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Summary A fundamental aspect of epithelial homeostasis is the dependence on specific growth factors for cell survival, yet the underlying mechanisms remain obscure. We found an “inverse” mode of receptor tyrosine kinase signaling that directly links ErbB receptor inactivation to the induction of apoptosis. Upon ligand deprivation Mig6 dissociates from the ErbB receptor and binds to and activates the tyrosine kinase c-Abl to trigger p73-dependent apoptosis in mammary epithelial cells. Deletion of Errfi1 (encoding Mig6) and inhibition or RNAi silencing of c-Abl causes impaired apoptosis and luminal filling of mammary ducts. Mig6 activates c-Abl by binding to the kinase domain, which is prevented in the presence of epidermal growth factor (EGF) by Src family kinase-mediated phosphorylation on c-Abl-Tyr488. These results reveal a receptor-proximal switch mechanism by which Mig6 actively senses EGF deprivation to directly activate proapoptotic c-Abl. Our findings challenge the common belief that deprivation of growth factors induces apoptosis passively by lack of mitogenic signaling., Graphical Abstract Highlights ► EGFR inactivation triggers “inverse signaling” by Mig6-mediated activation of Abl ► Mig6 is a bimodal switch that attenuates EGFR (+EGF) or activates c-Abl (-EGF) ► Mig6 activation of Abl regulates cell death during mammary epithelial homeostasis, Hopkins et al. show that tyrosine kinase signaling directly links EGF receptor (ErbB) inactivation to the induction of apoptosis. Inactivation dissociates ErbBs from the Mig6 tumor suppressor, which then binds and activates c-Abl to trigger p73-dependent apoptosis. This mechanism controls mammary epithelial homeostasis and may also contribute to oncogene addiction.

Organisation is a key factor for successful everyday adaptive functioning in schools. Although it is widely recognised that the school environment requires students to be organised if they are to be successful, particularly at the secondary school level, there is currently a lack of instruments available for measuring this construct. To address this, a new teacher report measure of student disorganisation behaviours in the secondary school environment was developed. Following a review of the literature and currently available instrumentation, three phases were implemented: focus-group interviews with primary and secondary teachers; a pilot test of the newly developed instrument to check face validity and item functioning; and an analysis of data from a large scale administration based on the Rasch measurement model. The outcome was a 23-item teacher report scale entitled the Student Disorganisation Scale.

Although an increasing proportion of the US population receives health services through managed care, pregnant women and mothers eligible for Medicaid who are involved with alcohol or other drugs are often excluded from these programs due in large part to lack of information on costs, service needs, and service use. To develop such information policy, service settings, and managed-care plans, the project conducted a national survey using a provider group with experience in caring for this population, the member universe of the National Association of Public Hospitals and Health Systems. The survey requested detailed information on hospital system information, current managed-care arrangements, outcome measurements, financing, service priorities, and service availability. The 81% response rate (n = 95) identified 35 hospital systems providing services to an average of 998 women in 1997. The majority of these systems (69%) reported coordinating care for these patients, but only 26% reported they computerize patient charts. Most use at least one indicator to measure effectiveness, and 50% use at least four. Counseling/education and transportation were seen as key support services, but many acknowledge they are not reimbursed for critical services such as nutrition education. The discussion highlights the need to provide formal support for core support services, to assist in care coordination and provide incentives for developing more sophisticated information, and to specify related services in the state Medicaid contract language.

A 34-year-old woman with a history of relapsing psychosis presented with a 15-month history of impassivity and social withdrawal associated with cognitive impairment. The subsequent recurrence of psychomotor agitation, auditory hallucinations and delusional thinking resulted in an emergency admission under psychiatric services. Initial investigations, including MRI of the brain and cerebrospinal fluid studies were unremarkable and she was treated for a primary psychiatric disorder. The diagnosis of autoimmune limbic encephalitis was established after further investigations revealed the presence of antibodies to the NR1 subunit of the N-Methyl-d-aspartate receptor (NMDAR). Immunotherapy resulted in rapid resolution of psychosis and marked improvement in cognitive and social function. This case underlines the importance of considering anti-NMDAR encephalitis within the differential diagnosis of psychosis associated with cognitive impairment even in those with an apparent previous psychiatric history and response to antipsychotics.

A fundamental goal of Earth science is to understand the remarkable instability of late Quaternary global climate prior to the beginning of the Holocene, about 11,000 years ago. This unusual climate behavior was characterized by millennial-scale climate oscillations on suborbital timescales, and a distinctive ‘sawtooth’ pattern of very abrupt glacial and stadial terminations (within decades) followed by more gradual global cooling [e.g., Dansgaard et al., 1993; Hendy and Kennett, 1999]. The fact that both major (glacial) and minor (stadial) cooling periods in Earth's climate were terminated by similar abrupt warming episodes suggests a common mechanism driving such rapid changes in global climate. Understanding the causes of this instability is crucial given developing concerns about global warming, yet knowledge about this climate behavior has been essentially confined to the last 150,000 years or so, owing to the absence of available sequences of sufficient age and chronological resolution. The high-resolution paleoclimate record from the Greenland ice cores is limited to about 110 thousand years ago (ka),and although Antarctic ice cores now extend back to more than 740 ka [European Project for Ice Coring in Antarctica, 2004], these latter cores primarily provide information about high-latitude conditions at much lower resolution than is required to address abrupt climate change.

"Stereotyped by Thomas B. Smith, 216 William St., N.Y."--verso of title page., Added title page, engraved., Wood-engravings variously signed: Howland; R. Austin; & W. Roberts., "Cousin Cicely's Silver Lake stories."--illustrated series title, p. [3]. Series list, p. [8]., Electronic reproduction. [Florida] : Florida Board of Education, Division of Colleges and Universities, PALMM Project, 2001. (Preservation and Access for American and British Children's Literature, 1850-1869 (NEH PA-23536-00) ) Mode of access: World Wide Web. System requirements: Internet connectivity; Web browser software; Adobe Acrobat Reader to view and print PDF files. Electronically reproduced from collection in the George A. Smathers Libraries of the University of Florida.

Ill. engraved by Howland, W. Roberts and Lossing-Barritt., Electronic reproduction. [Florida] : Florida Board of Education, Division of Colleges and Universities, PALMM Project, 2001. Preservation and Access for American and British Children's Literature, 1850-1869 (NEH PA-23536-00)) Mode of access: World Wide Web. System requirements: Internet connectivity; Web browser software; Adobe Acrobat Reader to view and print PDF files. Electronically reproduced from collection in the George A. Smathers Libraries of the University of Florida., Aunt Patty's mirror, Silver Lake stories

Background Bartonella species comprise a group of zoonotic pathogens that are usually acquired by vector transmission or by animal bites or scratches. Methods PCR targeting the Bartonella 16S-23S intergenic spacer (ITS) region was used in conjunction with BAPGM (Bartonella alpha Proteobacteria growth medium) enrichment blood culture to determine the infection status of the family members and to amplify DNA from spiders and woodlice. Antibody titers to B. vinsonii subsp. berkhoffii (Bvb) genotypes I-III, B. henselae (Bh) and B. koehlerae (Bk) were determined using an IFA test. Management of the medical problems reported by these patients was provided by their respective physicians. Results In this investigation, immediately prior to the onset of symptoms two children in a family experienced puncture-like skin lesions after exposure to and presumptive bites from woodlouse hunter spiders. Shortly thereafter, the mother and both children developed hive-like lesions. Over the ensuing months, the youngest son was diagnosed with Guillain-Barre (GBS) syndrome followed by Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP). The older son developed intermittent disorientation and irritability, and the mother experienced fatigue, headaches, joint pain and memory loss. When tested approximately three years after the woodlouse hunter spider infestation, all three family members were Bartonella henselae seroreactive and B. henselae DNA was amplified and sequenced from blood, serum or Bartonella alpha-proteobacteria (BAPGM) enrichment blood cultures from the mother and oldest son. Also, B. henselae DNA was PCR amplified and sequenced from a woodlouse and from woodlouse hunter spiders collected adjacent to the family’s home. Conclusions Although it was not possible to determine whether the family’s B. henselae infections were acquired by spider bites or whether the spiders and woodlice were merely accidental hosts, physicians should consider the possibility that B. henselae represents an antecedent infection for GBS, CIDP, and non-specific neurocognitive abnormalities.