Search

Adipose tissue is a dynamic component of the bone marrow, regulating skeletal remodelling and secreting paracrine and endocrine factors that can affect haematopoiesis, as well as potentially nourishing the bone marrow during periods of stress. Bone marrow adipose tissue is regulated by multiple factors, but particularly nutrient status. In this Review, we examine how bone marrow adipocytes originate, their function in normal and pathological states and how bone marrow adipose tissue modulates whole-body homoeostasis through actions on bone cells, haematopoietic stem cells and extra-medullary adipocytes during nutritional challenges. We focus on both rodent models and human studies to help understand the unique marrow adipocyte, its response to the external nutrient environment and its effects on the skeleton. We finish by addressing some critical questions that to date remain unanswered. This Review examines the origins of marrow adipocytes and their function under normal or pathological conditions. Regulation of bone marrow adipose tissue by nutrient status is considered, as well as the interactions between bone marrow adipose tissue, haematopoietic cells of the bone marrow and the bone. Key points: Adipocytes are critical cellular components of the bone marrow that are regulated by local and systemic factors. Bone marrow adipocytes have unique origins and distinct functions that are distinguishable from extra-medullary adipocytes. In mice and humans, both axial and appendicular bone marrow adipose tissue increase with age and in response to environmental, nutritional and endocrine factors. Both a high-fat diet and caloric restriction enhance the recruitment and differentiation of marrow adipocytes, although their function might differ by nutrient stores. A unique marrow adipocyte-like precursor probably serves as a source of mature bone marrow adipocytes. Increased bone marrow adipose tissue can drive bone loss during high dietary intake or can protect the skeleton during caloric restriction. [ABSTRACT FROM AUTHOR]

Adaptation of the brain to the presence of a drug predicts withdrawal on cessation. The outcome of adaptation is often referred to as 'physical dependence' in pharmacology, as distinct from addiction, although these terms have unfortunately become conflated in some diagnostic guides. Physical dependence to antidepressants may occur in some patients, consistent with the fact that some patients experience withdrawal effects from these medications. It is thought that longer duration of use, higher dose and specific antidepressants affect the risk of antidepressant withdrawal effects as they might cause greater adaptation of the brain. We searched PubMed for relevant systematic reviews and other relevant analyses to summarise existing data on determinants of antidepressant withdrawal incidence, severity and duration. Overall, data were limited. From survey data, increased duration of use was associated with an increased incidence and severity of withdrawal effects, consistent with some evidence from data provided by drug manufacturers. Duration of use may be related to duration of withdrawal effects but data are heterogenous and sparse. Serotonin and noradrenaline reuptake inhibitors and paroxetine are associated with higher risks than other antidepressants, though data for some antidepressants are lacking. Higher doses of antidepressant has some weak association with an increased risk of withdrawal, with some ceiling effects, perhaps reflecting receptor occupancy relationships. Past experience of withdrawal effects is known to predict future risk. Based on these data, we outline a preliminary rubric for determining the risk of withdrawal symptoms for a particular patient, which may have relevance for determining tapering rates. Given the limited scope of the current research, future research should aim to clarify prediction of antidepressant withdrawal risk, especially by examining the risk of withdrawal in long-term users of medication, as well as the severity and duration of effects, to improve the preliminary tool for predictive purposes. Further research into the precise adaptations in long-term antidepressant use may improve the ability to predict withdrawal effects for a particular patient. [ABSTRACT FROM AUTHOR]

Developing and middle-income countries increasingly emphasize higher education and entrepreneurship in their long-term development strategy. Thus, our work focuses on the influence of higher education institutions (HEIs) on startup ecosystems in Brazil, an emerging economy. As traditional data to perform this type of study, such as surveys, are challenging to get, we propose an alternative approach. Given the growing capability of social media databases such as Crunchbase and LinkedIn to provide startup and individual-level data, we draw on computational methods to mine data for social network analysis. Our approach enables different types of analysis. First, we describe regional variability in entrepreneurial network characteristics. Second, we examine the influence of elite HEIs in economic hubs on entrepreneur networks. Third, we investigate the influence of the academic trajectories of startup founders, including their courses of study and HEIs of origin, on the fundraising capacity of startups. We find that HEI quality and the maturity of the ecosystem influence startup success. We also observe that elite HEIs have a powerful influence on local entrepreneur ecosystems. Surprisingly, while the most nationally prestigious HEIs in the South and Southeast have the longest geographical reach, their network influence remains local. This means that investments in entrepreneurship, in the Brazilian context, tend to remain concentrated in wealthier cities, and may actually reinforce or increase regional inequalities. We also find that the startup ecosystem in the wealthier South and Southeast is more diverse in terms of sectors, which is more advantageous to economic development. Our approach can be helpful, especially in countries with limited studies of the interaction between startups and institutional factors supporting them. In terms of policy recommendations, we would recommend more investment at the regional level in terms of cultivating entrepreneurship, given the limited spillover from wealthier regions. [ABSTRACT FROM AUTHOR]

Genome-wide association studies (GWASs) for osteoporotic traits have identified over 1000 associations; however, their impact has been limited by the difficulties of causal gene identification and a strict focus on bone mineral density (BMD). Here, we use Diversity Outbred (DO) mice to directly address these limitations by performing a systems genetics analysis of 55 complex skeletal phenotypes. We apply a network approach to cortical bone RNA-seq data to discover 66 genes likely to be causal for human BMD GWAS associations, including the genes SERTAD4 and GLT8D2. We also perform GWAS in the DO for a wide-range of bone traits and identify Qsox1 as a gene influencing cortical bone accrual and bone strength. In this work, we advance our understanding of the genetics of osteoporosis and highlight the ability of the mouse to inform human genetics. Osteoporosis GWAS faces two challenges, causal gene discovery and a lack of phenotypic diversity. Here, the authors use the Diversity Outbred mouse population to inform human GWAS using networks and map genetic loci for 55 bone traits, identifying new potential bone strength genes. [ABSTRACT FROM AUTHOR]

The field of sociology has long been subject to critique for alleged ideological bias and left-wing groupthink linked to its social justice mission. Critics contend that the construction of “sacred victims” by progressive intellectuals hinders their ability to objectively appraise the circumstances of such vulnerable groups. To address this criticism, we survey 479 sociologists in national universities and colleges in the U.S. regarding three sensitive controversies: urban poverty in the black community; gendered differences in occupational choices; and immigration. We find significant patterns in the data. Commitment to the field’s “moral mission,” preferred research paradigm, gender, and especially political orientation are all significant predictors of sociologists’ views. The results, we suggest, can be understood by conceptualizing the field of sociology as an “emotive community.” In doing so, we draw upon current social psychological research on moral foundations theory developed by Jonathan Haidt and colleagues. [ABSTRACT FROM AUTHOR]

Congenital prepubic sinus is a very rare urogenital anomaly that manifests as a tubular structure of varying histological findings that drains to the skin overlying the pubic symphysis. This tract has been observed to course above, below or, in only a handful of cases, directly through the pubis. We report a case of congenital prepubic sinus with this unusual transpubic course in an 18-year-old man. The patient was initially taken to the operating room for excision of a presumed inclusion cyst. At the time of surgery, the collection was found to track proximally and was excised down to the level of the pubic symphysis. Subsequent magnetic resonance (MR) imaging established the diagnosis of congenital prepubic sinus. We describe the different anatomical courses of congenital prepubic sinus, hypotheses of its pathogenesis, and the use of MR imaging in both diagnosis and surgical planning. [ABSTRACT FROM AUTHOR]

In recent years evolutionary theorists have been engaged in a protracted and bitter disagreement concerning how natural selection affects units such as genes, individuals, kin groups, and groups. Central to this debate has been whether selective pressures affecting group success can trump the selective pressures that confer advantage at the individual level. In short, there has been a debate about the utility of group selection, with noted theorist Steven Pinker calling the concept useless for the social sciences. We surveyed 175 evolutionary anthropologists to ascertain where they stood in the debate. We found that most were receptive to group selection, especially in the case of cultural group selection. The survey also revealed that liberals and conservatives, and males and females, all displayed significant differences of opinion concerning which selective forces were important in humanity's prehistory. We conclude by interpreting these findings in the context of recent research in political psychology. [ABSTRACT FROM AUTHOR]

Recent evidence has suggested that inflammatory and immune mechanisms may play a role in the pathophysiology of bipolar disorder (BD). Only a few studies have assessed the profile of chemokines, a family of chemotactic cytokines related to the recruitment of leukocytes, in BD. The objective of our study was to evaluate the plasma levels of chemokines in BD patients in different mood states in comparison with healthy controls. Seventy BD type I patients (35 in euthymia and 35 in mania), and 50 healthy controls matched by age, gender, and education level were enrolled in this study. All subjects were assessed by the Mini-International Neuropsychiatry Interview and the patients by the Young Mania Rating Scale and the Hamilton Depression Rating Scale. The plasma levels of CCL2, CCL3, CCL11, CCL24, CXCL8, and CXCL10 were measured by enzyme-linked immunosorbent assay. BD patients presented higher plasma levels of CCL11 (1.69-fold increase; p < 0.001), CCL24 (1.40-fold increase; p = 0.02), CXCL10 (1.45-fold increase; p < 0.001) and decreased plasma levels of CXCL8 (8.68-fold decrease p < 0.001). Logistic regression stressed the main effect of increased plasma levels of CXCL10 (OR = 1.009, 95 % CI = 1.000-1.018, p = 0.042) and CCL11 (OR = 1.002, 95 % CI = 1.001-1.003, p = 0.003) and decreased plasma levels of CXCL8 (OR = 0.995, 95 % CI = 0.990-0.999, p = 0.013) to BD. This study reinforces the view that BD is associated with an immune dysfunction. [ABSTRACT FROM AUTHOR]

In the mouse, each class of olfactory receptor neurons expressing a given odorant receptor has convergent axonal projections to two specific glomeruli in the olfactory bulb, thereby creating an odour map. However, it is unclear how this map is represented in the olfactory cortex. Here we combine rabies-virus-dependent retrograde mono-trans-synaptic labelling with genetics to control the location, number and type of 'starter' cortical neurons, from which we trace their presynaptic neurons. We find that individual cortical neurons receive input from multiple mitral cells representing broadly distributed glomeruli. Different cortical areas represent the olfactory bulb input differently. For example, the cortical amygdala preferentially receives dorsal olfactory bulb input, whereas the piriform cortex samples the whole olfactory bulb without obvious bias. These differences probably reflect different functions of these cortical areas in mediating innate odour preference or associative memory. The trans-synaptic labelling method described here should be widely applicable to mapping connections throughout the mouse nervous system. [ABSTRACT FROM AUTHOR]

Information about the 3rd International Conference on Osteoimmunology: Interactions of the Immune and Skeletal Systems held from June 21 to 25, 2010 in Santorini, Greece is presented. Topics include the interaction of osteoblast lineage cells with hematopoietic stem cells (HSCs), the regulation of bone lineage cell differentiation and the dealings of bone cells with inflammatory cells. The meeting featured key speakers including Takashi Nagasawa, Masaru Ishii and Georg Schett.

Microfluidic technology has developed greatly in recent years, enabling multiple analysis systems to be placed on a microfluidic chip. However, microfluidic large-scale integration of control elements analogous to those achieved in the microelectronics industry is still a challenge. We present an integrated microfluidic valve, compatible with standard soft-lithography processes, which has a pressure gain much greater than unity. We show that this enables integration of fully static digital control logic and state storage directly on-chip, ultimately enabling microfluidic-state machines to be designed. Outputs from this digital control logic can then be used to control traditional analyte flow valves. This strategy enables much of the bulky external hardware at present used to control pneumatically driven microfluidic chips in the laboratory to be transferred onto the microfluidic chip, which drastically reduces the required number of external chip connections. [ABSTRACT FROM AUTHOR]

Information about several papers discussed at a conference titled "International Conference on Osteoimmunology: Interactions of the Immune and Skeletal Systems" is presented. Topics include the interaction of osteoblast lineage cells with hematopoietic stem cells (HSCs) and the interactions of bone cells with inflammatory cells. The conference featured several speakers including Henry Kronenberg, Theresa Guise, and Debra Zack.

The diagnosis and management of adolescent urinary tract infection (UTI) share some of the clinical features seen in infections of the young and old. Whereas most infections in the young patient demand an extensive radiologic work-up, the teenager with a UTI is not so straightforward. The clinician must balance being too aggressive with being too conservative in the diagnosis and management of these patients. UTIs occur most frequently among adolescent females and are usually uncomplicated and not associated with underlying anatomic abnormalities. Smaller numbers of adolescent males suffer from UTIs, and the need to search for underlying abnormalities is not clear. Adolescent UTI is associated with nascent sexual activity and is also more common in voiding/elimination syndromes. Future studies examining UTI, specifically in the adolescent age group, will help provide clinicians with a more focused algorithm in the diagnosis and management of adolescent UTIs. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor-I (IGF-I) is critical for optimal skeletal growth and maintenance. Knockout and transgenic models have provided significant insights into the role of IGF-I in bone modeling and remodeling. Congenic mice demonstrate allelic differences in particular quantitative trait loci (QTL). One such model is congenic 6T, which contains a QTL for reduced serum IGF-I donated from C3H/HeJ on a pure C57Bl/6 J (B6) background. In this study we found a 30%-50% reduction in IGF-I expression in bone, liver, and fat of the congenic 6T mouse, as well as lower circulating IGF-I compared with control B6. 6T mice also had a greater percentage body fat, but reduced serum leptin. These changes were associated with reduced cortical and trabecular bone mineral density, impaired bone formation but no change in bone resorption. Moreover, the anabolic skeletal response to intermittent parathyroid hormone (PTH) therapy was blunted in 6T compared with B6, potentially in response to greater programmed cell death in osteocytes and osteoblasts of 6T. In summary, allelic differences in IGF-I expression impact peak bone acquisition and body composition, as well as the skeletal response to PTH. Lifelong changes in circulating and skeletal IGF-I may be relevant for the pathophysiology of several diseases, including chronic renal failure. [ABSTRACT FROM AUTHOR]

Neurofibroma cell lines derived from mice transgenic for HTLV-I LTR tax express high levels of HTLV-I tax mRNA and protein and exhibit a transformed phenotype. A retrovirus vector carrying HTLV-I tax cDNA in reversed transcriptional orientation was stably transfected into the neurofibroma cells. Antisense RNA inhibited expression of the tax gene with a decrease of more than 40% in both tax mRNA and protein. Tax antisense RNA reversed the transformed phenotype as exhibited by dramatic changes in cell morphology and growth characteristics. Expression of several cellular genes which are activated by Tax protein including GM-CSF, IL-6, LT/TNF, c-myc and LIF was down-regulated, while M-CSF and c-src proto-oncogene expressions were up-regulated. Accumulation of β-actin mRNA was not affected. The changes that occurred in the tax antisense expressing neurofibroma cells could be the consequence of the decreased concentration of Tax protein. These results also indicate that HTLV-I Tax protein is crucial for maintaining the transformed cell morphology, growth and proliferation of murine neurofibroma cells and suggest that deregulation of endogenous cellular genes by Tax protein is the mechanism through which neurofibromas occur in tax mice. [ABSTRACT FROM AUTHOR]

The pediatric radiologist plays a significant role in the evaluation and the treatment of infants with ambiguous genitalia. On the first day of life, an investigation should be initiated that includes studies, in particular a sonogram, to demonstrate the presence or absence of a uterus, and a genitogram to define the presence of a vagina. Once gender assignment has been made, information regarding the size of the vagina and its position in regard to the urogenital sinus becomes essential to the pediatric urologist when planning a course for reconstruction. Herein we break down intersex states into four major categories: female pseudohermaphroditism, male pseudohermaphroditism without müllerian structures, and male hermaphroditism with müllerian structures and true hermaphroditism. The role of the radiologist in each of these states is discussed. [ABSTRACT FROM AUTHOR]

We have produced a monoclonal antibody, Y-7, that reacts with a Qa-2 region-controlled determinant. Cellular and strain distribution analyses, coupled with quantitative variation in the amount of Y-7 antigen expressed among strains, provide overwhelming evidence that Y-7 reacts with the Qa-2 determinant. The determinant detected by Y-7 is differentially expressed in T and B lymphocytes in a strain specific manner. Y-7 reacts with the majority of T lymphocytes (> 95%) and approximately one-half of B lymphocytes in certain strains (++ strains), and with the majority of T lymphocytes (> 95%) and no B lymphocytes in other strains (+ strains). T lymphocytes in + strains express approximately three fold less of the Y-7 determinant than T lymphocytes from ++ strains. In addition, we show that the Y-7 determinant is expressed in approximately one-third to one-half of Lyb-3, 5 B lymphocytes. Possible mechanisms determining quantitative and qualitative variation in the expression of the Y-7 determinant in T and B lymphocytes are discussed. [ABSTRACT FROM AUTHOR]

This article proposes a completion-detection method for efficiently implementing Boolean functions as self-timed logic structures. Current-Sensing Completion Detection, CSCD, allows self-timed circuits to be designed using single-rail variable encoding (one signal wire per logic variable) and implemented in about the same silicon area as an equivalent synchronous implementation. Compared to dual-rail encoding methods, CSCD can reduce the number of signal wires and transistors used by approximately 50%. CSCD implementations improved performance over equivalent dual-rail designs because of: (1) reduced parasitic capacitance, (2) removal of spacer tokens in the data stream, and (3) computation state similarity of consecutive data variables. Several CSCD configurations are described and evaluated and transistor-level implementations are provided for comparison. [ABSTRACT FROM AUTHOR]

Abnormal axonal transport is associated with neuronal disease. We identified a role for DHC-1, the C. elegans dynein heavy chain, in maintaining neuronal cargo distribution. Surprisingly, this does not involve dynein's role as a retrograde motor in cargo transport, hinging instead on its ability to inhibit microtubule (MT) dynamics. Neuronal MTs are highly static, yet the mechanisms and functional significance of this property are not well understood. In disease-mimicking dhc-1 alleles, excessive MT growth and collapse occur at the dendrite tip, resulting in the formation of aberrant MT loops. These unstable MTs act as cargo traps, leading to ectopic accumulations of cargo and reduced availability of cargo at normal locations. Our data suggest that an anchored dynein pool interacts with plus-end-out MTs to stabilize MTs and allow efficient retrograde transport. These results identify functional significance for neuronal MT stability and suggest a mechanism for cellular dysfunction in dynein-linked disease. [ABSTRACT FROM AUTHOR]

Investigates kidney cysts in children. Sonographic criteria for diagnosing cysts; Diagnosis of simple cysts through computerized tomography; Clinical manifestations of cysts including cystic mass, hydronephrosis, abscess, solid tumor or bleeding, hematoma and a calyceal diverticulum; Estimated percentage of incidence of simple renal cysts among children; Syndromes associated with the cysts.

The article presents abstracts on osteoimmunology topics which include the role of interleukin 6 (IL-6) in the development of breast and prostate cancer metastases to bone, actions of insulin on the skeleton, and how integrin signaling regulated the osteoclast cytoskeleton.