Finding the center reliably: robust patterns of developmental gene expression

We investigate a mechanism for the robust identification of the center of a developing biological system. We assume the existence of two morphogen gradients, an activator emanating from the anterior, and a corepressor from the posterior. The corepressor inhibits the action of the activator in switching on target genes. We apply this system to Drosophila embryos, where we predict the existence of a hitherto undetected posterior corepressor. Using mathematical modeling, we show that a symmetric activator-corepressor model can quantitatively explain the precise midembryo expression boundary of the hunchback gene, and the scaling of this pattern with embryo size.     

Vessel length on SNAP MRA and TOF MRA is a potential imaging biomarker for brain blood flow

PurposeTo explore feasibility of using the vessel length on time-of-flight (TOF) or simultaneous non-contrast angiography and intraplaque hemorrhage (SNAP) MRA as an imaging biomarker for brain blood flow, by using arterial spin labeling (ASL) perfusion imaging and 3D phase contrast (PC) quantitative flow imaging as references.MethodsIn a population of thirty subjects with carotid atherosclerotic disease, the visible intracranial arteries on TOF and SNAP were semi-automatically traced and the total length of the distal segments was calculated with a dedicated software named iCafe. ASL blood flow was calculated automatically using the recommended hemodynamic model. PC blood flow was obtained by generating cross-sectional arterial images and semi-automatically drawing the lumen contours. Pearson correlation coefficients were used to assess the associations between the different whole-brain or hemispheric blood flow measurements.ResultsUnder the imaging protocol used in this study, TOF vessel length was larger than SNAP vessel length (P < 0.001). Both whole-brain TOF and SNAP vessel length showed a correlation with whole brain ASL and 3D PC blood flow measurements, and the correlation coefficients were higher for SNAP vessel length (TOF vs ASL: R = 0.554, P = 0.002; SNAP vs ASL: R = 0.711, P < 0.001; TOF vs 3D PC: R = 0.358, P = 0.052; SNAP vs 3D PC: R = 0.425, P = 0.019). Similar correlation results were observed for the hemispheric measurements. Hemispheric asymmetry index of SNAP vessel length also showed a significant correlation with hemispheric asymmetry index of ASL cerebral blood flow (R = 0.770, P < 0.001).ConclusionThe results suggest that length of the visible intracranial arteries on TOF or SNAP MRA can serve as a potential imaging marker for brain blood flow.     

Regional variation in rat brain proton relaxation times and water content

Relaxation times (T1 and T2) and water content are measured in frontal cortex, amygdaloid cortex, hippocampus, mid-brain and cerebellum of rat brain. Differences are found in relaxation times, between areas containing a mixture of grey and white matter, and grey matter only. Differences were also found between certain grey matter areas. Relaxation times correlated with water content.     

Fragile X astrocytes induce developmental delays in dendrite maturation and synaptic protein expression

Background  

Fragile X syndrome is the most common inherited form of mental impairment characterized by cognitive impairment, attention deficit and autistic behaviours. The mouse model of Fragile X is used to study the underlying neurobiology associated with behavioral deficiencies. The effect of Fragile X glial cells on the development of neurons has not been studied. We used a co-culture technique in combination with morphometrics on immunostained neurons to investigate the role of astrocytes in the development delays associated with hippocampal neuron development.     

Regional and modular expression of morphogenetic factors in the demosponge Lubomirskia baicalensis

Some sponges [phylum Porifera], e.g. the demosponges Lubomirskia baicalensis or Axinella polypoides, show an arborescent growth form. In the freshwater sponge L. baicalensis this morphotype is seen mostly in depths below 4m while in more shallow regions it grows as a crust. The different growth forms are determined in nature very likely by water current and/or light. The branches of this species are composed of modules, arranged along the apical-basal axis. The modules are delimited by a precise architecture of the spicule bundles; longitudinal bundles originate from the apex of the earlier module, while at the basis of each module these bundles are cross-linked by traverse bundles under formation of annuli. Genes encoding putative morphogenetic factors, myotrophin and epidermal growth factor (EGF)-like molecules, and one gene of an antagonist for the Wnt signaling pathway, the soluble frizzled molecule, have been identified and characterized. Their expression levels as well as those of silicatein, one major spicule-forming molecule, have been studied in the crusts and the modules. The data revealed that at the apices of each module higher level of expression of myotrophin and EGF can be detected, while the base of each module is characterized by a high steady-state expression level of soluble frizzled molecule. These results suggest that module formation in L. baicalensis is controlled by a tuned interaction of agonistic (e.g., myotrophin and EGF) as well as antagonistic morphogenetic factors (e.g., soluble frizzled molecule).     

Expression patterns of Neil3 during embryonic brain development and neoplasia

Background  

The base excision repair pathway is responsible for repairing small DNA base lesions caused by endogenous and exogenous damaging agents. Repair is initiated by DNA glycosylases that recognize and remove the lesions. NEIL3 is one of 11 mammalian DNA glycosylases identified to date and it was discovered on the basis of sequence homology to the E. coli Fpg and Nei glycosylases. Difficulties in purifying the protein have limited its biochemical characterization and in contrast to the other glycosylases, its function remains unclear.     

Regional variations and the effects of age and gender on glutamate concentrations in the human brain

Proton magnetic resonance spectroscopy was performed at 3 T using the echo time-averaged point-resolved spectroscopy method to determine the effects of age, gender and brain region on glutamate (Glu) concentrations in the healthy human brain. Thirty healthy men and 20 healthy women aged between 21 and 71 years were studied. Significant regional variations of Glu concentrations were observed. Glu concentration in the gray matter (GM) was approximately 25% higher than that in the white matter. Significant age-dependent decreases in Glu concentrations were observed in the basal ganglia (r=-0.75, P<.001) and parietal GM (r=-0.66, P<.001) of men but not those of women. Our findings demonstrate regional variations of Glu concentrations and suggest that the male brain may be more vulnerable to aging than the female brain. Our results also highlight the importance of brain region, age and gender matching in clinical studies.     

Alternative splicing variations in mouse CAPS2: differential expression and functional properties of splicing variants

Background  

Ca²⁺-dependent activator protein 2 (CAPS2/CADPS2) is a secretory vesicle-associated protein involved in the release of neurotrophin. We recently reported that an aberrant, alternatively spliced CAPS2 mRNA that lacks exon 3 (CAPS2Δexon3) is detected in some patients with autism. Splicing variations in mouse CAPS2 and their expression and functions remain unclear.     

(1)H-MRS metabolic patterns for distinguishing between meningiomas and other brain tumors

Yet meningiomas have characteristic neuroimaging features, some other lesions are still confusing with meningiomas. The aim of this study was trying to find the typical (1)H-MRS metabolic factors of histologic subtyped meningiomas, schwannomas, metastases, and other brain tumors for differential diagnosis among them. (1)H-MRS using STEAM (TE/30 ms, TR/2 sec) and PRESS (TE/288 ms, TR/2 sec) sequences were performed on 44 untreated brain tumors. Obtained metabolic patterns from the typical spectra of meningioma, schwannoma, metastasis were compared with each other or other brain tumors to evaluate the usefulness for diagnosis between them. Alanine(Ala) was observed in 15 cases of the 19 meningiomas with a little variation to three histologic subtypes, while minimal lipids were observed in every 19 meningiomas. Elevated glutamate/glutamine(Glx) was detected in 12 cases of the meniningiomas. Increased myo-inositol(mI) was detected in 11 cases of the 13 schwannomas. Dominant lipids signals as well as long-T2 lipids were detected in every metastasis in conjunction with elevated choline (Cho). Enhanced Glx was observed in 4 cases of the 8 metastases without correlation of primary tumor site or types. Hemangiopericytoma showed different spectral patterns from typical meningiomas: only dominant Cho, minimal lipids and absence of Ala or Glx signals. These metabolic patterns in typical tumors may provide a basis for differential diagnosis (average value of chi(2) = 23.33, p < 0.01) between meningiomas and schwannomas as well as metastases. However proton spectral distinction among the different histologic subtypes of meningiomas was not definite.     

Reelin expression during embryonic development of the pig brain

Background  

Reelin is an extracellular glycoprotein of crucial importance in the developmental organisation of neurons in the mammalian cerebral cortex and other laminated brain regions. The pig possesses a gyrencephalic brain that bears resemblance to the human brain. In order to establish an animal model for neuronal migration disorders in the pig, we have studied the expression pattern and structure of Reelin during pig brain development.     

Sex-dependent gene expression in early brain development of chicken embryos

Background  

Differentiation of the brain during development leads to sexually dimorphic adult reproductive behavior and other neural sex dimorphisms. Genetic mechanisms independent of steroid hormones produced by the gonads have recently been suggested to partly explain these dimorphisms.     

Molecular characterization and temporal expression profiling of presenilins in the developing porcine brain

Background  

The transmembrane presenilin (PSEN) proteins, PSEN1 and PSEN2, have been proposed to be the catalytic components of the γ-secretase protein complex, which is an intramembranous multimeric protease involved in development, cell regulatory processes, and neurodegeneration in Alzheimer's disease. Here we describe the sequencing, chromosomal mapping, and polymorphism analysis of PSEN1 and PSEN2 in the domestic pig (Sus scrofa domesticus).     

On single-crystal neutron-diffraction in DACs: quantitative structure refinement of light elements on SNAP and TOPAZ

ABSTRACT

Quantitative single crystal neutron-diffraction in diamond anvil cells has so far been limited by the neutron flux available at the various neutron sources. As a result, highly precise measurements of the exact position of light elements have not been possible preventing, for example, structural studies of hydrogen and hydrogen bonds under pressure. Here we report experiments carried out on SNAP at the Spallation Neutron Source (ORNL, TN, USA) to explore the possibility and current limits of such studies. Furthermore, we benchmarked the obtained data quality with reference experiments carried out on TOPAZ, a dedicated single-crystal instrument.

We show that measuring single-crystal diffraction intensities on SNAP is possible to such a precision that we are able to resolve the hydrogen bonds in potassium dideuterium phosphate (DKDP) as well as in ice VI.     

Spins and parities of hole states in25Na and25Mg

Angular distributions of differential cross sections and vector analyzing powers were measured forl=0, 1 and 2 transitions induced by the \(^{26} Mg\left( {\overrightarrow d ,\tau } \right)^{25} Na\) reaction at 52 MeV. The following spins and parities of final states in²⁵Na were deduced:J ^π =1/2⁺ (1.069 MeV), 3/2⁺ (2.202 MeV), 5/2⁺ (2.914 MeV), 1/2^? (3.995 MeV) and 3/2^? (5.190, 5.690, 6.549 and 7.603 MeV). The DWBA analysis of proton and neutron pick-up spectra obtained from a parallel measurement of the²⁶Mg(d, τ)²⁵Na and²⁶Mg(d, t)²⁵Mg reactions allows the identification ofT=3/2 analog states in²⁵Mg. Interpretation in terms of the Nilsson model of energies and spectroscopic factors of the first 1/2^? and 3/2^? hole states observed in proton pick-up reactions from even 1d _5/2- shell nuclei indicates a close correspondence of the final state deformations with those of the first excited 2⁺ states in the target nuclei.     

Semantic,syntactic, and phonological processing of written words in adult developmental dyslexic readers: an event-related brain potential study

Background

The present study used event-related brain potentials to investigate semantic, phonological and syntactic processes in adult German dyslexic and normal readers in a word reading task. Pairs of German words were presented one word at a time. Subjects had to perform a semantic judgment task (house – window; are they semantically related?), a rhyme judgment task (house – mouse; do they rhyme?) and a gender judgment task (das – Haus [the – house]; is the gender correct? [in German, house has a neutral gender: das Haus]).

Results

Normal readers responded faster compared to dyslexic readers in all three tasks. Onset latencies of the N400 component were delayed in dyslexic readers in the rhyme judgment and in the gender judgment task, but not in the semantic judgment task. N400 and the anterior negativity peak amplitudes did not differ between the two groups. However, the N400 persisted longer in the dyslexic group in the rhyme judgment and in the semantic judgment tasks.

Conclusion

These findings indicate that dyslexics are phonologically impaired (delayed N400 in the rhyme judgment task) but that they also have difficulties in other, non-phonological aspects of reading (longer response times, longer persistence of the N400). Specifically, semantic and syntactic integration seem to require more effort for dyslexic readers and take longer irrespective of the reading task that has to be performed.

     

The role of the t-SNARE SNAP-25 in action potential-dependent calcium signaling and expression in GABAergic and glutamatergic neurons

Background  

The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, comprised of SNAP-25, syntaxin 1A, and VAMP-2, has been shown to be responsible for action potential (AP)-dependent, calcium-triggered release of several neurotransmitters. However, this basic fusogenic protein complex may be further specialized to suit the requirements for different neurotransmitter systems, as exemplified by neurons and neuroendocrine cells. In this study, we investigate the effects of SNAP-25 ablation on spontaneous neuronal activity and the expression of functionally distinct isoforms of this t-SNARE in GABAergic and glutamatergic neurons of the adult brain.     

Gamma-ray spectroscopy of 25 57 Mn32 and 25 58 Mn33

The decays of ₂₅⁵⁷Mn₃₂ and ₂₅⁵⁸Mn₃₃ have been studied with the 8π Spectrometer following the reaction ⁴⁸Ca(¹³C,pxn)^{60 − x} Mn at a beam energy of 40 MeV. The level schemes of these two nuclei have been extended, and the multipolarities of the observed transitions have been determined.     

Relaxo-volumetric multispectral quantitative magnetic resonance imaging of the brain over the human lifespan: global and regional aging patterns

The objective of this study was to determine the T1, T2 and secular-T2 relaxo-volumetric brain aging patterns using multispectral quantitative magnetic resonance imaging, both globally and regionally, and covering an age range approaching the full human lifespan. Fifty-one subjects (28 males, 23 females; age range: 0.5–87 years) were studied consisting of 18 healthy volunteers and 33 patients. Patients were selected after carefully reviewing their radiology reports to have either normal-by-MRI findings (25 patient subjects) or small focal pathology less than 6 mm in size (eight patient subjects). All subjects were MR imaged at 1.5 T with the mixed turbo spin echo pulse sequence. The soft tissues inside the cranial vault, termed intracranial matter (ICM), were segmented using a dual-clustering segmentation algorithm. ICM segments were further divided into six subsegments: bilateral anterior cerebral, posterior cerebral and cerebellar subsegments. T1, T2 and secular-T2 relaxation time histograms of all segments were generated and modeled with Gaussian functions. For each segment, the volumes of white matter, gray matter and cerebrospinal fluid were calculated from the T1 histograms. The age-related tendencies of three quantitative MRI parameters (T1, T2 and secular-T2) and the fractional tissue volumes showed four distinct periods of life, specifically a maturation period (0–2 years), a development period (2–20 years), an adulthood period (20–60 years) and a senescence period (60 years and older). For all ages, the anterior cerebral subsegment exhibited consistently longer gray matter T1s and shorter white matter T1s than the posterior cerebral and cerebellar subsegments. Volumetric age-related changes of the cerebellar subsegment were more gradual than in the cerebral subsegments. This study shows that relaxometric and volumetric age-related changes are synchronized and define the same four periods of brain evolution both globally and regionally.     

Regional distribution of manganese found in the brain after injection of a single dose of manganese-based contrast agents

Manganese (Mn) complexes are unstable and dissociate in vivo. Because of the release of this metal, there exists some concern about the potential long-term neurotoxicity associated with the use of Mn-based contrast agents. This latter problem arises because manganese is known to accumulate in specific regions of the brain of people intoxicated by this metal. It was previously demonstrated that Mn can accumulate in the mice brain after administration of 5 μmol/kg of MnCl₂, Mn-diethylenetriaminepentaacetate (Mn-DTPA), or Mn-dipyridoxal diphosphate (Mn-DPDP). In order to better characterize the behavior of Mn complexes after administration, this study assesses the regional distribution of Mn in the brain after i.v. injection of a single dose of MnCl₂ or Mn-DTPA. Male Wistar rats received an i.v. injection of 5 μmol/kg of ⁵⁴Mn as MnCl₂ or Mn-DTPA. The rats were killed at one and two weeks post exposure. The distribution of the radioactivity in the slices was monitored by autoradiography. For both MnCl₂ or Mn-DTPA, we observed that the radioactivity was dispersed in the entire brain, but the radioactivity was higher in several regions. No difference was observed between MnCl₂ or Mn-DTPA in the regional distribution of Mn, and no difference was observed between the two times of exposure (1 week or 2 weeks). The uptake of Mn was minimal in corpus callosum. Maximal Mn concentration was observed in the hippocampal region, thalamus, colliculi, amygdala, olfactory nuclei, and cerebellum.     

S-25与地NewS-25光阴极光谱响应特性的研究

本文研究了S-25与NewS-25光阴极的光谱响应特性.在850～1000nm范围光谱响应的提高主要归因于阴极层较厚,具有较大的阴极结构参量和截止波长.这既体现了NewS-25光阴极的优越性,也代这表了多碱阴极的发展方向.