First record of Trichophyton benhamiae isolated from domestic cats in Russia.

We report a first case of Trichophyton benhamiae isolation from domestic cats in Russia. Genetically affiliated to European strains T. benhamiae were deposited in NCBI. T. benhamiae strains formed zonal cream-colored colonies, with reversum pigmentation ranging from intensive yellow to orange-brown in one and orange-brown to chocolate in the second strain. Mycelium is colorless, hyphae are septated, rapidly aging with the formation of arthrospores and microconidia. The formation of macroconidia was recorded after 48 hours. A favorable outcome of treatment was recorded after two weeks.

Highly Atherogenic Lipid Particles are Associated with Preeclampsia After Successful Fertility Treatment for Obese Women who have Unexplained Infertility.

Atherogenic dyslipidemia-before or during pregnancy-may contribute to preeclampsia and subsequent cardiovascular disease risk. We performed a nested case-control study to further understand dyslipidemia associated with preeclampsia. The cohort consisted of participants in the randomized clinical trial "Improving Reproductive Fitness Through Pretreatment with Lifestyle Modification in Obese Women with Unexplained Infertility" (FIT-PLESE). FIT-PLESE was designed to study the effect of a pre-fertility treatment 16-week randomized lifestyle intervention program (Nutrisystem diet + exercise + orlistat vs. training alone) on improvement in live birth rate among obese women with unexplained infertility. Of the 279 patients in FIT-PLESE, 80 delivered a viable infant. Maternal serum was analyzed across five visits: before and after lifestyle interventions and also at three pregnancy visits (16, 24, and 32 weeks gestation). Apolipoprotein lipids were measured in a blinded fashion using ion mobility. Cases were those who developed preeclampsia. Controls also had a live birth but did not develop preeclampsia. Generalized linear and mixed models with repeated measures were used to compare the mean lipoprotein lipid levels of the two groups across all visits. Complete data were available for 75 pregnancies, and preeclampsia developed in 14.5% of the pregnancies. Cholesterol/high-density lipoprotein (HDL) ratios (p < 0.003), triglycerides (p = 0.012), and triglyceride/HDL ratios, all adjusted for BMI, were worse in patients with preeclampsia (p < 0.001). Subclasses a, b, and c of highly atherogenic, very small, low-density lipoprotein (LDL) particles were higher during pregnancy for the preeclamptic women (p < 0.05). Very small LDL particle subclass d levels were significantly greater only at 24 weeks (p = 0.012). The role of highly atherogenic, very small LDL particle excess in the pathophysiology of preeclampsia awaits further investigation.

[Small salivary glands in the paratonsillar space in children]. / Malye slyunnye zhelezy v paratonzillyarnom prostranstve u detei.

THE AIM OF THE STUDY: Was to study the changes in the small salivary glands in chronic tonsillitis and paratonsillar abscess in children. A histological examination of the palatine tonsils of 22 children aged 5 to 14 years old who had a paratonsillar abscess and 18 children suffering from chronic tonsillitis was carried out. Fragments of small salivary glands, located both superficially, in the mucous membrane between the stratified squamous non-keratinizing epithelium and the lymphoid tissue of the palatine tonsils, and between the muscles of the amygdala were found in 42 of the 80 (52.5%) tonsils studied. Along with the unchanged glandular structure, 26 (61.9%) samples revealed areas of destruction foci in small salivary glands with signs of inflammatory and compensatory regenerative activity. The presence of separate interlobular ducts of the salivary glands with pronounced periductal lymph - macrophage infiltration was noted. The subepithelial lymph-macrophage infiltrates found in the lamina propria are associated with the exit of the excretory ducts of the salivary glands to the surface of the mucous membrane. Many thin-walled veins are surrounded by perivascular lymphocellular infiltrates. The inflammatory and post-inflammatory changes in the small salivary glands revealed by us in children with chronic tonsillitis do not exclude their participation in the pathogenesis of paratonsillitis. At the same time, inflammation in the salivary gland can be both primary, as a result of its infection with live microorganisms from the tissues of the tonsil, and secondary, due to the compression of the excretory ducts by the edematous tissue of the tonsil in acute tonsillitis.

Specifying the neural basis of the spacing effect with multivariate ERP.

The spacing effect refers to the finding that, given a fixed amount of study time, a longer interval between study repetitions improves long-term retention (e.g., Cepeda et al., 2006; Ebbinghaus, 1885/1967; Melton, 1970). Although the spacing effect is a robust and reliable finding in the memory literature, its cognitive and neural mechanisms remain unclear. We used event-related potentials (ERPs) to investigate the neural correlates of the spacing effect in the context of the study-phase retrieval hypothesis, which posits that repeated exposure of an item serves as a reminder of one's previous experience with the item, thereby promoting long-term retention. ERPs were recorded from 30 healthy young adults as they studied pairs of words under three levels of lag, corresponding to 0, 4, or 12 intervening pairs between the first and second occurrences of a target pair. We used two study-phase tasks that differed in the degree of retrieval that was required. During the test phase, participants were tested on paired-associate recall. The results demonstrated a significant effect of spacing on memory performance. However, the effect of encoding task and the interaction between encoding task and spacing were not significant. The results of the partial least squares analyses, which are not constrained by time window or electrode selection, revealed a spacing effect on the ERP data for both study-phase tasks; this effect occurred late in the epoch and was most salient over the centro-parietal scalp region. The results add to the literature on the neural correlates of the spacing effect by providing a more comprehensive account compared to past ERP findings that were focused on testing specific ERP components. They also call for further investigation on the various theoretical accounts of the spacing effect.

[Proinflammatory cytokine content in the saliva of children suffering from chronic tonsillitis]. / Soderzhanie provospalitel'nykh tsitokinov v sliune detei s khronicheskim tonzillitom.

INTRODUCTION: We have examined 92 children aged between 6 and 15, suffering from chronic tonsillitis (CT). Tumor necrosis factor (TNF-α) and interleukin 1ß and 6 (IL-1ß and IL-6) contents have been defined in saliva. The control set comprised 17 healthy children. Cytokine content was defined with the enzyme multiplied immunoassay sets (Vektor Best Ltd., Russia) by enzyme-linked immunosorbent assay. The statistic analysis and data processing were carried out with statistic analysis programs (version 3.2, R Foundation for Statistical Computing, Vienna, Austria). RESULTS: The content of cytokines TNF-α, IL-1, IL-6 in CT children's saliva was high against the healthy children, yet the statistically significant differences were only noted for IL-6. In the CT group the median value of this factor (12.5) was significantly higher than in the control set (6.72) (p=0.01 in Mann-Whitney assessment). IL-6 was chosen as the basic factor for the mathematic model; its combinations in the form of a multi-factor logistic regression were given consideration. From out of the three possible models there was just one that had all the coefficients statistically significantly different from zero (TNF-α - IL-6). It was chosen as the basic diagnostic model for chronic tonsillitis. The created model's sensitivity is 80.4%, while its specificity is 82.4%. DISCUSSION: The revealed IL-6 dominance in saliva at CT can be is attributable to permanent antigenic challenge characteristic of the toxic allergic CT since, as previously shown, there are living proliferating microorganisms in the palatal tonsil tissues and their blood- and lymph vessels at CT. CONCLUSION: The conducted ROC-analysis has demonstrated high sensitivity and specificity of the mathematical model, which enabled us to recommend determination of IL-6 in the saliva of the children suffering from CT as an additional diagnostic criterion.

A Systematic Review of Exposure to Bisphenol A from Dental Treatment.

INTRODUCTION: Dental composite restorations and dental sealants containing bisphenol A glycidyl methacrylate (BisGMA) are commonly used materials in dentistry. Bisphenol A (BPA) is used to manufacture BisGMA and can be a by-product in BisGMA-based dental materials. BPA is an endocrine-disrupting chemical that may affect reproductive, psychological, cognitive, and endocrine-related health. We conducted a systematic review of clinical studies that measured urinary BPA (uBPA) concentrations before and after dental treatment to evaluate the extent to which individuals are exposed to BPA from dental treatment. METHODS: Eligibility included studies that measured uBPA concentrations before and after dental treatment with any type of resin-based dental material. We searched PubMed, Cochrane, Web of Science, Virtual Health Library, Science Direct, ProQuest, and Clinical Trials with no date or language restrictions to identify published studies. We summarized eligible studies across participant characteristics, amount of treatment, and time of follow-up measures. Because methods of measuring uBPA varied, our primary outcome was the direction and percentage change between baseline and 24 h posttreatment and at later time points as available. RESULTS: We identified 1,190 abstracts and 7 eligible studies: 4 in children and 3 in adults. In all studies, BPA concentrations increased 24 h after treatment. The 2 studies with the largest sample sizes found statistically significant increases >40% in uBPA concentrations at 24 h posttreatment (both P values <0.01). The 1 study to examine uBPA concentrations beyond 1 mo posttreatment found that concentrations returned to baseline by 14 d after treatment and remained at baseline 6 mo after treatment. CONCLUSIONS: Our findings suggest that uBPA concentrations increase 24 h after dental treatment. One study showed that uBPA concentrations return to baseline by 14 d. Additional research is needed to determine the magnitude of change from pre- to post-dental treatment and the trajectory of uBPA concentrations posttreatment. KNOWLEDGE TRANSFER STATEMENT: BPA is an endocrine-disrupting chemical that may have negative human health effects. Our findings suggest that urinary BPA concentrations increase in the short term after dental treatment. The extent to which such an increase may affect the health of patients remains an open question, particularly since there are no established thresholds for safety or harm related to BPA exposure.

The spacing effect stands up to big data.

Many studies have shown that repetition of study material with temporal gaps between the repetitions (i.e., spaced in time) is more effective for long-term retention than are repetitions in immediate succession (i.e., massed; Greene, 1989). Although this spacing effect has proven to be robust in the laboratory (Cepeda, Pashler, Vul, Wixted, & Rohrer, 2006), its status in the real world is relatively understudied. Other research has demonstrated the benefit of memory retrieval on subsequent retrieval of the same information (Bjork, 1975, 1988; Roediger & Karpicke, 2006), referred to as the testing effect. However, it is not clear how spacing and retrieval can be optimally combined in order to enhance knowledge retention in a real-world setting. To investigate this question, we analyzed longitudinal data from 10,514 individuals, collected in the context of naturally occurring workplace training. To determine the impact of spaced retrieval on knowledge retention, these data were analyzed using a generalized linear mixed model with the following fixed factors: (1) spacing interval between repetitions of content training (retrieval practice), (2) retention interval, and (3) question format. Random factors included the specific content on which employees were trained, which was clustered by employee and, in turn, by company, resulting in a three-level hierarchy. The results showed a significant interaction between spacing interval and retention interval: the optimal amount of spacing between repeated retrieval events increased as the retention interval increased. These findings are in line with the results of laboratory studies, demonstrating the relevance and transferability of laboratory-based research to real-world contexts.

[The significance of antistreptolysin O characteristics for the determination of indications for tonsillectomy in the children]. / Znachenie pokazatelei antistreptolizina O pri opredelenii pokazanii k tonzilléktomii u detei.

The objective of the present work was to evaluate the diagnostic significance of the measurement of the antistreptolysin O (ASLO) titers in the children presenting with chronic tonsillitis for determining the indications for tonsillectomy. The study included 54 patients at the age varying from 4 to 17 years who had undergone bilateral tonsillectomy for the treatment of chronic tonsillitis. The diagnosis was confirmed by the results of the histological study of the removed amygdalae. Prior to surgery, all the patients had been subjected to the bacteriological investigation of the smears taken from the surface of the palatal tonsils. The titers of antistreptolysin O in the serum were determined with the use of the kinetic nephelometric technique before, 6 and 12 months after the surgical intervention. The results of the measurements were treated using the Statzilla software package (version 3.2, R Foundation for Statistical Computing, Vienna, Austria). Streptococcus pyogenes (group A) was identified only in 7 (13%) patients. The initially enhanced content of ASLO ranging from 273 to 1880 IU/ml was documented in 42 (77.7%) of the 54 patients. Twelve patients had the ASLO titers within the normal limits (from 13 to 124 IU/ml). The removal of palatal tonsils resulted in a significant decrease of the ASLO titers in the patients who had presented with the initially enhanced content of antistreptolysin O (p < 0.05); nevertheless, their ASLO titers remained higher than the normal values in 69% and 82% of the patients examined within 6 and 12 months after the surgical intervention, respectively. The patients who had exhibited the high levels of antistreptolysin O during the preoperative period did not experience normalization of this parameter after surgery. It is concluded, taking into account the absence of correlation between the enhancement of serum antistreptolysin O titers and the presence of group A beta-chemolytic Streptococci (BCSA), that the result of the measurement of ASLO titers can not be considered as a valid indication for tonsillectomy in the children.

Global partnerships are critical to advance the control of Neglected Zoonotic Diseases: The case of the Global Alliance for Rabies Control.

There is a need for innovation to improve control of all Neglected Zoonotic Diseases (NZDs). The Global Alliance for Rabies Control was formed to prevent human deaths from rabies and relieve the burden of rabies in other animal populations, especially dogs. It aims to identify reasons for the neglect of rabies in developing countries and to develop strategies to improve rabies control. Through initiatives such as World Rabies Day and the Partners for Rabies Prevention, progress has been made towards increased awareness of the burden of rabies transmitted by dogs at scales from local to international. An evidence base of the feasibility of canine rabies elimination has been built up and now easier access to information and tools enables countries to design and implement rabies elimination strategies in a logical way, utilizing the structures of regional networks for rabies control. The body of evidence has built consensus amongst international stakeholders in rabies control and is now being used to encourage international policy change, attract investment and increase delivery of effective rabies control programmes in canine rabies endemic countries.

Dental and Temporomandibular Joint Pathology of the California Mountain Lion (Puma concolor couguar).

Skulls from 91 California mountain lions (Puma concolor couguar) were examined macroscopically and radiographically. The majority of the skulls were from young adult animals (57.1%). The skull specimens were from 42 male (46.1%) and 34 female (37.4%) animals, while the gender was unknown for the remainder. The majority (94.5%) of teeth were present for examination. Only 11 teeth were identified as absent congenitally; five of these teeth were maxillary first molar teeth and three were maxillary second premolar teeth. Abnormal tooth morphology was identified in 3.5% of teeth. The most common abnormality in tooth form was abnormally large crowns of the maxillary first molar teeth. Teeth with an abnormal number of roots were uncommon (n = 21). Ninety-one teeth were found to have an abnormal number of roots, most often two-rooted maxillary first molar teeth instead of the expected one root. The most prevalent dental lesions found in the California mountain lion were attrition/abrasion (93.4%), tooth fractures (80.2%) and periodontitis (38.5%). Less common dental lesions were tooth resorption (n = 32 teeth) and endodontal disease (n = 29 teeth).

Dental Pathology of the California Bobcat (Lynx rufus californicus).

Skulls from 277 California bobcats (Lynx rufus californicus) were examined macroscopically and by radiography. The majority of the skulls were from adult animals (79.8%). The skulls were from 128 male (46.2%) and 114 female (41.2%) animals and gender was unknown for the remainder. The majority (95.6%) of teeth were present for examination. Only 16 teeth were identified as absent congenitally and 15 of these were incisor teeth. Teeth with abnormal morphology were rare (0.5%). The two most common abnormalities were unusually large crowns of the maxillary first molar teeth and bigemination of the mandibular incisor teeth. Teeth with an abnormal number of roots were uncommon (n = 68). Sixty-three teeth had abnormal roots, mostly the presence of two roots instead of one for the maxillary first molar tooth. The most prevalent dental lesions found in the California bobcat were attrition/abrasion (85.2%), periodontitis (56.0%) and tooth fractures (50.9%). Less common dental lesions were endodontal disease (n = 114 teeth) and tooth resorption (n = 73 teeth).

World Rabies Day - a decade of raising awareness.

World Rabies Day was set up in 2007 to raise global awareness about rabies, to provide information on how to prevent the disease in at-risk communities and support advocacy for increased efforts in rabies control. It is held annually on September 28th, with events, media outreach and other initiatives carried out by individuals, professionals, organisations and governments from the local to the international level. The Global Alliance for Rabies Control coordinates World Rabies Day, amplifying the campaign's reach through the provision of a central event platform and resources to support events across the world, the promotion of messages through key rabies stakeholders, and the implementation of specific activities to highlight particular issues. Over the last decade, more than 1,700 registered events have been held across the world and shared with others in the global rabies community. Events in canine rabies endemic countries, particularly in Africa and Asia, have increased over time. Beyond the individual events, World Rabies Day has gained the support of governments and international agencies that recognise its value in supporting existing rabies control initiatives and advocating for improvements. As the rabies landscape has changed, World Rabies Day remains a general day of awareness but has also become an integral part of national, regional and global rabies elimination strategies. The global adoption of 2030 as the goal for the elimination of rabies as a public health threat has led to even greater opportunities for World Rabies Day to make a sustainable impact on rabies, by bringing the attention of policy makers and donors to the ongoing situation and elimination efforts in rabies-endemic countries.

Early stroke risk and ABCD2 score performance in tissue- vs time-defined TIA: a multicenter study.

OBJECTIVES: Stroke risk immediately after TIA defined by time-based criteria is high, and prognostic scores (ABCD2 and ABCD3-I) have been developed to assist management. The American Stroke Association has proposed changing the criteria for the distinction between TIA and stroke from time-based to tissue-based. Research using these definitions is lacking. In a multicenter observational cohort study, we have investigated prognosis and performance of the ABCD2 score in TIA, subcategorized as tissue-positive or tissue-negative on diffusion-weighted imaging (DWI) or CT imaging according to the newly proposed criteria. METHODS: Twelve centers provided data on ABCD2 scores, DWI or CT brain imaging, and follow-up in cohorts of patients with TIA diagnosed by time-based criteria. Stroke rates at 7 and 90 days were studied in relation to tissue-positive or tissue-negative subcategorization, according to the presence or absence of brain infarction. The predictive power of the ABCD2 score was determined using area under receiver operator characteristic curve (AUC) analyses. RESULTS: A total of 4,574 patients were included. Among DWI patients (n = 3,206), recurrent stroke rates at 7 days were 7.1%(95% confidence interval 5.5-9.1) after tissue-positive and 0.4% (0.2-0.7) after tissue-negative events (p diff < 0.0001). Corresponding rates in CT-imaged patients were 12.8% (9.3-17.4) and 3.0% (2.0-4.2), respectively (p diff < 0.0001). The ABCD2 score had predictive value in tissue-positive and tissue-negative events (AUC = 0.68 [95% confidence interval 0.63-0.73] and 0.73 [0.67-0.80], respectively; p sig < 0.0001 for both results, p diff = 0.17). Tissue-positive events with low ABCD2 scores and tissue-negative events with high ABCD2 scores had similar stroke risks, especially after a 90-day follow-up. CONCLUSIONS: Our findings support the concept of a tissue-based definition of TIA and stroke, at least on prognostic grounds.

AMP-activated protein kinase: a core signalling pathway in the heart.

Over the past decade, AMP-activated protein kinase (AMPK) has emerged as an important intracellular signalling pathway in the heart. Activated AMPK stimulates the production of ATP by regulating key steps in both glucose and fatty acid metabolism. It has an inhibitory effect on cardiac protein synthesis. AMPK also interacts with additional intracellular signalling pathways in a coordinated network that modulates essential cellular processes in the heart. Evidence is accumulating that AMPK may protect the heart from ischaemic injury and limit the development of cardiac myocyte hypertrophy to various stimuli. Heart AMPK is activated by hormones, cytokines and oral hypoglycaemic drugs that are used in the treatment of type 2 diabetes. The tumour suppressor LKB1 is the major regulator of AMPK activity, but additional upstream kinases and protein phosphatases also contribute. Mutations in the regulatory gamma2 subunit of AMPK lead to an inherited syndrome of hypertrophic cardiomyopathy and ventricular pre-excitation, which appears to be due to intracellular glycogen accumulation. Future research promises to elucidate the molecular mechanisms responsible for AMPK activation, novel downstream AMPK targets, and the therapeutic potential of targeting AMPK for the prevention and treatment of myocardial ischaemia or cardiac hypertrophy.

Prospective follow-up oral food challenge in food protein-induced enterocolitis syndrome.

OBJECTIVES: To determine tolerance rates to cow's milk and soy and to suggest guidelines for follow-up oral food challenges (FU-OFCs) in infantile food protein-induced enterocolitis syndrome (FPIES). METHODS: The authors analysed the data of 23 patients with infantile FPIES who underwent two or more FU-OFCs and were followed up until over 2 years of age. The first FU-OFCs were performed at 6 months of age, and patients were randomly allocated to cow's milk (n = 11) or soy (n = 12) challenge starting groups. Second and third FU-OFCs were performed at 2-month intervals in a crossed and switched-over manner. RESULTS: Tolerance rates to cow's milk and soy were 27.3% and 75.0% at 6 months of age, 41.7% and 90.9% at 8 months and 63.6% and 91.7% at 10 months, respectively. Patients outgrew cow's milk and soy intolerance at age 20 and 14 months. CONCLUSIONS: In infantile FPIES, the first FU-OFC should be performed with soy at 6-8 months of age and cow's milk FU-OFC should be conducted at over 12 months of age. Infants with FPIES were observed to outgrow food sensitivities during the first 2 years of life.

Permeate flux inflection due to concentration polarization in crossflow membrane filtration: A novel analytic approach.

A convection-diffusion equation for membrane filtration is analytically solved assuming fast crossflow velocity of a simple shear flow tangential to the membrane surface. In the direction normal to the membrane surface, solute concentration varies in a partially exponential and partially power-wise manner. The permeate flux in an asymptotic limit is proportional to the inverse square root of the distance from the inlet of the membrane channel. Osmotic pressure due to retained solutes on the membrane surface controls the profile of the permeate flux, which undergoes an inflection along the tangential direction if applied pressure is more than four times the feed osmotic pressure.

Liver and circulating NK1.1(+)CD3(-) cells are increased in infection with attenuated Salmonella typhimurium and are associated with reduced tumor in murine liver cancer.

An attenuated (DeltacyA, Deltacrp) strain of Salmonella typhimurium (chi4550) containing a gene for human IL-2 (chi4550pIL2) reduces hepatic tumor burden when orally inoculated into mice with liver cancer; however, wild-type S. typhimurium is also associated with cancer regression. Therefore, experiments were designed to clarify the invasiveness and the anti-tumor properties of three strains of S. typhimurium. S. typhimurium chi4550pIL2, chi4550, or wild type (WT) was incubated with mature Caco-2 and HT-29 enterocytes, and S. typhimurium internalization was assessed. For infectivity experiments, mice were orally inoculated with saline or 10(9)S. typhimurium chi4550pIL2, chi4550, or WT; 48 h later mice were sacrificed for analysis of cecal bacteria and S. typhimurium translocation to mesenteric lymph nodes. For experiments involving tumor implantation, four groups were studied: saline control, tumor alone, chi4550pIL2+tumor, and chi4550+tumor. Mice were orally inoculated with saline or S. typhimurium and underwent laparotomy 24 h later with 5 x 10(4) MCA38 murine adenocarcinoma cells injected into the spleen. On day 14, liver tumors were counted and peripheral blood and hepatic lymphocyte populations were analyzed by FACScan. Attenuated S. typhimurium exhibited decreased internalization by cultured enterocytes and decreased infectivity after oral inoculation. Mice treated with chi4550pIL2 or chi4550 had fewer liver tumors and increased populations of hepatic and circulating NK1.1(+)CD3(-) lymphocytes compared to mice treated with saline (P < 0.01). These data suggest that attenuated S. typhimurium may have an application as an anti-tumor agent.

A slow wave investigation of working memory biases in mood disorders.

Mood-congruent working memory biases were examined in a delayed matching to sample paradigm using the slow wave (SW) event-related brain potential (ERP) component. Mood-congruent working memory biases, indexed by SW amplitudes, were demonstrated among individuals experiencing a major depressive episode (MDE) and nondepressed controls but not individuals with dysthymia. However, analyses of symptom severity demonstrated that those with dysthymia exhibited significantly less negative SW amplitudes with increasing depressive mood severity, whereas individuals with major depression demonstrated more negative SW amplitudes with increasing depressive mood severity. These results are discussed in the context of diagnostic specificity for cognitive biases associated with working memory of mood-disordered individuals.

Wnt receptors and Wnt inhibitors are expressed in gradients in the developing telencephalon.

The caudomedial margin of the medial pallium, known as the cortical hem, expresses several Wnt genes that have been shown to be crucial for cortical development. We examined the expression of members of the Frizzled (mFz) family of Wnt receptors and the Secreted Frizzled Related Protein (SFRP) family of Wnt inhibitors during telencephalic development. We found that mFz-5 and mFz-8 are specifically expressed in the neocortical neuroepithelium and excluded from the hippocampal neuroepithelium in early telencephalic development, whereas mFz-9 and mFz-10 have expression domains confined to the medial pallium. In addition, SFRP-1 and SFRP-3 are expressed in opposing anterolateral to caudomedial gradients within the telencephalic ventricular zone throughout corticogenesis.

Constitutively activating mutation in WASP causes X-linked severe congenital neutropenia.

The Wiskott-Aldrich syndrome protein (WASP; encoded by the gene WAS) and its homologs are important regulators of the actin cytoskeleton, mediating communication between Rho-family GTPases and the actin nucleation/crosslinking factor, the Arp2/3 complex. Many WAS mutations impair cytoskeletal control in hematopoietic tissues, resulting in functional and developmental defects that define the X-linked Wiskott-Aldrich syndrome (WAS) and the related X-linked thrombocytopenia (XLT). These diseases seem to result from reduced WASP signaling, often through decreased transcription or translation of the gene. Here we describe a new disease, X-linked severe congenital neutropenia (XLN), caused by a novel L270P mutation in the region of WAS encoding the conserved GTPase binding domain (GBD). In vitro, the mutant protein is constitutively activated through disruption of an autoinhibitory domain in the wild-type protein, indicating that loss of WASP autoinhibition is a key event in XLN. Our findings highlight the importance of precise regulation of WASP in hematopoietic development and function, as impairment versus enhancement of its activity give rise to distinct spectra of cellular defects and clinical phenotypes.