Molecular basis for passive immunotherapy of Alzheimer's disease

Amyloid aggregates of the amyloid-{beta} (A{beta}) peptide are implicated in the pathology of Alzheimer's disease. Anti-A{beta} monoclonal antibodies (mAbs) have been shown to reduce amyloid plaques in vitro and in animal studies. Consequently, passive immunization is being considered for treating Alzheimer's, and anti-A{beta} mAbs are now in phase II trials. We report the isolation of two mAbs (PFA1 and PFA2) that recognize A{beta} monomers, protofibrils, and fibrils and the structures of their antigen binding fragments (Fabs) in complex with the A{beta}(1–8) peptide DAEFRHDS. The immunodominant EFRHD sequence forms salt bridges, hydrogen bonds, and hydrophobic contacts, including interactions with a striking WWDDD motif of the antigen binding fragments. We also show that a similar sequence (AKFRHD) derived from the human protein GRIP1 is able to cross-react with both PFA1 and PFA2 and, when cocrystallized with PFA1, binds in an identical conformation to A{beta}(1–8). Because such cross-reactivity has implications for potential side effects of immunotherapy, our structures provide a template for designing derivative mAbs that target A{beta} with improved specificity and higher affinity

Physician reported perception in the treatment of high blood pressure does not correspond to practice

<p>Abstract</p> <p>Background</p> <p>High blood pressure is a significant health problem world-wide. Physician factors play a significant role in the suboptimal control of hypertension in the United States. We sought to better understand primary care physician's opinions regarding use of hypertension guidelines, patient and physician related barriers to treatment and physician treatment decision making in the management of hypertension as part of a first step in developing research tools and interventions designed to address these issues.</p> <p>Methods</p> <p>An IRB approved survey pertaining to physician opinion regarding the treatment of hypertension. Items consisted of questions regarding: 1) knowledge of hypertension treatment guidelines; 2) barriers to hypertension control (physician vs. patient); and 3) self-estimation of physician treatment of hypertension. Descriptive Statistics were used to describe results.</p> <p>Results</p> <p>All physicians were board certified in family or general internal medicine (n = 28). Practices were located in urban (n = 12), suburban (n = 14) and inner city locations (n = 1). All physicians felt they did a good job of treating hypertension. Most physicians felt the biggest barrier to hypertension control was patient non-compliance. Half of physicians would fail to intensify treatment for hypertension when blood pressure was above recommended levels for all disease states studied (essential hypertension, heart disease, diabetes, and renal disease).</p> <p>Conclusion</p> <p>Physician ability to assess personal performance in the treatment of hypertension and physician opinion that patient noncompliance is the greatest barrier to optimal hypertension control is contradictory to reported practice behavior. Optimal blood pressure control requires increased physician understanding on the evaluation and management of blood pressure. These data provide crucial formative data to enhance the content validity of physician education efforts currently underway to improve the treatment of blood pressure in the primary care setting.</p

Silent Trace Eliminates Differential Eyeblink Learning in Abstinent Alcoholics

Chronic alcoholism has profound effects on the brain, including volume reductions in regions critical for eyeblink classical conditioning (EBCC). The current study challenged abstinent alcoholics using delay (n = 20) and trace (n = 17) discrimination/reversal EBCC. Comparisons revealed a significant difference between delay and trace conditioning performance during reversal (t (35) = 2.08, p < 0.05). The difference between the two tasks for discrimination was not significant (p = 0.44). These data support the notion that alcoholics are increasingly impaired in the complex task of reversing a previously learned discrimination when a silent trace interval is introduced. Alcoholics’ impairment in flexibly altering learned associations may be central to their continued addiction

A planned, prospective comparison of short-term quality of life outcomes among older patients with breast cancer treated with standard chemotherapy in a randomized clinical trial vs. an observational study: CALGB #49907 and #369901

Patients ≥65 years old (“older”) are often not included in randomized clinical trials (RCT), but when they are, care in an RCT might improve quality of life (QoL). We conducted a prospective comparison of QoL among older women receiving standard chemotherapy from the same cooperative group physicians in an RCT vs. an observational study (“off-trial”)

African linguistics across the disciplines: Selected papers from the 48th Annual Conference on African Linguistics

Since the hiring of its first Africanist linguist Carleton Hodge in 1964, Indiana University’s Department of Linguistics has had a strong and continuing presence in the study of African languages and linguistics through the work of its faculty and of its graduates on the faculties of many other universities. Research on African linguistics at IU has covered some of the major language groups spoken on the African continent. Carleton Hodge’s work on Ancient Egyptian and Hausa, Paul Newman’s work on Hausa and Chadic languages, and Roxanna Ma Newman’s work on Hausa language structure and pedagogy have been some of the most important studies on Afro-Asiatic linguistics. With respect to Niger-Congo languages, the work of Charles Bird on Bambara and the Mande languages, Robert Botne’s work on Bantu structure (especially tense and aspect), Samuel Obeng and Colin Painter’s work on Ghanaian Languages (phonetics, phonology, and pragmatics), Robert Port’s studies on Swahili, and Erhard Voeltz's studies on Bantu linguistics are considered some of the most influential studies in the sub-field. On Nilo Saharan languages, the work of Tim Shopen on Songhay stands out. IU Linguistics has also forwarded theoretical work on African languages, such as John Goldsmith’s seminal research on tone in African languages. The African linguistics faculty at IU have either founded or edited important journals in African Studies, African languages, and African linguistics, including Africa Today, Studies in African Linguistics, and Journal of African Languages and Linguistics. In 1972, the Indiana University Department of Linguistics hosted the Third Annual Conference of African Linguistics. Proceedings of that conference were published by Indiana University Publications (African Series, vol. 7). In 1986, IU hosted the Seventeenth Annual Conference of African Linguistics with Paul Newman and Robert Botne editing the proceedings in a volume entitled Current Approaches to African Linguistics, vol. 5. In 2016, Indiana University hosted the 48th Annual Conference on African Linguistics with the theme African Linguistics Across the Disciplines. Proceedings of that meeting are published in this volume. The papers presented in this volume reflect the diversity of opportunities for language study in Africa. This collection of descriptive and theoretical work is the fruit of data gathering both in-country and abroad by researchers of languages spoken across the continent, from Sereer-sin in the west to Somali in the northeast to Ikalanga in the south. The range of topics in this volume is also broad, representative of the varied field work in country and abroad that inspires research in African linguistics. This collection of papers spans the disciplines of phonology (both segmental and suprasegmental), morphology (both morphophonological and morphosyntactic), syntax, semantics, and language policy. The data and analyses presented in this volume offer a cross-disciplinary view of linguistic topics from the many under-resourced languages of Africa

African linguistics across the disciplines: Selected papers from the 48th Annual Conference on African Linguistics

Since the hiring of its first Africanist linguist Carleton Hodge in 1964, Indiana University’s Department of Linguistics has had a strong and continuing presence in the study of African languages and linguistics through the work of its faculty and of its graduates on the faculties of many other universities. Research on African linguistics at IU has covered some of the major language groups spoken on the African continent. Carleton Hodge’s work on Ancient Egyptian and Hausa, Paul Newman’s work on Hausa and Chadic languages, and Roxanna Ma Newman’s work on Hausa language structure and pedagogy have been some of the most important studies on Afro-Asiatic linguistics. With respect to Niger-Congo languages, the work of Charles Bird on Bambara and the Mande languages, Robert Botne’s work on Bantu structure (especially tense and aspect), Samuel Obeng and Colin Painter’s work on Ghanaian Languages (phonetics, phonology, and pragmatics), Robert Port’s studies on Swahili, and Erhard Voeltz's studies on Bantu linguistics are considered some of the most influential studies in the sub-field. On Nilo Saharan languages, the work of Tim Shopen on Songhay stands out. IU Linguistics has also forwarded theoretical work on African languages, such as John Goldsmith’s seminal research on tone in African languages. The African linguistics faculty at IU have either founded or edited important journals in African Studies, African languages, and African linguistics, including Africa Today, Studies in African Linguistics, and Journal of African Languages and Linguistics. In 1972, the Indiana University Department of Linguistics hosted the Third Annual Conference of African Linguistics. Proceedings of that conference were published by Indiana University Publications (African Series, vol. 7). In 1986, IU hosted the Seventeenth Annual Conference of African Linguistics with Paul Newman and Robert Botne editing the proceedings in a volume entitled Current Approaches to African Linguistics, vol. 5. In 2016, Indiana University hosted the 48th Annual Conference on African Linguistics with the theme African Linguistics Across the Disciplines. Proceedings of that meeting are published in this volume. The papers presented in this volume reflect the diversity of opportunities for language study in Africa. This collection of descriptive and theoretical work is the fruit of data gathering both in-country and abroad by researchers of languages spoken across the continent, from Sereer-sin in the west to Somali in the northeast to Ikalanga in the south. The range of topics in this volume is also broad, representative of the varied field work in country and abroad that inspires research in African linguistics. This collection of papers spans the disciplines of phonology (both segmental and suprasegmental), morphology (both morphophonological and morphosyntactic), syntax, semantics, and language policy. The data and analyses presented in this volume offer a cross-disciplinary view of linguistic topics from the many under-resourced languages of Africa

African linguistics across the disciplines: Selected papers from the 48th Annual Conference on African Linguistics

Since the hiring of its first Africanist linguist Carleton Hodge in 1964, Indiana University’s Department of Linguistics has had a strong and continuing presence in the study of African languages and linguistics through the work of its faculty and of its graduates on the faculties of many other universities. Research on African linguistics at IU has covered some of the major language groups spoken on the African continent. Carleton Hodge’s work on Ancient Egyptian and Hausa, Paul Newman’s work on Hausa and Chadic languages, and Roxanna Ma Newman’s work on Hausa language structure and pedagogy have been some of the most important studies on Afro-Asiatic linguistics. With respect to Niger-Congo languages, the work of Charles Bird on Bambara and the Mande languages, Robert Botne’s work on Bantu structure (especially tense and aspect), Samuel Obeng and Colin Painter’s work on Ghanaian Languages (phonetics, phonology, and pragmatics), Robert Port’s studies on Swahili, and Erhard Voeltz's studies on Bantu linguistics are considered some of the most influential studies in the sub-field. On Nilo Saharan languages, the work of Tim Shopen on Songhay stands out. IU Linguistics has also forwarded theoretical work on African languages, such as John Goldsmith’s seminal research on tone in African languages. The African linguistics faculty at IU have either founded or edited important journals in African Studies, African languages, and African linguistics, including Africa Today, Studies in African Linguistics, and Journal of African Languages and Linguistics. In 1972, the Indiana University Department of Linguistics hosted the Third Annual Conference of African Linguistics. Proceedings of that conference were published by Indiana University Publications (African Series, vol. 7). In 1986, IU hosted the Seventeenth Annual Conference of African Linguistics with Paul Newman and Robert Botne editing the proceedings in a volume entitled Current Approaches to African Linguistics, vol. 5. In 2016, Indiana University hosted the 48th Annual Conference on African Linguistics with the theme African Linguistics Across the Disciplines. Proceedings of that meeting are published in this volume. The papers presented in this volume reflect the diversity of opportunities for language study in Africa. This collection of descriptive and theoretical work is the fruit of data gathering both in-country and abroad by researchers of languages spoken across the continent, from Sereer-sin in the west to Somali in the northeast to Ikalanga in the south. The range of topics in this volume is also broad, representative of the varied field work in country and abroad that inspires research in African linguistics. This collection of papers spans the disciplines of phonology (both segmental and suprasegmental), morphology (both morphophonological and morphosyntactic), syntax, semantics, and language policy. The data and analyses presented in this volume offer a cross-disciplinary view of linguistic topics from the many under-resourced languages of Africa

African linguistics across the disciplines: Selected papers from the 48th Annual Conference on African Linguistics

Since the hiring of its first Africanist linguist Carleton Hodge in 1964, Indiana University’s Department of Linguistics has had a strong and continuing presence in the study of African languages and linguistics through the work of its faculty and of its graduates on the faculties of many other universities. Research on African linguistics at IU has covered some of the major language groups spoken on the African continent. Carleton Hodge’s work on Ancient Egyptian and Hausa, Paul Newman’s work on Hausa and Chadic languages, and Roxanna Ma Newman’s work on Hausa language structure and pedagogy have been some of the most important studies on Afro-Asiatic linguistics. With respect to Niger-Congo languages, the work of Charles Bird on Bambara and the Mande languages, Robert Botne’s work on Bantu structure (especially tense and aspect), Samuel Obeng and Colin Painter’s work on Ghanaian Languages (phonetics, phonology, and pragmatics), Robert Port’s studies on Swahili, and Erhard Voeltz's studies on Bantu linguistics are considered some of the most influential studies in the sub-field. On Nilo Saharan languages, the work of Tim Shopen on Songhay stands out. IU Linguistics has also forwarded theoretical work on African languages, such as John Goldsmith’s seminal research on tone in African languages. The African linguistics faculty at IU have either founded or edited important journals in African Studies, African languages, and African linguistics, including Africa Today, Studies in African Linguistics, and Journal of African Languages and Linguistics. In 1972, the Indiana University Department of Linguistics hosted the Third Annual Conference of African Linguistics. Proceedings of that conference were published by Indiana University Publications (African Series, vol. 7). In 1986, IU hosted the Seventeenth Annual Conference of African Linguistics with Paul Newman and Robert Botne editing the proceedings in a volume entitled Current Approaches to African Linguistics, vol. 5. In 2016, Indiana University hosted the 48th Annual Conference on African Linguistics with the theme African Linguistics Across the Disciplines. Proceedings of that meeting are published in this volume. The papers presented in this volume reflect the diversity of opportunities for language study in Africa. This collection of descriptive and theoretical work is the fruit of data gathering both in-country and abroad by researchers of languages spoken across the continent, from Sereer-sin in the west to Somali in the northeast to Ikalanga in the south. The range of topics in this volume is also broad, representative of the varied field work in country and abroad that inspires research in African linguistics. This collection of papers spans the disciplines of phonology (both segmental and suprasegmental), morphology (both morphophonological and morphosyntactic), syntax, semantics, and language policy. The data and analyses presented in this volume offer a cross-disciplinary view of linguistic topics from the many under-resourced languages of Africa