The contribution of intermolecular spin interactions to the London dispersion forces between chiral molecules.

Dispersion interactions are one of the components of van der Waals (vdW) forces that play a key role in the understanding of intermolecular interactions in many physical, chemical, and biological processes. The theory of dispersion forces was developed by London in the early years of quantum mechanics. However, it was only in the 1960s that it was recognized that for molecules lacking an inversion center, such as chiral and helical molecules, there are chirality-sensitive corrections to the dispersion forces proportional to the rotatory power known from the theory of circular dichroism and with the same distance scaling law R-6 as the London energy. The discovery of the chirality-induced spin selectivity effect in recent years has led to an additional twist in the study of chiral molecular systems, showing a close relation between spin and molecular geometry. Motivated by it, we propose in this investigation to describe the mutual induction of charge and spin-density fluctuations in a pair A-B of chiral molecules by a simple physical model. The model assumes that the same fluctuating electric fields responsible for vdW forces can induce a magnetic response via a Rashba-like term so that a spin-orbit field acting on molecule B is generated by the electric field arising from charge density fluctuations in molecule A (and vice versa). Within a second-order perturbative approach, these contributions manifest as an effective intermolecular exchange interaction. Although expected to be weaker than the standard London forces, these interactions display the same R-6 distance scaling.

[Evaluation of mitral regurgitation : How much quantification do we need?] / Diagnostik der Mitralinsuffizienz : Wie viel und welche Quantifizierung brauchen wir?

Severe mitral regurgitation (MR) is associated with increased morbidity and mortality. Thus, the correct evaluation of the underlying etiology, pathomechanism and severity is crucial for optimal treatment. Echocardiography is the predominant diagnostic modality in the clinical routine as it enables grading of mitral regurgitation, which can frequently be achieved by readily available qualitative parameters. Additionally, echocardiography provides several methods to quantify the hemodynamic significance of MR. The effective regurgitation orifice area (EROA) is the quantitative parameter best correlated with clinical events. American and European imaging guidelines both recommend the use of quantitative parameters even though they disagree on the cut-off values for secondary MR. The evaluation of MR should always include an assessment of the adjacent heart chambers in order to be able to assess the impact of volume overload on size and function of the left ventricle and left atrium. The final interpretation of the quantitative parameters requires knowledge of left ventricular volume and ejection fraction. Newer 3D-echocardiographic approaches to quantify MR are less dependent on mathematical assumptions and have shown convincing results in several studies but still lack sufficient clinical validation. As an alternative to echocardiography, for specific indications cardiac magnetic resonance imaging (MRI) has proven to be a systematic and observer-independent method for quantification of MR.

[The reverse shoulder arthroplasty Delta Xtend : Mid-term results]. / Die inverse Schulterendoprothese Delta Xtend : Mittelfristige Ergebnisse.

BACKGROUND: Reverse shoulder arthroplasty (RSA) has become a frequently used and established treatment for patients with cuff tear arthropathy, increasingly also for patients with fracture sequelae (FS), failed rotator cuff reconstruction and omarthrosis with cuff insufficiency. Since 2007 new generation prostheses, for example Delta Xtend (Depuy, Warsaw, USA), have been used, but few mid-term results have been published. OBJECTIVES: The aim of this study is to report on the outcome after RSA after a mean follow-up of 68 months (range 63-75), to verify the already published, encouraging early results and to learn about the function and pain situation after RSA in the mid-term period. METHODS: 60 patients underwent RSA with the Depuy Delta Xtend prosthesis in the years 2007 and 2008, performed by the senior author of this study. 39 of these patients were available for follow up and were asked to complete a questionnaire (msCS, modified subjective Constant Score). In addition, 28 patients agreed to a clinical examination. With these patients, in addition, the constant score, age and gender-adjusted constant score and range of motion were evaluated. RESULTS: The mean msCS of preoperative 39.15 points (range 12-69) improved to 71.74 points (range 44-100) after 5 years. The mean CS at 5 years was 65.79 points (range 21-93) and the mean age and gender-adjusted constant score was 92%. The mean active anterior elevation was 139° (range 70-180°), the mean abduction was 135° (range 50-170°) and the mean active external rotation was 17° (range -20-40°). CONCLUSION: This study confirms good early results after RSA after more than 5 years. We see very good outcomes in patients with CTA and omarthrosis, whilst the rate of complication is low.

[Nailfold capillaroscopy]. / Nagelfalzkapillarmikroskopie.

Capillaroscopy is performed to evaluate the morphology, frequency and blood flow of nailfold capillaries as well as relevant extracapillary changes in rheumatic conditions. The main indication is the differentiation between primary and secondary Raynaud's phenomenon. Various rheumatic conditions show different and partially typical pathognomonic alterations of the microcirculation or capillary patterns. This simple, noninvasive, inexpensive and effective technique is well suited for early diagnosis, especially of connective tissue diseases. The specific significance is highest for systemic sclerosis which is the most frequently evaluated entity. The corresponding microscopic alterations allow stage-adapted conclusions concerning the acuity of inflammation to be formed. That is not the only reason why capillaroscopy represents an important tool in follow-up controls and together with other techniques, such as flow measurement by laser Doppler, further conclusions can be drawn.

Prospective ECG-gated High-Pitch Photon-Counting CT Angiography: Evaluation of measurement accuracy for aortic annulus sizing in TAVR planning.

PURPOSE: In planning transcatheter aortic valve replacement (TAVR), retrospective cardiac spiral-CT is recommended to measure aortic annulus with subsequent CT-angiography (CTA) to evaluate access routes. Photon-counting detector (PCD)-CT enables to assess the aortic annulus in desired cardiac phases, using prospective ECG-gated high-pitch CTA. The aim of this study was to evaluate the measurement accuracy of aortic annulus using prospective ECG-gated high-pitch CTA against retrospective spiral-CT reference. METHOD: Thirty patients underwent cardiac spiral-CT and prospective ECG-gated (30% R-R on aortic valve level) high-pitch CTA. Using propensity score matching, another 30 patients were identified whose CTA was performed using high-pitch mode without ECG-synchronization. Two investigators measured annular diameter, perimeter, and area on cardiac spiral-CT and high-pitch CTA. RESULTS: The aortic valve was imaged in systole in 90 % of prospective ECG-gated CTA cases but only 50 % of non-ECG-gated CTA cases (p = 0.002). There was a strong correlation (r ≥ 0.94) without significant differences (p ≥ 0.09) between cardiac spiral-CT and prospective ECG-gated high-pitch CTA for all annulus measurements. In contrast, significant differences were found in annular short-axis diameter and area between cardiac spiral-CT and non-ECG-gated high-pitch CTA (p ≤ 0.03). Furthermore, prospective ECG-gated high-pitch CTA showed significantly reduced radiation exposure compared with cardiac spiral-CT (CTDI 4.52 vs. 24.10 mGy; p < 0.001). CONCLUSION: PCD-CT-based prospective ECG-gated high-pitch scans with targeted systolic acquisition at the level of the aortic valve can simultaneously visualize TAVR access routes and accurately measure systolic annulus size. This approach could aid in optimizing protocols to achieve lower radiation doses in the growing population of younger, low-risk TAVR patients.

Convergent functional genomics of schizophrenia: from comprehensive understanding to genetic risk prediction.

We have used a translational convergent functional genomics (CFG) approach to identify and prioritize genes involved in schizophrenia, by gene-level integration of genome-wide association study data with other genetic and gene expression studies in humans and animal models. Using this polyevidence scoring and pathway analyses, we identify top genes (DISC1, TCF4, MBP, MOBP, NCAM1, NRCAM, NDUFV2, RAB18, as well as ADCYAP1, BDNF, CNR1, COMT, DRD2, DTNBP1, GAD1, GRIA1, GRIN2B, HTR2A, NRG1, RELN, SNAP-25, TNIK), brain development, myelination, cell adhesion, glutamate receptor signaling, G-protein-coupled receptor signaling and cAMP-mediated signaling as key to pathophysiology and as targets for therapeutic intervention. Overall, the data are consistent with a model of disrupted connectivity in schizophrenia, resulting from the effects of neurodevelopmental environmental stress on a background of genetic vulnerability. In addition, we show how the top candidate genes identified by CFG can be used to generate a genetic risk prediction score (GRPS) to aid schizophrenia diagnostics, with predictive ability in independent cohorts. The GRPS also differentiates classic age of onset schizophrenia from early onset and late-onset disease. We also show, in three independent cohorts, two European American and one African American, increasing overlap, reproducibility and consistency of findings from single-nucleotide polymorphisms to genes, then genes prioritized by CFG, and ultimately at the level of biological pathways and mechanisms. Finally, we compared our top candidate genes for schizophrenia from this analysis with top candidate genes for bipolar disorder and anxiety disorders from previous CFG analyses conducted by us, as well as findings from the fields of autism and Alzheimer. Overall, our work maps the genomic and biological landscape for schizophrenia, providing leads towards a better understanding of illness, diagnostics and therapeutics. It also reveals the significant genetic overlap with other major psychiatric disorder domains, suggesting the need for improved nosology.

Investigation on the potential of applying bio-based edible coatings for horticultural products exemplified with cucumbers.

Plastic packaging for fresh horticultural produce has many advantages but generates plastic waste and ecological alternatives are required. Edible coatings can retard many processes related to loss of quality. Hydrophobic lipid-based coatings are preferably applied for fresh fruits and vegetables. The approval of such coatings for products with edible peels in EU is increasingly under discussion. However, investigations on the efficiency of various edible coatings on soft-skinned fruit and vegetables are rare and it is currently unclear whether the consumer will accept them. Therefore, this study investigates (1) important characteristics of a lipid-based coating and (2) its ability to maintain the post-harvest quality of fresh cucumbers. This was evaluated by a comparative storage test under common suboptimal retail conditions (20 °C; 65% RH). The study also evaluates (3) the general perception of consumers about and their acceptance of the application of edible coatings on fresh fruit and vegetables with edible peels. The investigated coating was able to drastically reduce water loss (54-68%) and fruit respiration (approx. 33%) of fresh cucumber. The reduction of tissue stiffness was delayed by 2 days, thus, prolonged shelf life. Majority of consumer (77%) endorse the application of edible coatings as an alternative to plastic packaging, but emphasized important requirements for them.

Identification of blood biomarkers for psychosis using convergent functional genomics.

There are to date no objective clinical laboratory blood tests for psychotic disease states. We provide proof of principle for a convergent functional genomics (CFG) approach to help identify and prioritize blood biomarkers for two key psychotic symptoms, one sensory (hallucinations) and one cognitive (delusions). We used gene expression profiling in whole blood samples from patients with schizophrenia and related disorders, with phenotypic information collected at the time of blood draw, then cross-matched the data with other human and animal model lines of evidence. Topping our list of candidate blood biomarkers for hallucinations, we have four genes decreased in expression in high hallucinations states (Fn1, Rhobtb3, Aldh1l1, Mpp3), and three genes increased in high hallucinations states (Arhgef9, Phlda1, S100a6). All of these genes have prior evidence of differential expression in schizophrenia patients. At the top of our list of candidate blood biomarkers for delusions, we have 15 genes decreased in expression in high delusions states (such as Drd2, Apoe, Scamp1, Fn1, Idh1, Aldh1l1), and 16 genes increased in high delusions states (such as Nrg1, Egr1, Pvalb, Dctn1, Nmt1, Tob2). Twenty-five of these genes have prior evidence of differential expression in schizophrenia patients. Predictive scores, based on panels of top candidate biomarkers, show good sensitivity and negative predictive value for detecting high psychosis states in the original cohort as well as in three additional cohorts. These results have implications for the development of objective laboratory tests to measure illness severity and response to treatment in devastating disorders such as schizophrenia.

[Intracellular signaling transduction pathways. Potential targets in the treatment of rheumatic diseases]. / Intrazelluläre Signaltransduktionswege. Potenzielle Angriffspunkte für rheumatologische Therapeutika.

Even though biologics, frequently combined with conventional DMARD therapy, represent a significant advance in the treatment of rheumatic diseases, they have disadvantages such as high costs of production and parenteral administration. Therefore, oral small-molecule drugs are a potential alternative. Major targets for such small-molecule therapeutics are intracellular signaling molecules. This article will briefly discuss potential intracellular targets for therapeutics in the field of rheumatic diseases. How therapeutic signaling inhibitors will be used in clinical practice will depend on a number of factors: their overall effectiveness, their effectiveness in patients who did not or insufficiently respond to conventional DMARD therapy and/or treatment with biologics, their effectiveness when combined with other therapeutics, their side effects, and their cost-benefit ratio.The English full-text version of this article is available at SpringerLink (under "Supplemental").

Rapidly progressive hepatic alveolar echinococcosis in an ABO-incompatible renal transplant recipient.

We report on the case of an ABO-incompatible renal re-transplant recipient maintained on an intensified immunosuppressive regimen for recurrent cellular rejection episodes and transplant glomerulopathy who presented with rapidly growing hepatic tumors, radiologically suggestive of hemangiosarcoma. Upon resection and pathological work-up, the lesions revealed alveolar echinococcosis, a rare but potentially life-threatening parasitosis. Usually infection with Echinococcus multilocularis remains asymptomatic for extended periods of time and can go unrecognized for years. In the case presented, we observed an atypically rapid growth pattern of E. multilocularis that might have been due to the extent of the immunosuppressive regimen, which included repetitive anti-CD20 treatments. Retrospectively performed serological studies with enzyme-linked immunosorbent assays known to provide high sensitivity and specificity for the detection of echinococcosis in the general population, yielded ambiguous results in our immunocompromised host, which could be, in part, explained by B-cell depletion and its effects on antibody production and indirect actions on cellular immunity. In conclusion, this is the first report to our knowledge of hepatic alveolar echinococcosis in a renal transplant recipient. This case documents an altered clinical course of the parasitosis and the challenge of serological diagnostic tools under an intensified regimen of immunosuppressive agents, including rituximab.

Consensus of microbiology reporting of ear swab results to primary care clinicians in patients with otitis externa.

Otitis externa is a ubiquitous inflammatory disease; although it arises most commonly from an infection, there is no consensus in the UK for the reporting of ear swab culture results. This study aims to review current microbiology laboratory reporting of ear swab specimens to primary care and reach an evidence-based consensus for a reporting policy. Fifty consecutive ear swab reports were reviewed from each of 12 laboratories in the South West region to determine and discuss reporting practice. The Health Protection Agency (HPA) GP Microbiology Laboratory Use Group reviewed the underlying evidence and worked towards a consensus of expert microbiology opinion for laboratory reporting of ear swab results using a modified version of the Delphi technique. A total of 487 reports from primary care were reviewed (54% female; 46% male). Cultures most commonly yielded Pseudomonas species (36%), Staphylococcus species (21%), Streptococcus species (15%) and fungi (11%). Five reporting policies were agreed: Policy 1: Common pathogens such as group A beta-haemolytic streptococci, Streptococcus pneumoniae, Staphylococcus aureus - Always reported by name with antibiotic susceptibilities. Policy 2: Pseudomonas species - Always reported, but antibiotic susceptibilities only reported in severe disease. Policy 3: Aspergillus, Candida, coliforms and Proteus species, as well as non-group A streptococci and anaerobes - Only reported if moderate numbers of colonies and it is the predominant organism present; if appropriate report antibiotic susceptibilities. Policy 4: Coagulase-negative staphylococci, diphtheroids and enterococci - Not reported by name; generic terms used and antibiotic susceptibilities not reported. Policy 5: When antibiotic susceptibilities reported these must include susceptibility to a topical antibiotic. It is suggested that laboratories should consider adopting this evidence-based reporting consensus for ear swab culture results from primary care patients with otitis externa.

[Surgical treatment of snapping triceps syndrome]. / Die operative Therapie des Snapping-Trizeps-Syndroms.

OBJECTIVE: Treatment of a persistently painful snapping triceps and possibly snapping ulnar nerve. INDICATION: Snapping triceps. CONTRAINDICATIONS: General surgical risks. SURGICAL TECHNIQUE: Following the anterior transposition of the ulnar nerve (subcutaneously or submuscular), the snapping portion of the triceps tendon is transsected and reinforced, and transposition of the medial triceps margin into the central triceps portion is carried out. POSTOPERATIVE MANAGEMENT: Cast for 5-7 days; for a total of 6 weeks functional exercise without maximum flexion and resistance exercise of the triceps. Weight loading after 3 months. RESULTS: In the case presented, complaints were absent after 3 months. Full load exercise, e.g., push-ups, was achieved 4 months after surgery. There was no recurrent snapping within the first year. The results of this case are in agreement with the 25 patients previously reported in the PubMed literature. Recurrence, gross restrictions of movement, and complications were not observed in patients who underwent surgery.

Differential transcriptome analysis of intraarticular lesional vs intact cartilage reveals new candidate genes in osteoarthritis pathophysiology.

OBJECTIVE: To elucidate disease-specific molecular changes in osteoarthritis (OA) by analyzing the differential gene expression profile of damaged vs intact cartilage areas within the same joint of patients with OA of the knee using a combination of a novel RNA extraction technique and whole-genome oligonucleotide arrays. METHODS: The transcriptome of macroscopically affected vs intact articular cartilage as determined by visual assessment was analyzed using an optimized mill-based total RNA isolation directly from the tissue and high density synthetic oligonucleotide arrays. Articular cartilage samples were obtained from patients with OA of the knee. Expression of differentially regulated genes was validated by real-time quantitative polymerase chain reaction and immunohistochemistry. RESULTS: The amount of RNA obtained by the optimized extraction procedure was at least 1 microg per 500 mg of cartilage and fulfilled the common quality requirements. After hybridization onto HG-U133 Plus 2.0 GeneChips (Affymetrix), 28.6-51.7% of the probe sets on the microarray showed a detectable signal above the signal threshold in the individual samples. A subset of 411 transcripts, which appeared to be differentially expressed, was obtained when applying predefined filtering criteria. Of these, six genes were found to be up-regulated in the affected cartilage of all patients, including insulin-like growth factor binding protein 3 (IGFBP-3), wnt-1-inducible signaling protein 1 (WISP-1), aquaporin 1 (AQP-1), delta/notch-like EGF-repeat containing transmembrane (DNER), decay accelerating factor (DAF), complement factor I (IF). CONCLUSION: The optimized methodical approach reported here not only allows to determine area-specific gene expression profiles of intraindividually different low-RNA containing OA cartilage specimens. In addition, this study also revealed novel genes not yet reported to play a role in the pathophysiology of joint destruction in OA.

Strain differences during intraventricular infusion of norepinephrine: possible role of receptor sensitivity.

Two rat strains previously shown to differ with respect to behavioral activity, regional brain tyrosine hydroxylase activity, and norepinephrine-elicited accumulation of adenosine 3', 5'-monophosphate exhibited differential behavioral responsiveness during the intraventricular infusion of norepinephrine. The results are interpreted in terms of differential catecholamine receptor sensitivity.

Increased exploratory activity and altered response to LSD in mice lacking the 5-HT(5A) receptor.

In order to determine the distribution and function of the 5-HT5A serotonin receptor subtype, we generated knockout mice lacking the 5-HT5A gene. Comparative autoradiography studies of brains of wild-type (wt) and 5-HT5A knockout (5A-KO) mice revealed the existence of binding sites with high affinity for [125I]LSD that correspond to 5-HT5A receptors and that are concentrated in the olfactory bulb, neocortex, and medial habenula. When exposed to novel environments, the 5A-KO mice displayed increased exploratory activity but no change in anxiety-related behaviors. In addition, the stimulatory effect of LSD on exploratory activity was attenuated in 5A-KO mice. These results suggest that 5-HT5A receptors modulate the activity of neural circuits involved specifically in exploratory behavior and suggest that some of the psychotropic effects of LSD may be mediated by 5-HT5A receptors.

Developing translational animal models for symptoms of schizophrenia or bipolar mania.

Animal models have long been used to explore hypotheses regarding the neurobiological substrates of and treatments for psychiatric disorders. Early attempts to develop models that mimic the entirety of the diagnostic syndromes in psychiatry have evolved into more appropriate efforts to model specific symptoms. Such an approach reflects the facts that even in patients, clinical symptoms transcend diagnostic categories, and the specific etiologies of psychiatric disorders are unknown. An animal model can only be identified adequately by specifying both the manipulation (drug, lesion, strain) used to induce abnormalities and the measure(s) used to characterize them. A wide range of pharmacological, lesion, and developmental manipulations have been combined with various measures of information processing to develop useful animal models that parallel human tests. Prepulse inhibition of startle, event-related potential (ERP) measures of auditory gating, and Cambridge neuropsychological test automated battery (CANTAB) measures of cognition are examples of measures that can be used in both rodents and humans and that are robustly altered in both psychiatric disorders and animals manipulated with appropriate drugs or lesions. The further development of cross-species models is critically important, given the new opportunities for the development and registration of specific treatments for the cognitive disorders of schizophrenia that are not ameliorated by available drugs. In moving beyond the focus on psychotic symptoms to the cognitive symptoms of schizophrenia, animal models that do not involve manipulations of dopamine D(2) receptors but that do utilize information processing measures that are correlated with cognitive disturbances are receiving increased attention. Here, selected examples of how cross-species measures of psychiatric disorders are developed and validated are discussed. Specific animal paradigms that parallel the specific domains of cognition that are altered in schizophrenia provide one focus of the review. Another focus includes efforts to develop new human models of psychiatric symptoms that are designed to parallel existing tests used in rodents.

Effect of yacon (Smallanthus sonchifolius) on colonic transit time in healthy volunteers.

BACKGROUND: Yacon is a root crop which contains high amounts of fructooligosaccharides (FOS). The aim of this study was to investigate the effects of yacon syrup on colon transit time in healthy volunteers. METHODS: In a placebo-controlled, double-blind study yacon was administered to 16 healthy individuals (8 males, 8 females) in a dose of 20 g daily (equal to 6.4 g FOS) in a 2-week crossover design. Each period was interrupted by a 2-week wash-out phase. Transit time was assessed by a radio-opaque marker technique. RESULTS: Transit time (mean +/- SEM) through the gastrointestinal tract was significantly decreased from 59.7 +/- 4.3 to 38.4 +/- 4.2 h (p < 0.001). Yacon was well tolerated with an excellent side effect profile. Bloating is not an uncommon side effect observed with FOS, but bloating-related disturbances were not significantly more often reported with yacon compared to placebo. Stool frequency increased from 1.1 +/- 0.1 to 1.3 +/- 0.2 times per day and the consistency showed a tendency for softer stools as assessed by a numerical depicted stool protocol. Neither parameter did, however, reach statistical significance. CONCLUSION: Yacon markedly accelerates colonic transit in healthy individuals. Further studies are needed in constipated patients to confirm these preliminary data. Due to the low caloric content of yacon, the root could be a useful treatment in constipated diabetics or obese patients.

Phenomic, convergent functional genomic, and biomarker studies in a stress-reactive genetic animal model of bipolar disorder and co-morbid alcoholism.

We had previously identified the clock gene D-box binding protein (Dbp) as a potential candidate gene for bipolar disorder and for alcoholism, using a Convergent Functional Genomics (CFG) approach. Here we report that mice with a homozygous deletion of DBP have lower locomotor activity, blunted responses to stimulants, and gain less weight over time. In response to a chronic stress paradigm, these mice exhibit a diametric switch in these phenotypes. DBP knockout mice are also activated by sleep deprivation, similar to bipolar patients, and that activation is prevented by treatment with the mood stabilizer drug valproate. Moreover, these mice show increased alcohol intake following exposure to stress. Microarray studies of brain and blood reveal a pattern of gene expression changes that may explain the observed phenotypes. CFG analysis of the gene expression changes identified a series of novel candidate genes and blood biomarkers for bipolar disorder, alcoholism, and stress reactivity.

Novel Insights into the Pathogenesis of Osteoarthritis.

Osteoarthritis represents the most frequently diagnosed condition of the musculoskeletal system and accounts for a high amount of direct and indirect socioeconomic costs worldwide. While for rheumatoid arthritis much progress has been made in the past decades both in understanding its pathogenesis and in creating novel therapies, the pathophysiology of osteoarthritis still holds several secrets to be unraveled in the near future in order to also allow for the development of effective novel pharmacotherapeutical options. Though first categorized as a joint disorder being primarily non-inflammatory in nature for a long period of time with research focused on biomechanic aspects and imbalanced wear and tear, recent evidence including immunological processes helped to refine disease interpretation. Thus, showing true inflammatory characteristics that clinically emerge as synovitis, osteoarthritis is nowadays recognized to include signs of inflammation that at least histologically may sometimes be indistinguishable from rheumatoid synovial infiltration. Although this was known already more than 25 years ago, efforts made in solving pathophysiologic key issues did not succeed sufficiently. This review is thought to summarize elementary pathogenic aspects including genetic predisposition and epigenetic regulation and highlights important central innate but also putative adaptive immunological mechanisms today generally accepted to drive inflammation and tissue destruction in osteoarthritis.

Impaired postnatal development of hippocampal dentate gyrus in Sp4 null mutant mice.

Sp4, a member of the Sp1 family of transcription factors, is expressed restrictively in the developing nervous system and abundantly in the hippocampus. Previously, we demonstrated that hypomorphic Sp4 mice display hippocampal vacuolization and concomitant deficits in memory and sensorimotor gating. Here, we report further analyses of Sp4 functions during postnatal development of the dentate gyrus in Sp4 null mutant mice. A reduced cell proliferation restrictively in hippocampus, but not cerebellum, was observed in the first week of postnatal development of Sp4 null mutant mice. The dendritic growth and arborization of dentate granule cells was decreased in hippocampal cultures in vitro from mutant neonatal mice. The adult Sp4 null mutant mice displayed decreased dentate granule cell density with reduced width of both dentate gyrus and the molecular layer. The abnormality of the molecular layer was indicated by a reduced level of synaptophysin expression in the mutant mice. The Sp4 transcription factor therefore appears to predominantly regulate the development of dentate granule cells.