Human Purkinje cells outperform mouse Purkinje cells in dendritic complexity and computational capacity.

Purkinje cells in the cerebellum are among the largest neurons in the brain and have been extensively investigated in rodents. However, their morphological and physiological properties remain poorly understood in humans. In this study, we utilized high-resolution morphological reconstructions and unique electrophysiological recordings of human Purkinje cells ex vivo to generate computational models and estimate computational capacity. An inter-species comparison showed that human Purkinje cell had similar fractal structures but were larger than those of mouse Purkinje cells. Consequently, given a similar spine density (2/µm), human Purkinje cell hosted approximately 7.5 times more dendritic spines than those of mice. Moreover, human Purkinje cells had a higher dendritic complexity than mouse Purkinje cells and usually emitted 2-3 main dendritic trunks instead of one. Intrinsic electro-responsiveness was similar between the two species, but model simulations revealed that the dendrites could process ~6.5 times (n = 51 vs. n = 8) more input patterns in human Purkinje cells than in mouse Purkinje cells. Thus, while human Purkinje cells maintained spike discharge properties similar to those of rodents during evolution, they developed more complex dendrites, enhancing computational capacity.

Pautas de tratamiento para la infección tuberculosa latente / Treatment guidelines for latent tuberculous infection

Introducción: Los trabajadores de la salud tienen 2 veces más riesgo de padecer Tuberculosis (TB), teniendo un impacto en transmisión de nosocomial en los Centros Sanitarios (CS). Ello resalta el importante papel que desempeñan los Servicios de Prevención de Riesgos Laborales (SPRL). Objetivos: analizar las pautas de tratamiento para la infección tuberculosa latente en los últimos 5 años. Material y Método: Revisión sistemática en MEDLINE con bases de datos PUBMED, SCOPUS, EMBASE, WOS, Cochrane Library Plus, IBECS, LILACS y CISDOC. MeSH “Latent Tuberculosis Infection” y “Latent Tuberculosis/drug therapy”. Estándares de calidad: CONSORT y comprobación de evidencia: sistema SIGN. Resultados: se seleccionaron 5 ensayos clínicos (n= 14.931) que analizaron pautas cortas respecto a Isoniacida en monoterapia, con diferencias significativas a favor de las pautas cortas. Conclusiones: Las pautas cortas sugieren: menos efectos adversos, aumento en la adherencia y mayor tasa de finalización del tratamiento. (AU)

Introduction: Healthcare workers have twice the risk of suffering from tuberculosis. Which has an impact on nosocomial transmission in Health Care Centres (HCC). This highlights the important role played by Occupational Risk Prevention (ORP). Objectives: to analyse the treatment guidelines for latent tuberculosis infection in the last 5 years. Materials and Methods: Systematic review in MEDLINE with PUBMED, SCOPUS, EMBASE, WOS, Cochrane Library Plus, IBECS, LILACS and CISDOC databases. MeSH “Latent Tuberculosis Infection” and “Latent Tuberculosis/drug therapy”. Quality standards: CONSORT and evidence verification: SIGN system.Results: 5 clinical trials (n= 14,931) were selected that analysed short regimens compared to Isoniazid monotherapy, with significant differences in favour of short regimens. Conclusions: Short guidelines suggest, fewer adverse effects, increased adherence, and higher treatment completion rate. (AU)

Differential methylation pattern in pubertal girls associated with biochemical premature adrenarche.

Biochemical premature adrenarche is defined by elevated serum DHEAS [≥40 µg/dL] before age 8 y in girls. This condition is receiving more attention due to its association with obesity, hyperinsulinemia, dyslipidemia, and polycystic ovary syndrome. Nevertheless, the link between early androgen excess and these risk factors remains unknown. Epigenetic modifications, and specifically DNA methylation, have been associated with the initiation and progression of numerous disorders, including obesity and insulin resistance. The aim of this study was to determine if prepubertal androgen exposure is associated with a different methylation profile in pubertal girls. Eighty-six healthy girls were studied. At age 7 y, anthropometric measurements were begun and DHEAS levels were determined. Girls were classified into Low DHEAS (LD) [<42 µg/dL] and High DHEAS (HD) [≥42 µg/dL] groups. At Tanner stages 2 and 4 a DNA methylation microarray was performed to identify differentially methylated CpG positions (DMPs) between HD and LD groups. We observed a differential methylation pattern between pubertal girls with and without biochemical PA. Moreover, a set of DNA methylation markers, selected by the LASSO method, successfully distinguished between HD and LD girls regardless of Tanner stage. Additionally, a subset of these markers were significantly associated with glucose-related measures such as insulin level, HOMA-IR, and glycaemia. This pilot study provides evidence consistent with the hypothesis that high DHEAS concentration, or its hormonally active metabolites, may induce a unique blood methylation signature in pubertal girls, and that this methylation pattern is associated with altered glucose metabolism.

Dual Antiplatelet Therapy Versus Antiplatelet Monotherapy Plus Oral Anticoagulation in Patients with Acute Coronary Syndrome and Coronary Artery Ectasia: Design and Rationale of OVER-TIME Randomized Clinical Trial.

INTRODUCTION: The optimal anti-thrombotic therapy to prevent recurrent ischemic events in patients with acute coronary syndrome and coronary artery ectasia (CAE) remains unclear. AIM: To assess the efficacy and safety of antiplatelet plus anticoagulant therapy versus dual antiplatelet therapy in patients with acute coronary syndromes and coronary artery ectasia. METHODS: OVER-TIME is an investigator initiated, exploratory, open label, single center, randomized clinical trial comparing dual antiplatelet therapy (acetyl-salicylic acid plus a P2Y12 inhibitor) with the combination of an antiplatelet monotherapy (a P2Y12 inhibitor) plus a low dose anticoagulant (rivaroxaban, 15mg oral dose) for the prevention of recurrent ischemic events among patients with CAE. We aim to enroll approximately 60 patients with CAE and acute coronary syndromes. After recruitment, patients are randomized to (a) standard of care (dual antiplatelet regimen) or (b) the combination of antiplatelet monotherapy and low dose anticoagulant. Patients will be followed for at least 12 months. The OVER-TIME study aims to assess the efficacy of the regimen in prevention of major cardiovascular events and its security in bleeding events in acute coronary syndromes among patients with CAE. Expected results and conclusions: OVER-TIME is the first randomized controlled trial to assess different antithrombotic strategies in patients with CAE and acute coronary syndrome, and its results will offer preliminary data for the prevention of major cardiovascular events and bleeding events in this group of patients. TRIAL REGISTRATION NUMBER: NCT05233124 (ClinicalTrials.gov), date of registration: February 10, 2022.

Impact of Previous Coronavirus Disease 2019 on Immune Response After a Single Dose of BNT162b2 Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine.

Immune response after a single dose of BNT162b2 vaccine was markedly increased in subjects with previous severe acute respiratory syndrome coronavirus 2 infection, reaching similar immunoglobulin titers to those elicited by the full 2 doses in naive cases, and increased modestly after the second dose. These data may inform the priority of the boosting dose.

SARS-CoV-2 new infections among health-care workers after the first dose of the BNT162b2 mRNA COVID-19 vaccine. A hospital-wide cohort study.

OBJECTIVES: To evaluate the effect of mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination on the incidence of new SARS-CoV-2 infections in health-care workers (HCW). METHODS: The evolution of the incident rate of microbiologically confirmed SARS-CoV-2 infection in a cohort of 2590 HCW after BNT162b2 mRNA SARS-CoV-2 vaccination, compared with the rate in the community (n = 170 513) was evaluated by mixed Poisson regression models. RESULTS: A total of 1820 HCW (70.3% of total) received the first dose of the BNT162b2 mRNA vaccine between 10 January and 16 January 2021, and 296 (11.4%) received it the following week. All of them completed vaccination 3 weeks later. Incidence rates of SARS-CoV-2 infection after the first dose of mRNA SARS-CoV-2 vaccine declined by 71% (Incidence Rate Ratio (IRR) 0.286, 95% CI 0.174-0.468; p < 0.001) and by 97% (IRR 0.03, 95% CI 0.013-0.068; p < 0.001) after the second dose, compared with the perivaccine time. SARS-CoV-2 incidence rates in the community (with a negligible vaccination rate) had a much lower decline: 2% (IRR 0.984, 95% CI 0.943-1.028; p 0.47) and 61% (IRR 0.390, 95% CI 0.375-0.406; p < 0.001) for equivalent periods. Adjusting for the decline in the community, the reduction in the incident rates among HCW were 73% (IRR 0.272, 95% CI 0.164-0.451 p < 0.001) after the first dose of the vaccine and 92% (IRR 0.176, 95% CI 0.033-0.174; p < 0.001) after the second dose. CONCLUSIONS: mRNA SARS-CoV-2 vaccination is associated with a dramatic decline in new SARS-CoV-2 infection among HCW, even before the administration of the second dose of the vaccine.

Carcinoma bilateral de mama en crisis visceral / Bilateral breast carcinoma in visceral crisis

El carcinoma bilateral de mama es poco frecuente y raro, es bueno definir si ocurre de forma sincrónica o de forma metacrónica , definir si la lesión en la segunda mama es metástasis o un tumor primario usando criterios patológicos , el estadío y condición clínica . Ya que orienta en el pronóstico y tratamiento especializado a seguir. Presentamos el caso de una paciente con cáncer de mama ECIV por metástasis de mama contralateral en estado de crisis visceral al debut , con anatomía patológica de carcinoma ductal infiltrante de mama, grado 2, componente in situ ausente en ambas mama , RE(70%)RP(80%)Cerb2-,Ki67 30% en mama derecha y RE(100%)RP(80%)Cerb2-Ki67 20% en mama izquierda. Se realizó tomografía de tórax-abdomen-pelvis, evidenciándose derrame pleural bilateral y ascitis en gran volumen. Se decide iniciar tratamiento con quimioterapia sistémica alcanzándose respuesta completa radiológica y clínica. Tras conseguir buen control de la enfermedad se decidió iniciar primera línea hormonal.

Bilateral breast carcinoma is rare and infrequent , it is good to define if it occurs synchronously or metachronously, to define if the lesion in the second breast is metastasis or a primary tumor using pathological criteria, the state and clinical condition . For the prognosis and specialized treatment to follow. We present the case of a patient with ECIV breast cancer due to contralateral breast metastasis in a state of visceral crisis at debut, with pathological anatomy of grade 2 infiltrating ductal carcinoma of the breast, absent in situ component in both breast , RE (70%) , RP (80%), Cerb2 negative, Ki67 30% in the right breast and RE (100%) RP (80%) Cerb2-Ki67 20% left breast. A chest-abdomen-pelvis tomography was performed, showing pleural effusion. bilateral and large volume ascites. It was decided to start treatment with systemic chemotherapy, reaching a complete radiological and clinical response. After achieving good control of the disease, the first hormonal line will be sought.

Stellate cell computational modeling predicts signal filtering in the molecular layer circuit of cerebellum.

The functional properties of cerebellar stellate cells and the way they regulate molecular layer activity are still unclear. We have measured stellate cells electroresponsiveness and their activation by parallel fiber bursts. Stellate cells showed intrinsic pacemaking, along with characteristic responses to depolarization and hyperpolarization, and showed a marked short-term facilitation during repetitive parallel fiber transmission. Spikes were emitted after a lag and only at high frequency, making stellate cells to operate as delay-high-pass filters. A detailed computational model summarizing these physiological properties allowed to explore different functional configurations of the parallel fiber-stellate cell-Purkinje cell circuit. Simulations showed that, following parallel fiber stimulation, Purkinje cells almost linearly increased their response with input frequency, but such an increase was inhibited by stellate cells, which leveled the Purkinje cell gain curve to its 4 Hz value. When reciprocal inhibitory connections between stellate cells were activated, the control of stellate cells over Purkinje cell discharge was maintained only at very high frequencies. These simulations thus predict a new role for stellate cells, which could endow the molecular layer with low-pass and band-pass filtering properties regulating Purkinje cell gain and, along with this, also burst delay and the burst-pause responses pattern.

RAF1 variant in a patient with Noonan syndrome with multiple lentigines and craniosynostosis.

We report the case of a 14 years and 8 months girl, who is the first child of nonconsanguineous parents, with short stature, obstructive hypertrophic cardiomyopathy, multiple facial lentigines, high and wide forehead, downslanting palpebral fissures, low-set ears, short neck, and pectus excavatum; all features suggestive of Noonan syndrome with multiple lentigines (NSML). In addition, the patient exhibited craniosynostosis. Molecular analysis of rats sarcoma (RAS)/mitogen-activated protein kinase (MAPK) pathway genes with high-resolution melting curve analysis followed by sequencing showed a RAF1 amino acid substitution of valine to glycine at position 263 (p.V263G). The present report provides clinical data regarding the first association of a RAF1 variant and craniosynostosis in a patient with clinical diagnosis of NSML.

Co-occurrence of Noonan and Cardiofaciocutaneous Syndrome Features in a Patient with KRAS Variant.

We report the case of a 3-year-old girl, who is the third child of nonconsanguineous parents, with short stature, hypertrophic cardiomyopathy, and mild dysmorphic features; all suggestive of Noonan syndrome. In addition, the patient presents with feeding difficulties, deep palmar and plantar creases, sparse hair, and delayed psychomotor and language development, all characteristics frequently observed in cardiofaciocutaneous syndrome. Molecular analysis of the Ras/ MAPK pathway genes using high-resolution melting curve analysis and gene sequencing revealed a de novo KRAS amino acid substitution of leucine to tryptophan at codon 53 (p.L53W). This substitution was recently described in an Iranian patient with Noonan syndrome. The findings described in this report expand the phenotypic heterogeneity observed in RASopathy patients harboring a KRAS substitution, and advocate for the inclusion of genes with low mutational frequency in genetic screening protocols for Noonan syndrome and other RASopathies.

Miomectomía por laparoscopia con extracción por colpotomía posterior: reporte de tres casos / Laparoscopic myomectomy with extraction by posterior colpotomy: Report of three cases

Resumen ANTECEDENTES La extracción de un mioma, posterior a la resección laparoscópica, puede ser: directa, mediante colpotomía posterior, minilaparotomía, morcelación intraabdominal estándar o eléctrica. La mayor parte de estas opciones suele requerir la colocación de un trocar de 10-12 mm o la ampliación de la incisión en la piel y fascia para extraer el tejido; esto implica desventajas estéticas y clínicas, como el riesgo de hernias incisionales. CASOS CLÍNICOS Se comunican tres casos de pacientes con diagnóstico de miomatosis de grandes elementos (7 cm el menor y 15 cm el mayor) en los que posterior a la miomectomía por laparoscopia se extrae la pieza quirúrgica íntegra mediante colpotomía posterior, con evolución posquirúrgica favorable y sin síntomas concomitantes. CONCLUSIÓN La extracción transvaginal mediante colpotomía posterior es una alternativa segura y efectiva para retirar piezas quirúrgicas porque la elasticidad de la vagina permite extraer de forma segura piezas grandes, y evitar así el uso del morcelador y sus posibles riesgos. Además, se evita ampliar las incisiones abdominales, lo que implica menor dolor posoperatorio, recuperación más rápida y mejores resultados cosméticos. La vía vaginal es segura, con mínimo riesgo de complicaciones y con mejores resultados posquirúrgicos comparada con el resto de las opciones de cirugía laparoscópica.

Abstract BACKGROUND The extraction of the myoma after laparoscopic resection can be done by: direct extraction, standard intra-abdominal morcellation, electric morcellation, extraction by posterior colpotomy or by minilaparotomy. Most of these options generally require placement of a 10-12 mm trocar and / or enlargement of the skin incision and fascia for tissue removal; In addition to the aesthetic disadvantages, it represents clinical implications such as the risk of incisional hernias. CLINICAL CASES We present 3 cases of patients with diagnosis of myomatosis of large elements, the smallest being 7 cm and the largest being 15 cm, in greater diameter, after the laparoscopic myomectomy the extraction of the complete surgical piece is performed through posterior colpotomy, presenting a favorable postoperative recovery, without associated symptoms. CONCLUSIONS The transvaginal extraction through posterior colpotomy represents a safe and effective alternative for the extraction of surgical pieces, the elasticity of the vagina allows the safe extraction of large pieces, avoiding the use of the morcellator and its possible risks; It also avoids expanding the abdominal incisions, associating to less postoperative pain, faster recovery and better cosmetic results. The vaginal route is a safe option with minimal risk of complications, and with better postsurgical results compared to the other options in laparoscopic surgery.

Acretismo placentario con abordaje predictivo y preventivo de hemorragia obstétrica / Placental accreta with predictive and preventive approach to obstetric hemorrhage

Resumen OBJETIVO Exponer el tratamiento médico y quirúrgico indicado en el Hospital Universitario de Saltillo a pacientes con acretismo placentario. MATERIALES Y MÉTODOS Estudio retrospectivo, transversal y analítico efectuado en pacientes tratadas con enfoque predictivo y preventivo de hemorragia obstétrica atendidas entre los años 2015-2017. Se incluyeron todas las pacientes operadas con la técnica descrita. Se analizan las variables maternas y fetales posquirúrgicas que aportan información para evaluar los resultados obstétricos mediante medias y porcentajes. RESULTADOS Se incluyeron 10 pacientes con media de edad de 31 años, 70% con antecedente de cesárea y 50% de legrado. El sangrado transquirúrgico tuvo una media de 1067 cc, con un tiempo quirúrgico promedio de 3.6 h, la media de transfusión de concentrados eritrocitarios fue de 2.3, el Apgar de los recién nacidos se reportó en ≥ 7, no se requirió reinternvención y no se encontraron casos de muerte materna. CONCLUSIONES Si bien el tamaño de la muestra es pequeño continuaremos recabando datos de lo sucedido con otras pacientes. Es indispensable estudiar más casos para tener evidencias de nuestra propuesta de tratamiento con pruebas aún más sólidas. También hace falta un seguimiento prolongado a las pacientes para conocer si hay o no complicaciones tardías.

Abstract OBJECTIVE Expose the medical and surgical treatment indicated in the University Hospital of Saltillo to patients with placental accreta. MATERIAL AND METHODS A retrospective, cross-sectional and analytical study, patients treated with a predictive and preventive approach of obstetric hemorrhage were studied in Hospital Universitario de Saltillo during 2015-2017. RESULTS 10 patients were included, with a mean age of 31 years, 70% had a history of cesarean section and 50% curettage. Transurgical bleeding averaged 1067 cc, an average surgical time of 3.6 hrs, average of transfusion of erythrocyte concentrates was 2.3, Apgar of newborns was reported ≥7, no surgical reoperation was required, no cases were found of maternal death. CONCLUSIONS Although the size of the sample is small, we will continue to collect data on what happened with other patients. It is essential to study more cases to have evidence of our treatment proposal with even more solid evidence. There is also a need for prolonged follow-up of patients to determine whether there are late complications or not.

Exposición a pesticidas en el ámbito laboral, expresión genética y enfermedad de Parkinson / Pesticides Exposure at Workplace, Gene Expression and Parkinson’s disease

Introducción: Varias exposiciones ocupacionales pueden aumentar el riesgo de desarrollar la enfermedad de Parkinson. La exposición a pesticidas es un conocido factor de riesgo, pero no es suficiente para causar EP. Otros factores, como la susceptibilidad de diferentes variantes genéticas se cree son necesarias. Objetivo: Identificar la relación existente entre la exposición a pesticidas y la predisposición genética para la aparición de EP en el ámbito laboral. Concretar los genes y sus variables que pueden cambiar el riesgo de enfermar. Factores intrínsecos/extrínsecos que pueden influir en el desarrollo de EP. Actividades profesionales que incrementan el riego. Método: Revisión sistemática, realizada a través de búsqueda bibliográfica de artículos científicos publicados en los últimos 10 años en las siguientes bases de datos: MEDLINE (a través de Pubmed), LILACS, IBECS, Red SCIELO, BIBLIOTECA COCHRANE, utilizándose términos (MeSH terms). Se graduó el nivel de evidencia basado en los criterios SIGN. Resultados: Se recuperaron un total de 148 artículos. Después de aplicar los criterios de inclusión/ exclusión quedó una colección de 9. Todos fueron estudios de casos y controles, dos anidados en una cohorte. Los resultados obtenidos fueron estadísticamente significativos en relación a la variable estudiada. Conclusiones: En todos los artículos revisados se encontró asociación entre la variable genética estudiada, la exposición a pesticidas y el desarrollo de EP o descenso en la edad de aparición de EP con un alto nivel de evidencia (AU)

Introduction: Several occupational exposures may increase the risk of developing Parkinson’s disease. Exposure to pesticides is a known risk factor but is never enough to cause PD. Other factors, such as susceptibility of different genetic variants are believed to be necessary. Objective: To identify the scientific evidence between pesticides exposure and genetic predisposition for a PD outbreak at workplace. To specify genes and their variables that may change the risk of developing the disease. To identify intrinsic and extrinsic factors that influence Parkinson’s disease risk. To know the professional activities that may increase the risk. Method: Bibliographic search for systematic review in scientific articles published over the last 10 years in the following databases: MEDLINE (through Pubmed), LILACS, IBECS, SCIELO Network, COCHRANE LIBRARY, using terms (MeSH terms). Level of evidence was based on the SIGN criteria. Results: We retrieved 148 articles. 9 articles remained after applying the inclusion and exclusion criteria. The articles selected are case-control, two of them are case-control nested in a cohort. Results of all studies were statistically significant. Conclusions: An association between the genetic variable studied, pesticides exposure and the development of PD or a reduction of PD for all onset ages with a high level of evidence were found in all the articles reviewed (AU)

GSK3 and ß-catenin determines functional expression of sodium channels at the axon initial segment.

Neuronal action potentials are generated through voltage-gated sodium channels, which are tethered by ankyrinG at the membrane of the axon initial segment (AIS). Despite the importance of the AIS in the control of neuronal excitability, the cellular and molecular mechanisms regulating sodium channel expression at the AIS remain elusive. Our results show that GSK3α/ß and ß-catenin phosphorylated by GSK3 (S33/37/T41) are localized at the AIS and are new components of this essential neuronal domain. Pharmacological inhibition of GSK3 or ß-catenin knockdown with shRNAs decreased the levels of phosphorylated-ß-catenin, ankyrinG, and voltage-gated sodium channels at the AIS, both "in vitro" and "in vivo", therefore diminishing neuronal excitability as evaluated via sodium current amplitude and action potential number. Thus, our results suggest a mechanism for the modulation of neuronal excitability through the control of sodium channel density by GSK3 and ß-catenin at the AIS.

Developmental expression of Kv potassium channels at the axon initial segment of cultured hippocampal neurons.

Axonal outgrowth and the formation of the axon initial segment (AIS) are early events in the acquisition of neuronal polarity. The AIS is characterized by a high concentration of voltage-dependent sodium and potassium channels. However, the specific ion channel subunits present and their precise localization in this axonal subdomain vary both during development and among the types of neurons, probably determining their firing characteristics in response to stimulation. Here, we characterize the developmental expression of different subfamilies of voltage-gated potassium channels in the AISs of cultured mouse hippocampal neurons, including subunits Kv1.2, Kv2.2 and Kv7.2. In contrast to the early appearance of voltage-gated sodium channels and the Kv7.2 subunit at the AIS, Kv1.2 and Kv2.2 subunits were tethered at the AIS only after 10 days in vitro. Interestingly, we observed different patterns of Kv1.2 and Kv2.2 subunit expression, with each confined to distinct neuronal populations. The accumulation of Kv1.2 and Kv2.2 subunits at the AIS was dependent on ankyrin G tethering, it was not affected by disruption of the actin cytoskeleton and it was resistant to detergent extraction, as described previously for other AIS proteins. This distribution of potassium channels in the AIS further emphasizes the heterogeneity of this structure in different neuronal populations, as proposed previously, and suggests corresponding differences in action potential regulation.

Relationship between visual counts and call detection rates of gray whales (Eschrichtius robustus) in Laguna San Ignacio, Mexico.

Daily acoustic calling rates of Eastern North Pacific (ENP) gray whales were measured on 6 days during 1 mo of their 2008 breeding season in the sheltered coastal lagoon of Laguna San Ignacio in Baja California, Mexico. Visual counts of whales determined that the numbers of single animals in the lower lagoon more than tripled over the observation period. All call types showed production peaks in the early morning and evening with minimum rates generally detected in the early afternoon. For four of the five observation days, the daily number of "S1"-type calls increased roughly as the square of the number of the animals in the lower lagoon during both daytime and nighttime. This relationship persisted when raw call counts were adjusted for variations in background noise level, using a simple propagation law derived from empirical measurements. The one observation day that did not fit the square-law relationship occurred during a week when the group size in the lagoon increased rapidly. These results suggest that passive acoustic monitoring does not measure gray whale group size directly but monitors the number of connections in the social network, which rises as roughly M(2)/2 for a group size M.

Colocalization of α-actinin and synaptopodin in the pyramidal cell axon initial segment.

The cisternal organelle that resides in the axon initial segment (AIS) of neocortical and hippocampal pyramidal cells is thought to be involved in regulating the Ca(2+) available to maintain AIS scaffolding proteins, thereby preserving normal AIS structure and function. Through immunocytochemistry and correlative light and electron microscopy, we show here that the actin-binding protein α-actinin is present in the typical cistenal organelle of rodent pyramidal neurons as well as in a large structure in the AIS of a subpopulation of layer V pyramidal cells that we have called the "giant saccular organelle." Indeed, this localization of α-actinin in the AIS is dependent on the integrity of the actin cytoskeleton. Moreover, in the cisternal organelle of cultured hippocampal neurons, α-actinin colocalizes extensively with synaptopodin, a protein that interacts with both actin and α-actinin, and they appear concomitantly during the development of these neurons. Together, these results indicate that α-actinin and the actin cytoskeleton are important components of the cisternal organelle that are probably required to stabilize the AIS.