Toward a Census of Bacteria in Soil

For more than a century, microbiologists have sought to determine the species richness of bacteria in soil, but the extreme complexity and unknown structure of soil microbial communities have obscured the answer. We developed a statistical model that makes the problem of estimating richness statistically accessible by evaluating the characteristics of samples drawn from simulated communities with parametric community distributions. We identified simulated communities with rank-abundance distributions that followed a truncated lognormal distribution whose samples resembled the structure of 16S rRNA gene sequence collections made using Alaskan and Minnesotan soils. The simulated communities constructed based on the distribution of 16S rRNA gene sequences sampled from the Alaskan and Minnesotan soils had a richness of 5,000 and 2,000 operational taxonomic units (OTUs), respectively, where an OTU represents a collection of sequences not more than 3% distant from each other. To sample each of these OTUs in the Alaskan 16S rRNA gene library at least twice, 480,000 sequences would be required; however, to estimate the richness of the simulated communities using nonparametric richness estimators would require only 18,000 sequences. Quantifying the richness of complex environments such as soil is an important step in building an ecological framework. We have shown that generating sufficient sequence data to do so requires less sequencing effort than completely sequencing a bacterial genome

Altered expression of Alzheimer\u27s disease-related proteins in male hypogonadal mice

Age-related depletion of estrogens and androgens is associated with an increase in Alzheimer\u27s disease (AD) brain pathology and diminished cognitive function. Here we investigated AD-associated molecular and cellular changes in brains of aged hypogonadal (hpg) male and female mice. hpg Mice have a spontaneous, inactivating genetic mutation in the GnRH gene resulting in lifelong deficiency of gonadotropins and gonadal sex hormones. Western blot analysis revealed low levels of amyloid precursor protein and high levels of presenilin 1, amyloid precursor protein C-terminal fragment, and β-amyloid 42 in brains of aged male, but not female, hpg mice. Changes were confined to the hippocampus and were not evident in the cerebellum or other brain tissues. Male hpg mice tended to have lower levels of IL-1β protein than male littermate controls. Immunohistochemical staining of the basal forebrain revealed that male hpg mice had lower choline acetyltransferase levels per neuron compared with controls. These AD-like changes specific to male hpg mice supports a link between androgen depletion and the development of AD pathology

Does combined osteopenia/osteoporosis and sarcopenia confer greater risk of falls and fracture than either condition alone in older men? The Concord Health and Ageing in Men Project

Background It is unclear whether older men with osteopenia/osteoporosis and sarcopenia (so-called osteosarcopenia) are at greater risk of falls and fractures than those with either condition alone. Methods One thousand five hundred seventy-five community-dwelling men aged ≥70 years had appendicular lean mass, total hip and lumbar spine bone mineral density determined by dual-energy x-ray absorptiometry, and completed hand grip strength and gait speed tests. Osteopenia/osteoporosis was defined as a T-score at any site ≤−1.0 SD. Sarcopenia was defined using the European Working Group on Sarcopenia algorithm. Participants were contacted every 4 months for 6 ± 2 years to ascertain incident fractures (confirmed by radiographic reports) and for 2 years for incident falls. Results Prevalence of osteosarcopenia was 8%, while 34% of participants had osteopenia/osteoporosis alone and 7% had sarcopenia alone. Men with osteosarcopenia had significantly increased fall (incidence rate ratio: 1.41; 95% confidence interval [CI]: 1.02 to 1.95) and fracture risk (hazard ratio: 1.87; 95% CI: 1.07 to 3.26) compared with men with neither osteopenia/osteoporosis nor sarcopenia. There was no statistical interaction between osteopenia/osteoporosis and sarcopenia, and falls and fracture risk were not different for osteosarcopenia compared with either condition alone (all p > .05). Conclusions Community-dwelling older men with combined osteopenia/osteoporosis and sarcopenia do not have increased falls and fracture risk compared with those with either condition. Further research is required to clarify whether the term “osteosarcopenia” has any meaning above and beyond either term alone and therefore potential clinical utility for falls and fracture prediction.NHMRC (project grant number 301916) and the Ageing and Alzheimer’s Institute. D.Scott is supported by a NHRMC Career Development Fellowship (GNT1123014

Evaluating Calculated Free Testosterone as a Predictor of Morbidity and Mortality Independent of Testosterone for Cross-sectional and 5-Year Longitudinal Health Outcomes in Older Men: The Concord Health and Ageing in Men Project

To determine whether calculated free testosterone (cFT) provides prognostic information independent of serum T for predicting morbidity and mortality in older men in cross-sectional and 5-year longitudinal analyses. We studied men aged ≥70 years at baseline (n = 1,705), 2-year and 5-year measuring serum T (liquid chromatography-mass spectrometry), SHBG (immunoassay), cFT (an assumption-free empirical formula) together with 24 morbidity and 4 mortality outcomes. For cross-sectional and longitudinal analyses we employed a joint prediction model using generalized estimating equation models adjusted for age, smoking, comorbidities, and body mass index (BMI) with men having both normal T and normal cFT as referent group. Most morbidity and mortality outcomes were predicted by a combination of low T and cFT (LL). By contrast, only a single morbidity outcome in cross-sectional and none in longitudinal analysis was predicted by low T/normal cFT (LN) or normal T/low cFT (NL) without significant LL associations (isolated discordance). While for the few outcomes that predicted morbidity in men with discordances (LN or NL), these predictions only occurred when LL was also significant. Hence, for morbidity or mortality prediction in older men, discordance between cFT and T is unusual and isolated discordance is rare, so that cFT provides minimal independent prognostic information over serum T.NHMRC, Sydney Medical School Foundation, and Ageing and Alzheimer’s Institute

Community-dwelling men with dementia are at high risk of hip but not any other fracture: The Concord Health and Ageing in Men Project

Aim The aim of the present longitudinal study of community‐dwelling older men was to examine the association between cognitive status at baseline, and falls, fractures and bone loss over time. Methods In the Concord Health and Aging in Men Project, 1705 community‐dwelling men aged 70–97 years had detailed baseline clinical assessment of cognitive status (dementia, mild cognitive impairment [MCI] and normal cognition), as well as depression, physical activity, neuromuscular function, health status, sociodemographics, comorbidities, medication use and serum 25 hydroxyvitamin D, 1,25 dihydroxyvitamin D and parathyroid hormone levels. During a mean follow‐up period of 6 years, participants were contacted 4‐monthly to ascertain incident falls and fractures, the latter being confirmed by radiographic reports. Bone mineral density was measured by dual X‐ray absorptiometry at multiple time‐points. Results At baseline, 120 men were assessed to have MCI and 93 men to have dementia. Over time, there were 162 first incident fractures, including 43 hip and 32 vertebral fractures. In univariate models, baseline dementia, but not MCI, predicted an increased incidence of hip fracture (HR 6.95, 95% CI 3.47–13.96), but not vertebral (HR 2.26, 95% CI 0.79–6.46) or non‐hip non‐vertebral fracture (HR 0.73, 95% CI 0.27–1.99). The strong risk of hip fractures associated with dementia remained after accounting for potential confounders (HR 4.44, 95% CI 1.97–9.98). In multivariate analyses, dementia (incidence rate ratio 2.26, 95% CI 1.70–2.99), but not MCI, was associated with an increased risk of falls compared with normal cognition. There was no association between baseline dementia and change in bone mineral density. Conclusions Older men with dementia, but not MCI, have a greater tendency to fall and sustain hip fractures, but not any other types of fractures.NHMRC, Ageing and Alzheimer's Institute, Sydney Medical School Foundatio

Contributions of gut bacteria to Bacillus thuringiensis-induced mortality vary across a range of Lepidoptera

Abstract Background Gut microbiota contribute to the health of their hosts, and alterations in the composition of this microbiota can lead to disease. Previously, we demonstrated that indigenous gut bacteria were required for the insecticidal toxin of Bacillus thuringiensis to kill the gypsy moth, Lymantria dispar. B. thuringiensis and its associated insecticidal toxins are commonly used for the control of lepidopteran pests. A variety of factors associated with the insect host, B. thuringiensis strain, and environment affect the wide range of susceptibilities among Lepidoptera, but the interaction of gut bacteria with these factors is not understood. To assess the contribution of gut bacteria to B. thuringiensis susceptibility across a range of Lepidoptera we examined larval mortality of six species in the presence and absence of their indigenous gut bacteria. We then assessed the effect of feeding an enteric bacterium isolated from L. dispar on larval mortality following ingestion of B. thuringiensis toxin. Results Oral administration of antibiotics reduced larval mortality due to B. thuringiensis in five of six species tested. These included Vanessa cardui (L.), Manduca sexta (L.), Pieris rapae (L.) and Heliothis virescens (F.) treated with a formulation composed of B. thuringiensis cells and toxins (DiPel), and Lymantria dispar (L.) treated with a cell-free formulation of B. thuringiensis toxin (MVPII). Antibiotics eliminated populations of gut bacteria below detectable levels in each of the insects, with the exception of H. virescens, which did not have detectable gut bacteria prior to treatment. Oral administration of the Gram-negative Enterobacter sp. NAB3, an indigenous gut resident of L. dispar, restored larval mortality in all four of the species in which antibiotics both reduced susceptibility to B. thuringiensis and eliminated gut bacteria, but not in H. virescens. In contrast, ingestion of B. thuringiensis toxin (MVPII) following antibiotic treatment significantly increased mortality of Pectinophora gossypiella (Saunders), which was also the only species with detectable gut bacteria that lacked a Gram-negative component. Further, mortality of P. gossypiella larvae reared on diet amended with B. thuringiensis toxin and Enterobacter sp. NAB3 was generally faster than with B. thuringiensis toxin alone. Conclusion This study demonstrates that in some larval species, indigenous gut bacteria contribute to B. thuringiensis susceptibility. Moreover, the contribution of enteric bacteria to host mortality suggests that perturbations caused by toxin feeding induce otherwise benign gut bacteria to exert pathogenic effects. The interaction between B. thuringiensis and the gut microbiota of Lepidoptera may provide a useful model with which to identify the factors involved in such transitions.http://deepblue.lib.umich.edu/bitstream/2027.42/112871/1/12915_2008_Article_219.pd

Blood testosterone threshold for androgen deficiency symptoms.

There are few systematic studies of the relationship between blood testosterone concentrations and the symptoms of overt androgen deficiency. Because most testosterone preparations are relatively short-term, the rapid changes in blood testosterone concentrations they cause make it difficult to define any testosterone threshold. By contrast, subdermal testosterone implants provide stable blood testosterone concentrations over days to weeks, while gradually declining to baseline over 5-7 months. Hence, this provides an opportunity to define a blood testosterone threshold for androgen deficiency symptoms by observing androgen-deficient men as their familiar androgen deficiency symptoms return as testosterone pellets slowly dissolve. Among 52 androgen-deficient men who underwent 260 implantations over 5 yr, at the time of return of androgen deficiency symptoms the blood total and free testosterone concentrations were highly reproducible within individuals (F ‫؍‬ 0.8, P ‫؍‬ 0.49 and F ‫؍‬ 1.4, 0.24, respectively) but varied markedly between men (F ‫؍‬ 167 and F ‫؍‬ 138, both P < 0.001), indicating that each person had a consistent testosterone threshold for androgen deficiency symptoms that differed markedly between individuals. The most reported symptoms of androgen deficiency were lack of energy, lack of motivation, and reduced libido. The symptomatic threshold was significantly lower in men with secondary hypogonadism compared with men with primary or mixed hypogonadism (total, 9.7 ؎ 0.5 nmol/liter vs. T HE EFFECTS OF androgen deficiency and replacement on objective endpoints, notably bone (1, 2) and muscle (3-7), are well known and increasingly studied. Yet, whereas symptoms of androgen deficiency are discussed in textbooks and form the basis for practical clinical monitoring of androgen replacement therapy (8), there is a paucity of systematic studies of the symptoms of, and symptomatic threshold for, androgen deficiency. The subjective effects of androgen deficiency and replacement have generally been studied as objectively recorded measures of mood, behavior and cognitive responses (9 -11), but symptoms themselves are more difficult to study objectively. As a result, subjective effects of androgens have received most attention in the psychology literature, where empirical studies are, however, largely observational and restricted to eugonadal men limiting the salience of any inferences regarding relationships of blood testosterone concentrations to symptoms of overt androgen deficiency. A major limitation of interventional clinical research on androgen deficiency symptoms is that the available relatively short-term testosterone preparations produce swings in blood testosterone levels over days to weeks, which make it difficult or impossible to distinguish reliably symptom resolution and reappearance from pharmacological effects. The present study overcomes this limitation by using a long-acting depot testosterone preparation, which maintains stable blood testosterone concentrations over days to weeks but, as the biodegradable implants erode, allows them to decline slowly back to baseline over 5-7 months (12-15). Because the treated men return for blood testosterone measurement and reimplantation when their familiar androgen deficiency symptoms return, this allows a prospective evaluation of the relationships between individual androgen deficiency symptoms and the blood testosterone concentrations that accompany them. Subjects and Methods Patients We reviewed prospectively collected data from patients having regular androgen replacement therapy with a standard dose (four 200-mg pellets) of subdermal testosterone implants for androgen deficiency as described previously Procedures Implantation procedure. Testosterone pellet implantation procedures are booked throughout the week. At visits, men have a blood sample drawn JCEM is published monthly by The Endocrine Society (http://www. endo-society.org), the foremost professional society serving the endocrine community

Adolescent testosterone influences BDNF and TrkB mRNA and neurotrophin–interneuron marker relationships in mammalian frontal cortex

AbstractLate adolescence in males is a period of increased susceptibility for the onset of schizophrenia, coinciding with increased circulating testosterone. The cognitive deficits prevalent in schizophrenia may be related to unhealthy cortical interneurons, which are trophically dependent on brain derived neurotrophic factor. We investigated, under conditions of depleted (monkey and rat) and replaced (rat) testosterone over adolescence, changes in gene expression of cortical BDNF and TrkB transcripts and interneuron markers and the relationships between these mRNAs and circulating testosterone. Testosterone removal by gonadectomy reduced gene expression of some BDNF transcripts in monkey and rat frontal cortices and the BDNF mRNA reduction was prevented by testosterone replacement. In rat, testosterone replacement increased the potential for classical TrkB signalling by increasing the full length to truncated TrkB mRNA ratio, whereas in the monkey cortex, circulating testosterone was negatively correlated with the TrkB full length/truncated mRNA ratio. We did not identify changes in interneuron gene expression in monkey frontal cortex in response to gonadectomy, and in rat, we showed that only somatostatin mRNA was decreased by gonadectomy but not restored by testosterone replacement. We identified complex and possibly species-specific, relationships between BDNF/TrkB gene expression and interneuron marker gene expression that appear to be dependent on the presence of testosterone at adolescence in rat and monkey frontal cortices. Taken together, our findings suggest there are dynamic relationships between BDNF/TrkB and interneuron markers that are dependent on the presence of testosterone but that this may not be a straightforward increase in testosterone leading to changes in BDNF/TrkB that contributes to interneuron health