Multimeric bivalent immunogens from recombinant tetanus toxin H<Subscript>C</Subscript> fragment,synthetic hexasaccharides,and a glycopeptide adjuvant

Using recombinant tetanus toxin H_C fragment (rTT-H_C) as carrier, we prepared multimeric bivalent immunogens featuring the synthetic hexasaccharide fragment of O-PS of Vibrio cholerae O:1, serotype Ogawa, in combination with either the synthetic hexasaccharide fragment of O-PS of Vibrio cholerae O:1, serotype Inaba, or a synthetic disaccharide tetrapeptide peptidoglycan fragment as adjuvant. The conjugation reaction was effected by squaric acid chemistry and monitored in virtually real time by SELDI-TOF MS. In this way, we could prepare well-defined immunogens with predictable carbohydrate–carrier ratio, whose molecular mass and the amount of each saccharide attached could be independently determined. The ability to prepare such neoglycoconjugates opens unprecedented possibilities for preparation of conjugate vaccines for bacterial diseases from synthetic carbohydrates.     

Combinatorial lentiviral gene delivery of pro-oligodendrogenic factors for improving myelination of regenerating axons after spinal cord injury

Spinal cord injury (SCI) results in paralysis below the injury and strategies are being developed that support axonal regrowth, yet recovery lags, in part, because many axons are not remyelinated. Herein, we investigated strategies to increase myelination of regenerating axons by overexpression of platelet-derived growth factor (PDGF)-AA and noggin either alone or in combination in a mouse SCI model. Noggin and PDGF-AA have been identified as factors that enhance recruitment and differentiation of endogenous progenitors to promote myelination. Lentivirus encoding for these factors was delivered from a multichannel bridge, which we have previously shown creates a permissive environment and supports robust axonal growth through channels. The combination of noggin+PDGF enhanced total myelination of regenerating axons relative to either factor alone, and importantly, enhanced functional recovery relative to the control condition. The increase in myelination was consistent with an increase in oligodendrocyte-derived myelin, which was also associated with a greater density of cells of an oligodendroglial lineage relative to each factor individually and control conditions. These results suggest enhanced myelination of regenerating axons by noggin+PDGF that act on oligodendrocyte-lineage cells post-SCI, which ultimately led to improved functional outcomes.     

Larval dispersal and movement patterns of coral reef fishes,and implications for marine reserve network design

Well‐designed and effectively managed networks of marine reserves can be effective tools for both fisheries management and biodiversity conservation. Connectivity, the demographic linking of local populations through the dispersal of individuals as larvae, juveniles or adults, is a key ecological factor to consider in marine reserve design, since it has important implications for the persistence of metapopulations and their recovery from disturbance. For marine reserves to protect biodiversity and enhance populations of species in fished areas, they must be able to sustain focal species (particularly fishery species) within their boundaries, and be spaced such that they can function as mutually replenishing networks whilst providing recruitment subsidies to fished areas. Thus the configuration (size, spacing and location) of individual reserves within a network should be informed by larval dispersal and movement patterns of the species for which protection is required. In the past, empirical data regarding larval dispersal and movement patterns of adults and juveniles of many tropical marine species have been unavailable or inaccessible to practitioners responsible for marine reserve design. Recent empirical studies using new technologies have also provided fresh insights into movement patterns of many species and redefined our understanding of connectivity among populations through larval dispersal. Our review of movement patterns of 34 families (210 species) of coral reef fishes demonstrates that movement patterns (home ranges, ontogenetic shifts and spawning migrations) vary among and within species, and are influenced by a range of factors (e.g. size, sex, behaviour, density, habitat characteristics, season, tide and time of day). Some species move <0.1–0.5 km (e.g. damselfishes, butterflyfishes and angelfishes), <0.5–3 km (e.g. most parrotfishes, goatfishes and surgeonfishes) or 3–10 km (e.g. large parrotfishes and wrasses), while others move tens to hundreds (e.g. some groupers, emperors, snappers and jacks) or thousands of kilometres (e.g. some sharks and tuna). Larval dispersal distances tend to be <5–15 km, and self‐recruitment is common. Synthesising this information allows us, for the first time, to provide species, specific advice on the size, spacing and location of marine reserves in tropical marine ecosystems to maximise benefits for conservation and fisheries management for a range of taxa. We recommend that: (i) marine reserves should be more than twice the size of the home range of focal species (in all directions), thus marine reserves of various sizes will be required depending on which species require protection, how far they move, and if other effective protection is in place outside reserves; (ii) reserve spacing should be <15 km, with smaller reserves spaced more closely; and (iii) marine reserves should include habitats that are critical to the life history of focal species (e.g. home ranges, nursery grounds, migration corridors and spawning aggregations), and be located to accommodate movement patterns among these. We also provide practical advice for practitioners on how to use this information to design, evaluate and monitor the effectiveness of marine reserve networks within broader ecological, socioeconomic and management contexts.     

Cell Signaling-Based Classifier Predicts Response to Induction Therapy in Elderly Patients with Acute Myeloid Leukemia

Single-cell network profiling (SCNP) data generated from multi-parametric flow cytometry analysis of bone marrow (BM) and peripheral blood (PB) samples collected from patients >55 years old with non-M3 AML were used to train and validate a diagnostic classifier (DX_SCNP) for predicting response to standard induction chemotherapy (complete response [CR] or CR with incomplete hematologic recovery [CRi] versus resistant disease [RD]). SCNP-evaluable patients from four SWOG AML trials were randomized between Training (N = 74 patients with CR, CRi or RD; BM set = 43; PB set = 57) and Validation Analysis Sets (N = 71; BM set = 42, PB set = 53). Cell survival, differentiation, and apoptosis pathway signaling were used as potential inputs for DX_SCNP. Five DX_SCNP classifiers were developed on the SWOG Training set and tested for prediction accuracy in an independent BM verification sample set (N = 24) from ECOG AML trials to select the final classifier, which was a significant predictor of CR/CRi (area under the receiver operating characteristic curve AUROC = 0.76, p = 0.01). The selected classifier was then validated in the SWOG BM Validation Set (AUROC = 0.72, p = 0.02). Importantly, a classifier developed using only clinical and molecular inputs from the same sample set (DX_CLINICAL2) lacked prediction accuracy: AUROC = 0.61 (p = 0.18) in the BM Verification Set and 0.53 (p = 0.38) in the BM Validation Set. Notably, the DX_SCNP classifier was still significant in predicting response in the BM Validation Analysis Set after controlling for DX_CLINICAL2 (p = 0.03), showing that DX_SCNP provides information that is independent from that provided by currently used prognostic markers. Taken together, these data show that the proteomic classifier may provide prognostic information relevant to treatment planning beyond genetic mutations and traditional prognostic factors in elderly AML.     

Cardiovascular Disease Risk of Abdominal Obesity vs. Metabolic Abnormalities

It remains unclear whether abdominal obesity increases cardiovascular disease (CVD) risk independent of the metabolic abnormalities that often accompany it. Therefore, the objective of this study was to evaluate the independent effects of abdominal obesity vs. metabolic syndrome and diabetes on the risk for incident coronary heart disease (CHD) and stroke. The Framingham Offspring, Atherosclerosis Risk in Communities, and Cardiovascular Health studies were pooled to assess the independent effects of abdominal obesity (waist circumference >102 cm for men and >88 cm for women) vs. metabolic syndrome (excluding the waist circumference criterion) and diabetes on risk for incident CHD and stroke in 20,298 men and women aged ≥45 years. The average follow‐up was 8.3 (s.d. 1.9) years. There were 1,766 CVD events. After adjustment for demographic factors, smoking, alcohol intake, number of metabolic syndrome components, and diabetes, abdominal obesity was not significantly associated with an increased risk of CVD (hazard ratio (HR) (95% confidence interval): 1.09 (0.98, 1.20)). However, after adjustment for demographics, smoking, alcohol intake, and abdominal obesity, having 1–2 metabolic syndrome components, the metabolic syndrome and diabetes were each associated with a significantly increased risk of CVD (2.12 (1.80, 2.50), 2.82 (1.92, 4.12), and 5.33 (3.37, 8.41), respectively). Although abdominal obesity is an important clinical tool for identification of individuals likely to possess metabolic abnormalities, these data suggest that the metabolic syndrome and diabetes are considerably more important prognostic indicators of CVD risk.     

Ecological and acoustic responses of bush crickets to anthropogenic and natural ecotones

Biodiversity and Conservation - Ecotones occur naturally throughout complex landscapes. Each ecotone has particular ecological conditions resulting in species-specific responses. Across...