Miracle-dz/UniFAR-FTUs huggingface dataset:
Arginine specific aminopeptidase from Lactobacillus brevis

ABSTRACT The proteolytic system of lactic acid bacteria contribute to the development of flavor during the ripening of cheese through the generation of short peptides and free amino acids, which directly or indirectly act as flavor precursors. Newly isolated lactic acid bacteria (LAB) as well as those procured from culture collection centers were screened for the production of various substrate specific aminopeptidases. Among all the strains screened, L. brevis (NRRL B-1836) was found to produce quantifiable amount of intracellular arginine specific aminopeptidase (EC 3.4.11.6). The productivity of arginine aminopeptidase in 5 L fermentor was 36 IU/L/h. The Luedeking and Piret model was tested for intracellular production of aminopeptidase and the data seemed to fit well, as the correlation coefficient was 0.9964 for MRS. The α AP and β AP was 0.4865 and 0.0046, respectively in MRS medium indicating that the yield was predominantly depended on growth. The culture produced lactic acid and also tolerated pH 2.0-3.0 and 0.3-0.5% bile salts, the most important probiotic features. Key words : Lactobacillus brevis, aminopeptidases, arginine- p- nitroanilide
Cousinia kermanensis and C. pulcherantha spp. nov. (Compositae, sect. Congestae and sect. Leiocaules) from southeastern Iran

Cousinia kermanensis sp. nov. (sect. Congestae Bunge) and C. pulcherantha sp. nov. (sect. Leiocaules Bunge) are described from Kerman in southeastern Iran. These species are compared to their closest related species, C. decurrens Regel and C. oophora Rech. f. , respectively. The habitat of C. kermanensis is lowland mountains or hills with poor soils inside the steppe of Artemisia sieberi Besser. Cousinia pulcherantha grows on highland slopes of mountains with deep soils inside the steppe of Artemisia aucheri Boiss. Illustrations of the new species are presented.
Family Ties and Aging in a Multiethnic Cohort

Objective: Lack of social support is linked to lower cognitive function and cognitive decline. We investigated the effects of a specific type of social relationship, family ties, on cognitive trajectories in non-Hispanic whites, non-Hispanic blacks, and Hispanics. Methods: Using multiple-group latent growth curve models, we analyzed associations between the number of children/grandchildren/siblings/other relatives contacted within the past month at baseline and cognitive trajectories in 1420 older adults who were nondemented at baseline. Language, memory, and visuospatial abilities were assessed at baseline and at 18- and 24-month follow-ups for up to six visits. Inferential analyses assessed the differential effects of sex/gender and race/ethnicity for each family tie. Results: Independent of all covariates, contact with more relatives was associated with better initial memory (b = .01) and language functioning (b = .01) across race/ethnicity and sex/gender. Conclusion: The size of peripheral rather than immediate family networks may be more likely to affect cognitive function in older adults.
Regulation of Sulfur Nutrition in Wild-Type and Transgenic Poplar Over-Expressing g-Glutamylcysteine Synthetase in the Cytosol as Affected by

This study with poplar (Populus tremula 3 Populus alba) cuttings was aimed to test the hypothesis that sulfate uptake is regulated by demand-driven control and that this regulation is mediated by phloem-transported glutathione as a shoot-toroot signal. Therefore, sulfur nutrition was investigated at (a) enhanced sulfate demand in transgenic poplar over-expressing g-glutamylcysteine (g-EC) synthetase in the cytosol and (b) reduced sulfate demand during short-term exposure to H2S. H2S taken up by the leaves increased cysteine, g-EC, and glutathione concentrations in leaves, xylem sap, phloem exudate, and roots, both in wild-type and transgenic poplar. The observed reduced xylem loading of sulfate after H2S exposure of wild-type poplar could well be explained by a higher glutathione concentration in the phloem. In transgenic poplar increased concentrations of glutathione and g-EC were found not only in leaves, xylem sap, and roots but also in phloem exudate irrespective of H2S exposure. Despite enhanced phloem allocation of glutathione and its accumulation in the roots, sulfate uptake was strongly enhanced. This finding is contradictory to the hypothesis that glutathione allocated in the phloem reduces sulfate uptake and its transport to the shoot. Correlation analysis provided circumstantial evidence that the sulfate to glutathione ratio in the phloem may control sulfate uptake and loading into the xylem, both when the sulfate demand of the shoot is increased and when it is reduced. Sulfur ranks fifth or sixth by quantity of nutrient elements in plants (Cram, 1990). In its reduced form, i.e. in the oxidation state-II, sulfur is mainly found as a structural and functional component of proteins. Sulfur is mostly available to plants in the oxidized form of sulfate in the soils and must thus be reduced and assimilated into the sulfur-containing amino acids Cys and Met to fulfil requirements of protein synthesis. The processes of both reduction and assimilation are often restricted to mature leaves (Brunold, 1990), but especially in trees, considerable reduction and assimilation may also occur in the roots. The supply of stem tissues and young developing leaves with reduced sulfur from assimilatory sulfate reduction in the roots is particularly notable in trees (Herschbach and Rennenberg, 1997). Sulfate supply at the whole plant level may be controlled by regulation of sulfate uptake by the roots whereas the supply to the shoot may be determined by xylem loading of sulfate in the root. In
A recombinant Escherichia coli expressing an α-alkyl-β-ketoester reductase with unusual stereoselectivity

A recombinant Escherichia coli expressing an α-alkyl-β-ketoester reductase that yields the anti (2R,3R) α-alkyl-β-hydroxyester as the major product was constructed. The enzyme was identified from genomic libraries of Paucimonas lemoignei, cloned and expressed in E. coli providing a whole cell biocatalyst with novel stereoselectivity. This constitutes the first report on a whole cell biocatalyst for the synthesis of (2R,3R) α-alkyl-β-hydroxy-esters.
Human Fallopian Tube Epithelial Cell Culture Model To Study Host Responses to Chlamydia trachomatis Infection

Chlamydia trachomatis infection of the human fallopian tubes can lead to damaging inflammation and scarring, ultimately resulting in infertility. To study the human cellular responses to chlamydial infection, researchers have frequently used transformed cell lines that can have limited translational relevance. We developed a primary human fallopian tube epithelial cell model based on a method previously established for culture of primary human bronchial epithelial cells. After protease digestion and physical dissociation of excised fallopian tubes, epithelial cell precursors were expanded in growth factor-containing medium. ABSTRACT Chlamydia trachomatis infection of the human fallopian tubes can lead to damaging inflammation and scarring, ultimately resulting in infertility. To study the human cellular responses to chlamydial infection, researchers have frequently used transformed cell lines that can have limited translational relevance. We developed a primary human fallopian tube epithelial cell model based on a method previously established for culture of primary human bronchial epithelial cells. After protease digestion and physical dissociation of excised fallopian tubes, epithelial cell precursors were expanded in growth factor-containing medium. Expanded cells were cryopreserved to generate a biobank of cells from multiple donors and cultured at an air-liquid interface. Culture conditions stimulated cellular differentiation into polarized mucin-secreting and multiciliated cells, recapitulating the architecture of human fallopian tube epithelium. The polarized and differentiated cells were infected with a clinical isolate of C. trachomatis, and inclusions containing chlamydial developmental forms were visualized by fluorescence and electron microscopy. Apical secretions from infected cells contained increased amounts of proteins associated with chlamydial growth and replication, including transferrin receptor protein 1, the amino acid transporters SLC3A2 and SLC1A5, and the T-cell chemoattractants CXCL10, CXCL11, and RANTES. Flow cytometry revealed that chlamydial infection induced cell surface expression of T-cell homing and activation proteins, including ICAM-1, VCAM-1, HLA class I and II, and interferon gamma receptor. This human fallopian tube epithelial cell culture model is an important tool with translational potential for studying cellular responses to Chlamydia and other sexually transmitted pathogens.
Early Onset of Sex-Dependent Mitochondrial Deficits in the Cortex of 3xTg Alzheimer’s Mice

Alzheimer’s disease (AD) is a major public health concern worldwide. Advanced age and female sex are two of the most prominent risk factors for AD. AD is characterized by progressive neuronal loss, especially in the cortex and hippocampus, and mitochondrial dysfunction has been proposed to be an early event in the onset and progression of the disease. Our results showed early perturbations in mitochondrial function in 3xTg mouse brain, with the cortex being more susceptible to mitochondrial changes than the hippocampus. In the cortex of 3xTg females, decreased coupled and uncoupled respiration were evident early (at 2 months of age), while in males it appeared later at 6 months of age. We observed increased coupled respiration in the hippocampus of 2-month-old 3xTg females, but no changes were detected later in life. Changes in mitochondrial dynamics were indicated by decreased mitofusin (Mfn2) and increased dynamin related protein 1 (Drp1) (only in females) in the hippocampus and cortex of 3xTg mice. Our findings highlight the importance of controlling and accounting for sex, brain region, and age in studies examining brain bioenergetics using this common AD model in order to more accurately evaluate potential therapies and improve the sex-specific translatability of preclinical findings.
The Effects of Performing Mental Exertion during Cycling Exercise on Fatigue Indices

Abstract This study investigated the effect of performing prolonged mental exertion during submaximal cycling exercise on exercise tolerance and fatigue. Participants performed 5 experimental sessions. Session 1: determination of cycling peak power output. Sessions 2 and 3: cycling to exhaustion at 65% peak power output with mental exertion or watching a movie. Sessions 4 and 5: cycling for 45 min at 65% peak power output with mental exertion or while watching a movie. During sessions 2–5, rate of perceived exertion and heart rate were recorded while cycling and cortisol and prolactin concentrations, psychomotor vigilance task performance, and maximal voluntary contraction were measured pre-and post-sessions. During sessions 2 and 3, time to exhaustion was reduced (p<0.01) and rate of perceived exertion was increased (p<0.01) in session 2 compared to 3. Cortisol, prolactin and heart rate increased and psychomotor vigilance task and maximal voluntary contraction decreased from pre-to post-sessions with no difference between sessions. Cortisol, prolactin and rate of perceived exertion were higher (p<0.03) in session 4 than 5. Heart rate increased and maximal voluntary contraction decreased from pre-to post-sessions with no difference between sessions. Prolonged mental exertion during cycling exercise reduces exercise tolerance, which appears to be mediated psychologically rather than physiologically.
Proximal threats promote enhanced acquisition and persistence of reactive fear-learning circuits

Significance Traditional laboratory-based fear-conditioning approaches are often limited in their generalizability to real-world encounters where threats are dynamic and embedded in contextually rich environments. Moreover, while spatial distance to a threat organizes defensive responses, our understanding of the neurobehavioral mechanisms relating proximity and fear learning is lacking. To address these limitations, we developed a three-dimensional (3D) virtual reality simulation that provides a more ecologically valid examination of how threat proximity influences the learning and memory of fear associations. Our findings highlight that threats invading peripersonal space persist longer in memory and uniquely recruit a reactive neural fear system, which has important clinical implications for understanding how near-body traumatic experiences exacerbate the development of traumatic stress disorders. Physical proximity to a traumatic event increases the severity of accompanying stress symptoms, an effect that is reminiscent of evolutionarily configured fear responses based on threat imminence. Despite being widely adopted as a model system for stress and anxiety disorders, fear-conditioning research has not yet characterized how threat proximity impacts the mechanisms of fear acquisition and extinction in the human brain. We used three-dimensional (3D) virtual reality technology to manipulate the egocentric distance of conspecific threats while healthy adult participants navigated virtual worlds during functional magnetic resonance imaging (fMRI). Consistent with theoretical predictions, proximal threats enhanced fear acquisition by shifting conditioned learning from cognitive to reactive fear circuits in the brain and reducing amygdala–cortical connectivity during both fear acquisition and extinction. With an analysis of representational pattern similarity between the acquisition and extinction phases, we further demonstrate that proximal threats impaired extinction efficacy via persistent multivariate representations of conditioned learning in the cerebellum, which predicted susceptibility to later fear reinstatement. These results show that conditioned threats encountered in close proximity are more resistant to extinction learning and suggest that the canonical neural circuitry typically associated with fear learning requires additional consideration of a more reactive neural fear system to fully account for this effect.
Structural basis for the broad substrate specificity of two acyl-CoA dehydrogenases FadE5 from mycobacteria

Significance The lipid content accounts for approximately 60% of the dry weight of the cell wall of pathogenic mycobacteria with Mycobacterium tuberculosis having more than 250 genes involved in fatty acid metabolism. Previous studies have shown that acyl-CoA dehydrogenase (ACD), which introduces unsaturation into fatty acids, exhibits strict substrate specificity toward different CoA thioester groups. Here, we identified a unique ACD member in mycobacteria that exhibits broad substrate specificity. Furthermore, we determined crystal structures of the enzyme and enzyme–substrate complexes to explain the broad substrate recognition observed in this system. Given the importance of FadE5 in fatty acid metabolism, these new structures are excellent platforms for rational structure based antituberculosis drug discovery. FadE, an acyl-CoA dehydrogenase, introduces unsaturation to carbon chains in lipid metabolism pathways. Here, we report that FadE5 from Mycobacterium tuberculosis (MtbFadE5) and Mycobacterium smegmatis (MsFadE5) play roles in drug resistance and exhibit broad specificity for linear acyl-CoA substrates but have a preference for those with long carbon chains. Here, the structures of MsFadE5 and MtbFadE5, in the presence and absence of substrates, have been determined. These reveal the molecular basis for the broad substrate specificity of these enzymes. FadE5 interacts with the CoA region of the substrate through a large number of hydrogen bonds and an unusual π–π stacking interaction, allowing these enzymes to accept both short- and long-chain substrates. Residues in the substrate binding cavity reorient their side chains to accommodate substrates of various lengths. Longer carbon-chain substrates make more numerous hydrophobic interactions with the enzyme compared with the shorter-chain substrates, resulting in a preference for this type of substrate.
The role of service-based learning in medical student education

We have read with great interest the article by Tanna et al on service-based learning at Imperial College London [1]. As medical students at King’s College London, we contribute our thoughts. The term ‘service-learning’ was a new concept for us. However, on reflection, we see similar parallels within our curriculum. In particular, our early years' longitudinal general practice placements encourage continuity and repeated supervised exposure to the same patients. A final year rotation then follows where we take on the role of a General Practitioner (GP). This involved making patient care package plans and home visits regulated and followed up by the GP. Regarding the increase of responsibility taken on through service learning, we have found evidence in medical education to support this claim. It shows servicelearning increased recognition of the importance of the role played in community health interventions. Consequently, this led to better engagement from students to attend their placement and incentivised their learning as opposed to passive learning [2]. We can validate this as having increased responsibility in our GP placements boosted engagement and clinical learning. The role of supervision has an important role in facilitating service-learning in medical education. We found training experiences were enhanced for medical students that had the support of the clinical teams on their placements. This included the whole practice staff acting synergistically together which improved satisfaction amongst supervisors and students [3]. Similarly, this applies outside primary care, where we have encountered a better learning experience when supported by the multi-disciplinary team. Tanna et al raise many valuable points regarding service learning. From the feedback received, there is definitely scope for greater exploration. It would be interesting to see the long-term benefits across a larger sample size using quantitative analysis. Along with its successful application in general practice, there may be an exciting potential in other clinical teaching settings. Yours sincerely
Investigating agreement between different data sources using Bayesian state-space models: an application to estimating NE Atlantic mackerel catch and stock abundance

Bayesian Markov chain Monte Carlo methods are ideally suited to analyses of situations where there are a variety of data sources, particularly where the uncertainties differ markedly among the data and the estimated parameters can be correlated. The example of Northeast Atlantic (NEA) mackerel is used to evaluate the agreement between available data from egg surveys, tagging, and catch-at-age using multiple models within the Bayesian framework WINBUGS. The errors in each source of information are dealt with independently, and there is extensive exploration of potential sources of uncertainty in both the data and the model. Model options include variation by age and over time of both selectivity in the fishery and natural mortality, varying the precision and calculation method for spawning-stock biomass derived from an egg survey, and the extent of missing catches varying over time. The models are compared through deviance information criterion and Bayesian posterior predictive p-values. To reconcile mortality estimated from the different datasets the landings and discards reported would have to have been between 1.7 and 3.6 times higher than the recorded catches.
Cavitation and cetacean

Bubbles are the most acoustically active naturally occurring entities in the ocean, and cetaceans are the most intelligent. Having evolved over tens of millions of years to cope with the underwater acoustic environment, cetaceans may have developed techniques from which we could learn. This paper outlines some of the possible interactions, ranging from the exploitation of acoustics in bubble nets to trap prey, to techniques for echolocating in bubbly water, to the possibility that man-made sonar signals could be responsible for bubble generation and death within cetaceans.
Hypericin Accumulation as a Determinant of PDT Efficacy

Efficacy of photodynamic therapy (PDT) with hypericin was compared using two cell lines in monolayer culture. Photokilling was substantially impaired in the A549 (human‐derived lung tumor) when compared with the 1c1c7 murine hepatoma. The efficacy of PDT with regard to photokilling was correlated with the steady‐state intracellular hypericin concentration. There was otherwise no difference in subcellular targets or the pathway to cell death: paraptosis. In a prior study involving cell lines derived from patients with head and neck cancer, differences in response to PDT had shown no correlation with photosensitizer uptake.
MYCOHERBICIDAL POTENTIAL OF ALTERNARIA ALTERNATA ITCC4896 FOR THE CONTROL OF PARTHENIUM HYSTEROPHORUS

Mycoherbicides are special biotechnology products which contain fungi or fungal metabo- lites as nonchemical alternatives thereby reducing the input of harmful chemicals to control noxious weeds. The present communication emphasizes on the potential of an indigenous isolate of Alternaria alternata ITCC 4896 as a mycoherbicide for the global weed - Parthenium hysterophorus. Of the various spore concentrations tested by in vitro Detached Leaf Bioassay, 1x10 6 spores/ml was the most effective inducing 89.2% leaf area damage on the 7th day and was further tested by Whole Plant Bioassay. Both in vitro Detached Leaf Bioassay and Whole Plant Bioassay exhibited a similar trend in disease devel- opment showing 50% damage at 96 hours post treatment. However, 100% mortality was observed in the Whole Plant Bioassay on the 7th day. This is the very first report on the bioweedicidal potential of A. alternata ITCC 4896 (LC#508) for use as a mycoherbicide for P. hysterophorus.
Herpes Simplex Virus Type 1 ICP27-Dependent Activation of NF-κB

ABSTRACT The ability of herpes simplex virus type 1 (HSV-1) to activate NF-κB has been well documented. Beginning at 3 to 5 h postinfection, HSV-1 induces a robust and persistent nuclear translocation of an NF-κB-dependent (p50/p65 heterodimer) DNA binding activity, as measured by electrophoretic mobility shift assay. Activation requires virus binding and entry, as well as de novo infected-cell protein synthesis, and is accompanied by loss of both IκBα and IκBβ. In this study, we identified loss of IκBα as a marker of NF-κB activation, and infection with mutants with individual immediate-early (IE) regulatory proteins deleted indicated that ICP27 was necessary for IκBα loss. Analysis of both N-terminal and C-terminal mutants of ICP27 identified the region from amino acids 21 to 63 as being necessary for IκBα loss. Additional experiments with mutant viruses with combinations of IE genes deleted revealed that the ICP27-dependent mechanism of NF-κB activation may be augmented by functional ICP4. We also analyzed two additional markers for NF-κB activation, phosphorylation of the p65 subunit on Ser276 and Ser536. Phosphorylation of both serines was induced upon HSV infection and required functional ICP4 and ICP27. Pharmacological inhibitor studies revealed that both IκBα and Ser276 phosphorylation were dependent on Jun N-terminal protein kinase activity, while Ser536 phosphorylation was not affected during inhibitor treatment. These results demonstrate that there are several layers of regulation of NF-κB activation during HSV infection, highlighting the important role that NF-κB may play in infection.