2008) | doi:10.1038/452294a; Published online 19 March 2007
Brain comes to light
To perceive seasons, animals compare changes in day length with the constant cycle of their inner circadian clock. At a molecular level, light signals trigger coordinated gene-expression events in the brain.
To survive, organisms must adapt to the constantly changing conditions of their surroundings. For example, most animals that live at temperate latitudes concentrate their reproductive efforts to times when environmental conditions such as temperature and food availability are optimal for the survival of their offspring.

Nature 452, 297-298 (20 March 2008) | doi:10.1038/452297a; Published online 19 March 2008
Punisher pays
The tendency of humans to punish perceived free-loaders, even at a cost to themselves, is an evolutionary puzzle: punishers perish, and those who benefit the most are those who have never punished at all.
Humans are champions of cooperation. Reciprocity — the idea that, if I help you this time, you'll help me next time1 — is a secret of our success.

Nature 452, 317-322 (20 March 2008) | doi:10.1038/nature06738; Received 22 July 2007; Accepted 25 January 2008
Thyrotrophin in the pars tuberalis triggers photoperiodic response
Molecular mechanisms regulating animal seasonal breeding in response to changing photoperiod are not well understood. Rapid induction of gene expression of thyroid-hormone-activating enzyme (type 2 deiodinase, DIO2) in the mediobasal hypothalamus (MBH) of the Japanese quail (Coturnix japonica) is the earliest event yet recorded in the photoperiodic signal transduction pathway. Here we show cascades of gene expression in the quail MBH associated with the initiation of photoinduced secretion of luteinizing hormone. We identified two waves of gene expression. The first was initiated about 14 h after dawn of the first long day and included increased thyrotrophin (TSH) β-subunit expression in the pars tuberalis; the second occurred approximately 4 h later and included increased expression of DIO2. Intracerebroventricular (ICV) administration of TSH to short-day quail stimulated gonadal growth and expression of DIO2 which was shown to be mediated through a TSH receptor–cyclic AMP (cAMP) signalling pathway. Increased TSH in the pars tuberalis therefore seems to trigger long-day photoinduced seasonal breeding.

Nature 452, 352-355 (20 March 2008) | doi:10.1038/nature06713; Received 16 June 2007;
Identifying natural images from human brain activity
A challenging goal in neuroscience is to be able to read out, or decode, mental content from brain activity. Recent functional magnetic resonance imaging (fMRI) studies have decoded orientation, position and object category from activity in visual cortex. However, these studies typically used relatively simple stimuli (for example, gratings) or images drawn from fixed categories (for example, faces, houses), and decoding was based on previous measurements of brain activity evoked by those same stimuli or categories. To overcome these limitations, here we develop a decoding method based on quantitative receptive-field models that characterize the relationship between visual stimuli and fMRI activity in early visual areas. These models describe the tuning of individual voxels for space, orientation and spatial frequency, and are estimated directly from responses evoked by natural images. We show that these receptive-field models make it possible to identify, from a large set of completely novel natural images, which specific image was seen by an observer. Identification is not a mere consequence of the retinotopic organization of visual areas; simpler receptive-field models that describe only spatial tuning yield much poorer identification performance. Our results suggest that it may soon be possible to reconstruct a picture of a person's visual experience from measurements of brain activity alone.

Nature 452, 370-374 (20 March 2008) | doi:10.1038/nature06780; Received 10 September 2007; Accepted 22 January 2008
SCFβ-TRCP controls oncogenic transformation and neural differentiation through REST degradation
The RE1-silencing transcription factor (REST, also known as NRSF) is a master repressor of neuronal gene expression and neuronal programmes in non-neuronal lineages. Recently, REST was identified as a human tumour suppressor in epithelial tissues, suggesting that its regulation may have important physiological and pathological consequences. However, the pathways controlling REST have yet to be elucidated. Here we show that REST is regulated by ubiquitin-mediated proteolysis, and use an RNA interference (RNAi) screen to identify a Skp1-Cul1-F-box protein complex containing the F-box protein β -TRCP (SCF- β TRCP) as an E3 ubiquitin ligase responsible for REST degradation. β -TRCP binds and ubiquitinates REST and controls its stability through a conserved phospho-degron. During neural differentiation, REST is degraded in a β-TRCP-dependent manner. β -TRCP is required for proper neural differentiation only in the presence of REST, indicating that β-TRCP facilitates this process through degradation of REST. Conversely, failure to degrade REST attenuates differentiation. Furthermore, we find that β -TRCP overexpression, which is common in human epithelial cancers, causes oncogenic transformation of human mammary epithelial cells and that this pathogenic function requires REST degradation. Thus, REST is a key target in β -TRCP-driven transformation and the β -TRCP–REST axis is a new regulatory pathway controlling neurogenesis.

BMJ  2008;336:581 (15 March), doi:10.1136/bmj.39518.354259.DB
Doctors hope consensus on brain death in China will boost transplants
Doctors, ethicists, and lawyers are to agree a definition for brain death for use by China’s medical community, which many doctors hope will boost organ transplants.
More than 200 delegates from the disciplines of neurosurgery, organ donation, and transplantation from China and elsewhere are expected to attend a conference at the end of April in Beijing hosted by the Organ Transplant Committee to develop a consensus on brain death. The conference is being administered by China’s Ministry of Health and chaired by Jiefu Huang, the vice minister for health.

BMJ  2008;336:594-597 (15 March), doi:10.1136/bmj.39465.544028.AE (published 21 February 2008)
Supplementation with antioxidants and folinic acid for children with Down’s syndrome: randomised controlled trial
Objectives To assess whether supplementation with antioxidants, folinic acid, or both improves the psychomotor and language development of children with Down’s syndrome.
Design Randomised controlled trial with two by two factorial design.
Setting Children living in the Midlands, Greater London, and the south west of England.
Participants 156 infants aged under 7 months with trisomy 21.
Intervention Daily oral supplementation with antioxidants (selenium 10 µg, zinc 5 mg, vitamin A 0.9 mg, vitamin E 100 mg, and vitamin C 50 mg), folinic acid (0.1 mg), antioxidants and folinic acid combined, or placebo.
Main outcome measures Griffiths developmental quotient and an adapted MacArthur communicative development inventory 18 months after starting supplementation; biochemical markers in blood and urine at age 12 months.
Results Children randomised to antioxidant supplements attained similar developmental outcomes to those without antioxidants (mean Griffiths developmental quotient 57.3 v 56.1; adjusted mean difference 1.2 points, 95% confidence interval –2.2 to 4.6). Comparison of children randomised to folinic acid supplements or no folinic acid also showed no significant differences in Griffiths developmental quotient (mean 57.6 v 55.9; adjusted mean difference 1.7, –1.7 to 5.1). No between group differences were seen in the mean numbers of words said or signed: for antioxidants versus none the ratio of means was 0.85 (95% confidence interval 0.6 to 1.2), and for folinic acid versus none it was 1.24 (0.87 to 1.77). No significant differences were found between any of the groups in the biochemical outcomes measured. Adjustment for potential confounders did not appreciably change the results.
Conclusions This study provides no evidence to support the use of antioxidant or folinic acid supplements in children with Down’s syndrome.

BMJ  2008;336:614-615 (15 March), doi:10.1136/bmj.39351.706586.AD
Change Page
Don’t add aspirin for associated stable vascular disease in a patient with atrial fibrillation receiving anticoagulation
Adding aspirin to warfarin does not seem to prevent stroke and vascular events in patients with atrial fibrillation and stable vascular disease
Bleeding risks are much higher in patients prescribed both warfarin and aspirin
We should stop prescribing aspirin plus warfarin to prevent stroke and vascular events in stable patients with atrial fibrillation who are receiving anticoagulation treatment.

JAMA. 2008;299(11):1252.
Intellectual Disability
A "microdeletion" on chromosome 15 is associated with a new syndrome characterized by intellectual disability, epilepsy, and facial and digital anomalies, according to an international team of scientists (Sharp AJ. Nat Genet. 10.1038/ng.93 [published online ahead of print February 17, 2008]).
The researchers scanned the genomes of 757 individuals with intellectual disability and/or other congenital anomalies, trawling for chromosomal deletions and duplications. They found a particular microdeletion in 2 unrelated individuals (and later in another 7 persons), an identical 1.5 million base-pair deletion that spanned 6 genes on chromosome 15. One of the missing genes, CHRNA7, encodes a protein involved in nerve cell signaling that previously had been proposed as a possible susceptibility factor for some forms of epilepsy.
The researchers estimated that the microdeletion accounts for about 0.3% of intellectual disability of unknown etiology and has an approximate population incidence of 1/40 000.

NEJM Volume 358:e13  March 20, 2008  Number 12
Spontaneous Otogenic Pneumocephalus
A healthy 54-year-old woman presented with progressive abnormal acoustic sensations, aphasia, and visual-field disturbances. She reported no head trauma or recent infection, such as otitis media. An initial cranial radiograph revealed air in the left temporal region without evidence of a fracture. A computed tomographic scan of the head showed a large amount of air in the left temporal lobe; the involved area was approximately
4 cm by 3 cm by 5 cm.