How culture affects innovation in an organization

Both technology and innovation are considered major contributors to the competitiveness of companies and in exploiting opportunities in the market; however, too often the people processes are not given enough attention in transformation efforts - they are viewed as "HR processes" and technical leaders may not see the value of examining these areas early on as accelerators for change. The innovation culture framework presented in this paper is based on three thematic elements of innovation culture in organizations: Transformational Leadership, Organizational Climate / Environment, and Organizational Practices & Processes. The project tested and refined the framework by conducting a set of interviews, focus groups and workshop-based trials with participating commercial organizations. By focusing on the culture within an organization and coupling with other technology and innovation management efforts, leaders will have a more systemic understanding of how to sustain and increase the innovation capabilities of their organizations

The Effects of Physical Activity on Hepatic Lipid Metabolism During Weight-Loss

Non-alcoholic fatty liver disease (NAFLD) develops as a result of physical inactivity and overnutrition. Changing dietary behaviors and increasing physical activity are common strategies used for weight-loss; however, it remains unclear what additional benefits are provided by incorporating physical activity in a weight-loss program for the treatment of NAFLD. The purpose of this study was to determine how physical activity reduces hepatic steatosis and changes the expression of hepatic lipogenic genes during weight-loss. Male C57BL/6 mice were fed either a low-fat (LFD; 10% kcal fat) or high-fat (HFD; 60% kcal fat) diet for 10-weeks. Following 10-weeks, the HFD group was randomly assigned to either a LFD (Diet) or LFD with physical activity (Diet+PA) to induce weight-loss for 8-weeks. After 8-weeks of weight-loss, reductions in body and liver mass were observed in both Diet and Diet+PA groups (see Table 1.). Interestingly, the Diet+PA group lost significantly (P\u3c0.05) more body mass than the Diet group. Reductions in body mass and HOMA-IR in the Diet and Diet+PA groups were matched by reductions in hepatic triglyceride levels. In the Diet+PA group, liver triglyceride and cholesterol levels were significantly (P\u3c0.05) lower than all other groups. The greater reduction in hepatic triglyceride levels from physical activity was due to significant (P\u3c0.05) reductions in the expression of lipogenic FASN and SCD-1 mRNA. Interestingly, physical activity did not alter fatty acid uptake or fatty acid oxidation as observed with CD36 and CPT-1a mRNA levels, respectively. Based on these findings, the addition of physical activity to a diet-induced weight-loss intervention provides a more effective approach for the treatment of NAFLD than dieting alone. Table 1. Whole body and hepatic metabolic characteristics following weight-loss. Variables LFD (n=12) HFD (n=12) Diet (n=12) Diet+PA (n=12) Body mass (g) 30.2 ± 1.1 48.8 ± 0.5* 30.3 ± 0.7† 26.1 ± 0.3*,†,‡ Liver mass (g) 1.2 ± 0.1 2.9 ± 0.2* 1.2 ± 0.1† 1.2 ± 0.1† Triglyceride (mg/dL) 99.4 ± 8.7 96.7 ± 5.5 88.3 ± 6.1 88.4 ± 4.8 Cholesterol (mg/dL) 153.5 ± 10.1 246.0 ± 8.7* 148.2 ± 15.5† 127.6 ± 4.7*,† HOMA-IR 22.9 ± 1.2 187.3 ± 7.5* 19.4 ± 8.8† 25.3 ± 10.5† Liver Tg (mg/mg tissue) 1.18 ± 0.14 2.53 ± 0.05* 0.96 ± 0.15† 0.58 ± 0.07*,†,‡ Liver Chol (μg/mg tissue) 437.0 ± 43.0 585.2 ± 54.4* 527.0 ± 56.5 324.0 ± 27.3*,†,‡ FASN mRNA 1.00 ± 0.20 1.90 ± 0.34* 2.10 ± 0.54* 0.46 ± 0.11*,†,‡ CD36/FAT mRNA 1.00 ± 0.22 0.19 ± 0.20* 0.97 ± 0.10† 0.80 ± 0.04† SCD-1 mRNA 1.00 ± 0.28 1.94 ± 0.83* 0.76 ± 0.13† 0.44 ± 0.05*,†,‡ CPT-1a mRNA 1.00 ± 0.18 0.74 ± 0.04* 0.62 ± 0.08* 0.73 ± 0.05* Note. Data are presented as mean ± SEM.*Significantly (P\u3c0.05) different than LFD; †significantly (P\u3c0.05) different than HFD; ‡significantly (P\u3c0.05) different than Diet

The Effects of Physical Activity on Markers of Hepatic Inflammation During Weight-Loss

Non-alcoholic fatty liver disease (NAFLD) represents a continuum that begins with accumulation of lipid in hepatic cells progressing to hepatic steatosis with inflammation (steatohepatitis), fibrosis, and cirrhosis. Weight-loss using dietary modification and physical activity are common strategies used for the treatment of NAFLD; however, it remains to be determined the effects of physical activity on hepatic inflammation during weight-loss. The purpose of this study was to determine the therapeutic role of physical activity on plasma and hepatic inflammatory markers during weight-loss. Male C57BL/6 mice were fed either a low-fat (LFD; 10% kcal fat) or high-fat (HFD; 60% kcal fat) diet for 10-weeks. Following 10-weeks, the HFD group was randomly assigned to either a LFD (Diet) or LFD with physical activity (Diet+PA) to induce weight loss for 8-weeks. After 8-weeks, reductions in body mass were observed in both Diet and Diet+PA groups (see Table 1.). Interestingly, the Diet+PA group lost significantly (P\u3c0.05) more body mass than the Diet group. Despite significant (P\u3c0.05) reductions in body mass and HOMA-IR, plasma TNF-α remained elevated in the Diet and Diet+PA groups. Moreover, Diet+PA plasma TNF-α was significantly (P\u3c0.05) greater than the HFD obese controls. Elevated plasma TNF-α in the Diet+PA was matched by a greater hepatic expression of IL-1β and IL-6 mRNA when compared to all groups. Interestingly, the expression of TGF-β1 mRNA was significantly (P\u3c0.05) reduced in the Diet+PA when compared to all groups. The elevated plasma TNF-α and expression of IL-1β and IL-6 mRNA are likely due to physical activity. It remains unclear as to the pro-inflammatory effects of physical activity during weight-loss; however, this may be part of a protective adaption to regular exercise. Furthermore, the reduced hepatic TGF-β1 mRNA levels suggest a protective strategy against fibrogenesis in the spectrum of liver disease. Table 1. Whole body and hepatic metabolic characteristics following weight-loss. Variables LFD (n=12) HFD (n=12) Diet (n=12) Diet+PA (n=12) Body mass (g) 30.2 ± 1.1 48.8 ± 0.5* 30.3 ± 0.7† 26.1 ± 0.3*,†,‡ HOMA-IR 22.9 ± 1.2 187.3 ± 7.5* 19.4 ± 8.8† 25.3 ± 10.5† IL-6 (pg/mL) 6.4 ± 0.7 6.2 ± 1.0 5.9 ± 0.9 6.4 ± 0.9 TNF-α (pg/mL) 30.8 ± 6.7 60.6 ± 5.3* 74.0 ± 8.1* 82.5 ± 7.7*,† IL-1β mRNA 1.00 ± 0.51 0.97 ± 0.34 1.20 ± 0.59 2.83 ± 0.62*,†,‡ IL-6 mRNA 1.00 ± 0.45 1.53 ± 0.50 1.16 ± 0.72 2.36 ± 0.55*,†,‡ TNF-α mRNA 1.00 ± 0.09 0.89 ± 0.08 0.94 ± 0.14 0.83 ± 0.06 TGF-β1 mRNA 1.00 ± 0.06 1.02 ± 0.06 1.02 ± 0.10 0.84 ± 0.05† Note. Data are presented as mean ± SEM. *Significantly (P\u3c0.05) different than LFD; †significantly (P\u3c0.05) different than HFD; ‡significantly (P\u3c0.05) different than Diet

Structure of the γ-D-glutamyl-L-diamino acid endopeptidase YkfC from Bacillus cereus in complex with L-Ala-γ-D-Glu: insights into substrate recognition by NlpC/P60 cysteine peptidases.

Dipeptidyl-peptidase VI from Bacillus sphaericus and YkfC from Bacillus subtilis have both previously been characterized as highly specific γ-D-glutamyl-L-diamino acid endopeptidases. The crystal structure of a YkfC ortholog from Bacillus cereus (BcYkfC) at 1.8 Å resolution revealed that it contains two N-terminal bacterial SH3 (SH3b) domains in addition to the C-terminal catalytic NlpC/P60 domain that is ubiquitous in the very large family of cell-wall-related cysteine peptidases. A bound reaction product (L-Ala-γ-D-Glu) enabled the identification of conserved sequence and structural signatures for recognition of L-Ala and γ-D-Glu and, therefore, provides a clear framework for understanding the substrate specificity observed in dipeptidyl-peptidase VI, YkfC and other NlpC/P60 domains in general. The first SH3b domain plays an important role in defining substrate specificity by contributing to the formation of the active site, such that only murein peptides with a free N-terminal alanine are allowed. A conserved tyrosine in the SH3b domain of the YkfC subfamily is correlated with the presence of a conserved acidic residue in the NlpC/P60 domain and both residues interact with the free amine group of the alanine. This structural feature allows the definition of a subfamily of NlpC/P60 enzymes with the same N-terminal substrate requirements, including a previously characterized cyanobacterial L-alanine-γ-D-glutamate endopeptidase that contains the two key components (an NlpC/P60 domain attached to an SH3b domain) for assembly of a YkfC-like active site

The structure of BVU2987 from Bacteroides vulgatus reveals a superfamily of bacterial periplasmic proteins with possible inhibitory function.

Proteins that contain the DUF2874 domain constitute a new Pfam family PF11396. Members of this family have predominantly been identified in microbes found in the human gut and oral cavity. The crystal structure of one member of this family, BVU2987 from Bacteroides vulgatus, has been determined, revealing a β-lactamase inhibitor protein-like structure with a tandem repeat of domains. Sequence analysis and structural comparisons reveal that BVU2987 and other DUF2874 proteins are related to β-lactamase inhibitor protein, PepSY and SmpA_OmlA proteins and hence are likely to function as inhibitory proteins

Structures of three members of Pfam PF02663 (FmdE) implicated in microbial methanogenesis reveal a conserved α+β core domain and an auxiliary C-terminal treble-clef zinc finger

The first structures from the FmdE Pfam family (PF02663) reveal that some members of this family form tightly intertwined dimers consisting of two domains (N-terminal α+β core and C-terminal zinc-finger domains), whereas others contain only the core domain. The presence of the zinc-finger domain suggests that some members of this family may perform functions associated with transcriptional regulation, protein–protein interaction, RNA binding or metal-ion sensing

Structure of a membrane-attack complex/perforin (MACPF) family protein from the human gut symbiont Bacteroides thetaiotaomicron

The crystal structure of a novel MACPF protein, which may play a role in the adaptation of commensal bacteria to host environments in the human gut, was determined and analyzed

Structure of Bacteroides thetaiotaomicron BT2081 at 2.05 Å resolution: the first structural representative of a new protein family that may play a role in carbohydrate metabolism

The crystal structure of BT2081 from B. thetaiotaomicron reveals a two-domain protein with a putative carbohydrate-binding site in the C-­terminal domain

A conserved fold for fimbrial components revealed by the crystal structure of a putative fimbrial assembly protein (BT1062) from Bacteroides thetaiotaomicron at 2.2 Å resolution

The crystal structure of BT1062 from Bacteroides thetaiotaomicron revealed a conserved fold that is widely adopted by fimbrial components

The structure of KPN03535 (gi|152972051), a novel putative lipoprotein from Klebsiella pneumoniae, reveals an OB-fold

KPN03535 is a protein unique to K. pneumoniae. The crystal structure reveals that KPN03535 represents a novel variant of the OB-fold and is likely to be a DNA-binding lipoprotein