Several studies have shown that long-term survival after acute kidney injury (AKI) is reduced even if there is clinical recovery. However, we recently reported that in septic shock patients those that recover from AKI have survival similar to patients without AKI. Here, we studied a cohort with less severe sepsis to examine the effects of AKI on longer-term survival as a function of recovery by discharge.

Although bioinformatics is becoming increasingly central to research in the life sciences, bioinformatics skills and knowledge are not well integrated into undergraduate biology education. This curricular gap prevents biology students from harnessing the full potential of their education, limiting their career opportunities and slowing research innovation. To advance the integration of bioinformatics into life sciences education, a framework of core bioinformatics competencies is needed. To that end, we here report the results of a survey of biology faculty in the United States about teaching bioinformatics to undergraduate life scientists. Responses were received from 1,260 faculty representing institutions in all fifty states with a combined capacity to educate hundreds of thousands of students every year. Results indicate strong, widespread agreement that bioinformatics knowledge and skills are critical for undergraduate life scientists as well as considerable agreement about which skills are necessary. Perceptions of the importance of some skills varied with the respondent's degree of training, time since degree earned, and/or the Carnegie Classification of the respondent's institution. To assess which skills are currently being taught, we analyzed syllabi of courses with bioinformatics content submitted by survey respondents. Finally, we used the survey results, the analysis of the syllabi, and our collective research and teaching expertise to develop a set of bioinformatics core competencies for undergraduate biology students. These core competencies are intended to serve as a guide for institutions as they work to integrate bioinformatics into their life sciences curricula.

Bladder cancer (BC) is one of the most common urologic malignancies and it is urgently needed to identify novel potential prognostic biomarkers for predicting prognosis and progression of patients with BC in clinical practice. Previous research has revealed that long noncoding RNAs (lncRNAs) played critical roles in BC, and may serve as novel potential prognostic biomarkers in patients with BC. Therefore, we conducted this meta-analysis to clarify the prognostic potential of lncRNAs in BC patients.

Multi-stakeholder platforms (MSPs) have been playing an increasing role in interventions aiming to generate and scale innovations in agricultural systems. However, the contribution of MSPs in achieving innovations and scaling has been varied, and many factors have been reported to be important for their performance. This paper aims to provide evidence on the contribution of MSPs to innovation and scaling by focusing on three developing country cases in Burundi, Democratic Republic of Congo, and Rwanda. Through social network analysis and logistic models, the paper studies the changes in the characteristics of multi-stakeholder innovation networks targeted by MSPs and identifies factors that play significant roles in triggering these changes. The results demonstrate that MSPs do not necessarily expand and decentralize innovation networks but can lead to contraction and centralization in the initial years of implementation. They show that some of the intended next users of interventions with MSPs-local-level actors-left the innovation networks, whereas the lead organization controlling resource allocation in the MSPs substantially increased its centrality. They also indicate that not all the factors of change in innovation networks are country specific. Initial conditions of innovation networks and funding provided by the MSPs are common factors explaining changes in innovation networks across countries and across different network functions. The study argues that investigating multi-stakeholder innovation network characteristics targeted by the MSP using a network approach in early implementation can contribute to better performance in generating and scaling innovations, and that funding can be an effective implementation tool in developing country contexts.

The fat mass- and obesity-associated gene (FTO) is significantly associated with obesity, but the associations of FTO with obesity-related traits are not fully described. We aimed to investigate the association of the FTO single nucleotide polymorphism (SNP) rs6499640 with lipid levels in Chinese children. A total of 3503 children aged 6-18 years were included in the present study. Lipid levels were analyzed and the SNP rs6499640 was genotyped using the TaqMan Allelic Discrimination Assay. Statistically significant associations were found between rs6499640 and low-density lipoprotein cholesterol (LDL-C) (p = 0.008), total cholesterol (TC) (p = 0.005), and triglycerides (TG) (p < 0.001) in girls under a dominant model adjusted for age and BMI. No statistical significance was found between the SNP and lipid levels in boys. We demonstrated for the first time that the SNP rs6499640 in FTO is associated with LDL-C, TC, and TG in Chinese girls. Our study identified a new risk locus for lipid levels in children.

The regenerative process after tissue damage relies on a variety of cellular responses that includes compensatory cell proliferation and cell fate re-specification. The identification of the signalling networks regulating these cellular events is a central question in regenerative biology. Tissue regeneration models in Drosophila have shown that two of the signals that play a fundamental role during the early stages of regeneration are the c-Jun N-terminal kinase (JNK) and JAK/STAT signalling pathways. These pathways have been shown to be required for controlling regenerative proliferation, however their contribution to the processes of cellular reprogramming and cell fate re-specification that take place during regeneration are largely unknown. Here, we present evidence for a previously unrecognised function of the cooperative activities of JNK and JAK/STAT signalling pathways in inducing loss of cell fate specification in imaginal discs. We show that co-activation of these signalling pathways induces both the cell fate changes in injured areas, as well as in adjacent cells. We have also found that this function relies on the activity of the Caspase initiator encoded by the gene dronc.

Efforts to develop preventatives against HIV infection through sexual route have identified, among many, algal lectins as the potent molecules for scaffolding HIV entry inhibition. Algal lectin scytovirin (SVN) from Scytonema varium, a cyanobacterium, has anti-HIV effects with the potential for use in sculpting HIV neutralization. We created a recombinant strain of human vaginal L. plantarum for extracellular expression of recombinant (r)SVN. The rSVN protein containing culture supernatant was analyzed for its binding with HIV-1 gp160, and for inhibiting infection with primary R5 and X4 HIV-1 strains in TZM-bl cells. The rSVN protein extant in recombinant L. plantarum culture supernatant binds to HIV-1 gp160 and reduces the HIV-induced cytopathic effect to nearly 56.67% and 86.47% in R5 and X4 HIV-1 infected TZM-bl cells, respectively. The fortified L. plantarum may be explored for its use as a live virucide in vaginal mucosa of high risk women to prevent HIV entry.

CCAAT/enhancer binding protein β (C/EBPβ) is required for murine mammary ductal morphogenesis and alveologenesis. Progesterone is critical for proliferation and alveologenesis in adult mammary glands, and there is a similar requirement for progesterone receptor isoform B (PRB) in alveologenesis. We examined C/EBPβ regulation of PR expression. All three C/EBPβ isoforms, including typically inhibitory LIP, transactivated the PR promoter. LIP, particularly, strongly synergized with c-Jun to drive PR transcription. Endogenous C/EBPβ and c-Jun stimulated a PR promoter-reporter and these two factors showed promoter occupancy on the endogenous PR gene. Additionally, LIP overexpression elevated endogenous PR protein expression. In pregnancy, both PRB and the relative abundance of LIP among C/EBPβ isoforms increase. Consistent with a role in PRB expression, in vivo C/EBPβ and PR isoform A expression showed mutually exclusive localization in mammary epithelium, while C/EBPβ and PRB largely co-localized. We suggest a critical role for C/EBPβ, particularly LIP, in PRB expression.

The study of the biology and function of B cells, or the dissection and in vitro creation of enormous recombinant antibody repertoires, requires the isolation of large numbers of pure CD19+ B cells. The StraightFrom® Leukopak CD19 MicroBead Kit was recently introduced as a fast and robust kit to isolate human CD19+ B cells. This uses paramagnetic microbeads conjugated to high-affinity anti-CD19 monoclonal antibodies to bind B cells in leukapheresis (Leukopak) samples. The overall purity of the isolated cells, together with the characterization of the different CD19+ subclasses, was assessed by flow cytometry using a recombinant (REAffinity) antibody panel, revealing that the method allowed the recovery of over 93% of CD19+ B cells without any pre-purification step. This enables the relatively straightforward purification of all the circulating CD19+ B cells in a single donor.

Coronary microvascular dysfunction predicts and may be a proximate cause of cardiac dysfunction and mortality in diabetes; however, few effective treatments exist for these conditions. We recently demonstrated that mineralocorticoid receptor (MR) antagonism reversed cardiovascular dysfunction in early-stage obesity/insulin resistance. The mechanisms underlying this benefit of MR antagonism and its relevance in the setting of long-term obesity complications like diabetes; however, remain unclear. Thus, the present study evaluated the impact of MR antagonism on diabetes-related coronary dysfunction and defines the MR-dependent vascular transcriptome in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat recapitulating later stages of human diabetes. OLETF rats were treated with spironolactone (Sp) and compared to untreated OLETF and lean Long-Evans Tokushima Otsuka rats. Sp treatment attenuated diabetes-associated adipose and cardiac inflammation/fibrosis and improved coronary endothelium-dependent vasodilation but did not alter enhanced coronary vasoconstriction, blood pressure, or metabolic parameters in OLETF rats. Further mechanistic studies using RNA deep sequencing of OLETF rat aortas revealed 157 differentially expressed genes following Sp including upregulation of genes involved in the molecular regulation of nitric oxide bioavailability (Hsp90ab1, Ahsa1, Ahsa2) as well as novel changes in α1D adrenergic receptors (Adra1d), cyclooxygenase-2 (Ptgs2), and modulatory factors of these pathways (Ackr3, Acsl4). Further, Ingenuity Pathway Analysis predicted inhibition of upstream inflammatory regulators by Sp and inhibition of 'migration of endothelial cells', 'differentiation of smooth muscle', and 'angiogenesis' biological functions by Sp in diabetes. Thus, this study is the first to define the MR-dependent vascular transcriptome underlying treatment of diabetes-related coronary microvascular dysfunction by Sp.

The family 81 glycoside hydrolase (GH81) from Clostridium thermocellum is a β-1,3-glucanase belonging to cellulosomal complex. The gene encoding GH81 from Clostridium thermocellum (CtLam81A) was cloned and expressed displaying a molecular mass of ~82 kDa. CtLam81A showed maximum activity against laminarin (100 U/mg), followed by curdlan (65 U/mg), at pH 7.0 and 75 °C. CtLam81A displayed Km, 2.1 ± 0.12 mg/ml and Vmax, 109 ± 1.8 U/mg, against laminarin under optimized conditions. CtLam81A activity was significantly enhanced by Ca2+ or Mg2+ ions. Melting curve analysis of CtLam81A showed an increase in melting temperature from 91 °C to 96 °C by Ca2+ or Mg2+ ions and decreased to 82 °C by EDTA, indicating that Ca2+ and Mg2+ ions may be involved in catalysis and in maintaining structural integrity. TLC and MALDI-TOF analysis of β-1,3-glucan hydrolysed products released initially, showed β-1,3-glucan-oligosaccharides degree of polymerization (DP) from DP2 to DP7, confirming an endo-mode of action. The catalytically inactive mutant CtLam81A-E515A generated by site-directed mutagenesis was co-crystallized and tetragonal crystals diffracting up to 1.4 Å resolution were obtained. CtLam81A-E515A contained 15 α-helices and 38 β-strands forming a four-domain structure viz. a β-sandwich domain I at N-terminal, an α/β-domain II, an (α/α)6 barrel domain III, and a small 5-stranded β-sandwich domain IV.

Parkinson's disease (PD) is the second most common age-related neurodegenerative disease in the elderly and the patients suffer from uncontrolled movement disorders due to loss of dopaminergic (DA) neurons on substantia nigra pars compacta (SNpc). We previously reported that transplantation of human fetal midbrain-derived neural precursor cells restored the functional deficits of a 6-hydroxy dopamine (6-OHDA)-treated rodent model of PD but its low viability and ethical issues still remain to be solved. Albeit immune privilege and neural differentiation potentials suggest mesenchymal stem cells (MSCs) from various tissues including human placenta MSCs (hpMSCs) for an alternative source, our understanding of their therapeutic mechanisms is still limited. To expand our knowledge on the MSC-mediated PD treatment, we here investigated the therapeutic mechanism of hpMSCs and hpMSC-derived neural phenotype cells (hpNPCs) using a PD rat model. Whereas both hpMSCs and hpNPCs protected DA neurons in the SNpc at comparable levels, the hpNPC transplantation into 6-OHDA treated rats exhibited longer lasting recovery in motor deficits than either the saline or the hpMSC treated rats. The injected hpNPCs induced delta-like ligand (DLL)1 and neurotrophic factors, and influenced environments prone to neuroprotection. Compared with hpMSCs, co-cultured hpNPCs more efficiently protected primary neural precursor cells from midbrain against 6-OHDA as well as induced their differentiation into DA neurons. Further experiments with conditioned media from hpNPCs revealed that the secreted factors from hpNPCs modulated immune responses and neural protection. Taken together, both DLL1-mediated contact signals and paracrine factors play critical roles in hpNPC-mediated improvement. First showing here that hpMSCs and their neural derivative hpNPCs were able to restore the PD-associated deficits via dual mechanisms, neuroprotection and immunosuppression, this study expanded our knowledge of therapeutic mechanisms in PD and other age-related diseases.

Islet transplantation has been reported to restore normoglycemia and the overall metabolic control in type 1 diabetes mellitus (DM). In the most experienced centers, islet transplantation clinical outcome is similar to that of the whole pancreas transplantation. Long-term islet transplantation function remains a very interesting matter worth discussing. A progressive islet function decrease was reported, probably due to islet exhaustion. In 5 islet-transplanted patients with at least 3-yr follow-up and still insulin independent, their glycemic control was characterized by a blinded retrospective continuous glucose monitoring system (CGMS). Islet transplantation restored glycemic control and glucose variability. Data were compared with patients in the waiting list. All the parameters of glycemic variability tested had improved significantly in patients who had islet transplantation compared with those patients who were on the waiting list. In conclusion, islet transplantation is able to maintain a proper glucose control and normalize glycemic variability in selected patients. A blinded retrospective CGMS is a useful method to characterize glucose homeostasis deeply in vivo in islet-transplanted patients.

Alopecia areata (AA) is an autoimmune hair loss disease with infiltration of proinflammatory cells into hair follicles. Current therapeutic regimens are unsatisfactory mainly because of the potential for side effects and/or limited efficacy. Here we report that cultured, transduced fibroblasts, which express the immunomodulatory molecule indoleamine 2,3-dioxygenase (IDO), can be applied to prevent hair loss in an experimental AA model. A single intraperitoneal (IP) injection of IDO-expressing primary dermal fibroblasts was given to C3H/HeJ mice at the time of AA induction. While 60-70% of mice that received either control fibroblasts or vehicle injections developed extensive AA, none of the IDO-expressing fibroblast-treated mice showed new hair loss up to 20 weeks post injection. IDO cell therapy significantly reduced infiltration of CD4+ and CD8+ T cells into hair follicles and resulted in decreased expression of TNF-α, IFN-γ and IL-17 in the skin. Skin draining lymph nodes of IDO fibroblast-treated mice were significantly smaller, with more CD4+ CD25+ FoxP3+ regulatory T cells and fewer Th17 cells than those of control fibroblast and vehicle-injected mice. These findings indicate that IP injected IDO-expressing dermal fibroblasts can control inflammation and thereby prevent AA hair loss.

Clinical studies show that anxiety and chronic pain are concomitant. The neural basis for the comorbidity is unclear. The prefrontal cortex (PFC) has been recognized as a critical area for affective disorders and chronic pain modulation. In this study, we examined the role of the PFC in the pathogenesis of anxiety associated with chronic pain in a rat model of neuropathic pain with spare nerve injury (SNI). The SNI rats showed apparent anxiety-like behaviors in both open field (OF) test and elevated-plus maze (EPM) test eight weeks after surgery. Thus, the number of entries to the central area in the OF decreased to 45% (±5%, n = 15) of sham control (n = 17), while the overall motor activity (i.e., total distance) was unaffected. In the EPM, the percentage of entries into the open arms significantly (p < 0.001) decreased in SNI rats (SNI: 12.58 ± 2.7%, n = 15; sham: 30.75 ± 2.82%, n = 17), so did the time spent in the open arms (SNI: 4.35 ± 1.45%, n = 15; Sham: 11.65 ± 2.18%, n = 17). To explore the neural basis for the association between anxiety and chronic pain, local field potentials (LFPs) were recorded from the medial PFC (mPFC) and ventral hippocampus. In SNI rats, there were significantly greater increases in both theta-frequency power in the mPFC and theta-frequency synchronization between the mPFC and ventral hippocampus, when animals were displaying elevated anxiety-like behaviors in avoiding anxiogenic regions in EPM and OF chamber. Western blot analyses showed a significant elevation of serotonin transporter expression in the anxious SNI rats. Inhibition of serotonin transporter effectively alleviated anxiety-like behaviors following sub-chronic (15 days) treatment with systemic citalopram (10 mg/kg/day, intraperitoneally). Moreover, the anxiety-like behaviors in the SNI rats were also suppressed by direct mPFC application of serotonin. Taken together, we conclude that the plasticity of serotonin transmission in the mPFC likely contribute to the promotion of anxiety state associated with neuropathic pain.

Kudzu, Pueraria montana var. lobata, is a woody vine native to Southeast Asia that has been introduced globally for cattle forage and erosion control. The vine is highly invasive in its introduced areas, including the southeastern US. Modern molecular marker resources are limited for the species, despite its importance. Transcriptomes for P. montana var. lobata and a second phaseoloid legume taxon previously ascribed to genus Pueraria, Neustanthus phaseoloides, were generated and mined for microsatellites and single nucleotide polymorphisms.

Smoking is one of the most avoidable health risk factors, and yet the quitting success rates are low. The usage of tailored health messages to support quitting has been proved to increase quitting success rates. Technology can provide convenient means to deliver tailored health messages. Health recommender systems are information-filtering algorithms that can choose the most relevant health-related items-for instance, motivational messages aimed at smoking cessation-for each user based on his or her profile. The goals of this study are to analyze the perceived quality of an mHealth recommender system aimed at smoking cessation, and to assess the level of engagement with the messages delivered to users via this medium.

Avian β-defensins (AvBD) are cationic antimicrobial peptides (CAMP) with broad-spectrum antimicrobial activity, chemotactic property, and low host cytotoxicity. However, their bactericidal activity is greatly compromised under physiological salt concentrations which limits the use of these peptides as therapeutic agents. The length and the complex structure involving three conserved disulfide bridges are additional drawbacks associated with high production cost. In the present study, short linear CAMPs (11 to 25 a.a. residues) were developed based on the key functional components of AvBDs with additional modifications. Their biological functions were characterized.

The interaction between arbuscular mycorrhizal fungi (AMF) and AMF spore associated bacteria (SAB) were previously found to improve mycorrhizal symbiotic efficiency under saline stress, however, the information about the molecular basis of this interaction remain unknown. Therefore, the present study aimed to investigate the response of maize plants to co-inoculation of AMF and SAB under salinity stress.

Several type 2 diabetes (T2D) susceptibility loci identified via genome-wide association studies were found to be replicated among various populations. However, the influence of these loci on T2D in Thai population is unknown. The aim of this study was to investigate the influence of eight single nucleotide polymorphisms (SNPs) reported in GWA studies on T2D and related quantitative traits in Thai population.