Interleukin-6 Interweaves the Bone Marrow Microenvironment, Bone Loss, and Multiple Myeloma

The immune system is strongly linked to the maintenance of healthy bone. Inflammatory cytokines, specifically, are crucial to skeletal homeostasis and any dysregulation can result in detrimental health complications. Interleukins, such as interleukin 6 (IL-6), act as osteoclast differentiation modulators and as such, must be carefully monitored and regulated. IL-6 encourages osteoclastogenesis when bound to progenitors and can cause excessive osteoclastic activity and osteolysis when overly abundant. Numerous bone diseases are tied to IL-6 overexpression, including rheumatoid arthritis, osteoporosis, and bone-metastatic cancers. In the latter, IL-6 can be released with growth factors into the bone marrow microenvironment (BMM) during osteolysis from bone matrix or from cancer cells and osteoblasts in an inflammatory response to cancer cells. Thus, IL-6 helps create an ideal microenvironment for oncogenesis and metastasis. Multiple myeloma (MM) is a blood cancer that homes to the BMM and is strongly tied to overexpression of IL-6 and bone loss. The roles of IL-6 in the progression of MM are discussed in this review, including roles in bone homing, cancer-associated bone loss, disease progression and drug resistance. MM disease progression often includes the development of drug-resistant clones, and patients commonly struggle with reoccurrence. As such, therapeutics that specifically target the microenvironment, rather than the cancer itself, are ideal and IL-6, and its myriad of downstream signaling partners, are model targets. Lastly, current and potential therapeutic interventions involving IL-6 and connected signaling molecules are discussed in this review

Middle and Late Pleistocene environmental history of the Marsworth area, south-central England

To elucidate the Middle and Late Pleistocene environmental history of south-central England, we report the stratigraphy, sedimentology, palaeoecology and geochronology of some deposits near the foot of the Chiltern Hills scarp at Marsworth, Buckinghamshire. The Marsworth site is important because its sedimentary sequences contain a rich record of warm stages and cold stages, and it lies close to the Anglian glacial limit. Critical to its history are the origin and age of a brown pebbly silty clay (diamicton) previously interpreted as weathered till. The deposits described infill a river channel incised into chalk bedrock. They comprise clayey, silty and gravelly sediments, many containing locally derived chalk and some with molluscan, ostracod and vertebrate remains. Most of the deposits are readily attributed to periglacial and fluvial processes, and some are dated by optically stimulated luminescence to Marine Isotope Stage (MIS) 6. Although our sedimentological data do not discriminate between a glacial or periglacial interpretation of the diamicton, amino-acid dating of three molluscan taxa from beneath it indicates that it is younger than MIS 9 and older than MIS 5e. This makes a glacial interpretation unlikely, and we interpret the diamicton as a periglacial slope deposit. The Pleistocene history reconstructed for Marsworth identifies four key elements: (1) Anglian glaciation during MIS 12 closely approached Marsworth, introducing far-travelled pebbles such as Rhaxella chert and possibly some fine sand minerals into the area. (2) Interglacial environments inferred from fluvial sediments during MIS 7 varied from fully interglacial conditions during sub-stages 7e and 7c, cool temperate conditions during sub-stage 7b or 7a, temperate conditions similar to those today in central England towards the end of the interglacial, and cool temperate conditions during sub-stage 7a. (3) Periglacial activity during MIS 6 involved thermal contraction cracking, permafrost development, fracturing of chalk bedrock, fluvial activity, slopewash, mass movement and deposition of loess and coversand. (4) Fully interglacial conditions during sub-stage 5e led to renewed fluvial activity, soil formation and acidic weathering

Catechol O-methyl transferase and dopamine D2 receptor gene polymorphisms: evidence of positive heterosis and gene–gene interaction on working memory functioning.

The COMT Va

Interleukin-6 Interweaves the Bone Marrow Microenvironment, Bone Loss, and Multiple Myeloma.

The immune system is strongly linked to the maintenance of healthy bone. Inflammatory cytokines, specifically, are crucial to skeletal homeostasis and any dysregulation can result in detrimental health complications. Interleukins, such as interleukin 6 (IL-6), act as osteoclast differentiation modulators and as such, must be carefully monitored and regulated. IL-6 encourages osteoclastogenesis when bound to progenitors and can cause excessive osteoclastic activity and osteolysis when overly abundant. Numerous bone diseases are tied to IL-6 overexpression, including rheumatoid arthritis, osteoporosis, and bone-metastatic cancers. In the latter, IL-6 can be released with growth factors into the bone marrow microenvironment (BMM) during osteolysis from bone matrix or from cancer cells and osteoblasts in an inflammatory response to cancer cells. Thus, IL-6 helps create an ideal microenvironment for oncogenesis and metastasis. Multiple myeloma (MM) is a blood cancer that homes to the BMM and is strongly tied to overexpression of IL-6 and bone loss. The roles of IL-6 in the progression of MM are discussed in this review, including roles in bone homing, cancer-associated bone loss, disease progression and drug resistance. MM disease progression often includes the development of drug-resistant clones, and patients commonly struggle with reoccurrence. As such, therapeutics that specifically target the microenvironment, rather than the cancer itself, are ideal and IL-6, and its myriad of downstream signaling partners, are model targets. Lastly, current and potential therapeutic interventions involving IL-6 and connected signaling molecules are discussed in this review

Interleukin-6 Interweaves the Bone Marrow Microenvironment, Bone Loss, and Multiple Myeloma

The immune system is strongly linked to the maintenance of healthy bone. Inflammatory cytokines, specifically, are crucial to skeletal homeostasis and any dysregulation can result in detrimental health complications. Interleukins, such as interleukin 6 (IL-6), act as osteoclast differentiation modulators and as such, must be carefully monitored and regulated. IL-6 encourages osteoclastogenesis when bound to progenitors and can cause excessive osteoclastic activity and osteolysis when overly abundant. Numerous bone diseases are tied to IL-6 overexpression, including rheumatoid arthritis, osteoporosis, and bone-metastatic cancers. In the latter, IL-6 can be released with growth factors into the bone marrow microenvironment (BMM) during osteolysis from bone matrix or from cancer cells and osteoblasts in an inflammatory response to cancer cells. Thus, IL-6 helps create an ideal microenvironment for oncogenesis and metastasis. Multiple myeloma (MM) is a blood cancer that homes to the BMM and is strongly tied to overexpression of IL-6 and bone loss. The roles of IL-6 in the progression of MM are discussed in this review, including roles in bone homing, cancer-associated bone loss, disease progression and drug resistance. MM disease progression often includes the development of drug-resistant clones, and patients commonly struggle with reoccurrence. As such, therapeutics that specifically target the microenvironment, rather than the cancer itself, are ideal and IL-6, and its myriad of downstream signaling partners, are model targets. Lastly, current and potential therapeutic interventions involving IL-6 and connected signaling molecules are discussed in this review

A Film Professor, A Biology Professor, and a Librarian Walk into a Learning Community

In this panel a film professor, a biology professor, and an academic librarian teaching a first-year seminar course will discuss how they built an interdisciplinary learning community for first-year students at a public four-year college. The three of us realized that our students were struggling to develop their information literacy skills and understandings in the first year of college. We knew we needed to design and offer courses that acknowledge that first-year college students are novice researchers who struggle with the research process and that recognize that these students need scaffolded and intentional guidance and support if they are to engage with the interconnected concepts, knowledge practices, and dispositions that define information literacy. Our interconnected courses and integrated assignments create the opportunities and structures our first-year students need to develop the information literacy strategies and dispositions that are fundamental to lifelong learning and productive global citizenship. We will talk about our design process, including how we worked to align our student learning goals and outcomes and course schedules, how we developed our integrated assignments and activities, and our challenges and successes in implementing this work. There will be ample time for questions and discussion with panel speakers and participants

A Film Professor, A Biology Professor, and a Librarian Walk into a Learning Community

In this panel a film professor, a biology professor, and an academic librarian teaching a first-year seminar course will discuss how they built an interdisciplinary learning community for first-year students at a public four-year college. The three of us realized that our students were struggling to develop their information literacy skills and understandings in the first year of college. We knew we needed to design and offer courses that acknowledge that first-year college students are novice researchers who struggle with the research process and that recognize that these students need scaffolded and intentional guidance and support if they are to engage with the interconnected concepts, knowledge practices, and dispositions that define information literacy. Our interconnected courses and integrated assignments create the opportunities and structures our first-year students need to develop the information literacy strategies and dispositions that are fundamental to lifelong learning and productive global citizenship. We will talk about our design process, including how we worked to align our student learning goals and outcomes and course schedules, how we developed our integrated assignments and activities, and our challenges and successes in implementing this work. There will be ample time for questions and discussion with panel speakers and participants

Stability, reliability, and validity of the THINC-it screening tool for cognitive impairment in depression: A psychometric exploration in healthy volunteers

Objectives: There is a need for a brief, reliable, valid, and sensitive assessment tool for screening cognitive deficits in patients with Major Depressive Disorders. This paper examines the psychometric characteristics of THINC-it, a cognitive assessment tool composed of four objective measures of cognition and a self-rated assessment, in subjects without mental disorders. Methods: N = 100 healthy controls with no current or past history of depression were tested on four sequential assessments to examine temporal stability, reliability, and convergent validity of the THINC-it tests. We examined temporal reliability across 1 week and stability via three consecutive assessments. Consistency of assessment by the study rater (intrarater reliability) was calculated using the data from the second and third of these consecutive assessments. Results: Test–retest reliability correlations varied between Pearson's r = 0.75 and 0.8. Intrarater reliability between 0.7 and 0.93. Stability for the primary measure for each test yielded within-subject standard deviation values between 5.9 and 11.23 for accuracy measures and 0.735 and 17.3 seconds for latency measures. Convergent validity for three tasks was in the acceptable range, but low for the Symbol Check task. Conclusions: Analysis shows high levels of reliability and stability. Levels of convergent validity were modest but acceptable in the case of all but one test