Solubility, (micro)structure, and in vitro digestion of pea protein dispersions as affected by high pressure homogenization and environmental conditions.

In this work, dispersions were prepared with commercial pea protein isolate (PPI) and subjected to different (i) high pressure homogenization (HPH) intensities (0 - 200 MPa) (room temperature, pH 7) or (ii) environmental conditions (60 °C, pH 7 or pH 12) to generate dispersions with distinct protein molecular and microstructural characteristics, impacting protein solubility. Besides, protein digestion was analyzed following the static INFOGEST in vitro digestion protocol. Generally, increasing pressure of the homogenization treatment was linked with decreasing particle sizes and enhanced protein digestion. More specifically, the dispersion that did not undergo HPH (0 MPa) as well as the dispersion treated at 60 °C, pH 7, had highly similar microstructures, consisting of large irregular particles (10 - 500 µm) with shell-like structures, and exhibited low solubility (around 15 % and 28 %, respectively), which resulted in limited proteolysis (35 % and 42 %, respectively). In contrast, the dispersion subjected to HPH at 100 MPa and the dispersion treated at 60 °C, pH 12 also had similar microstructures with small and homogeneous particles (<1 µm), and exhibited relatively good solubility (54 % and 31 %, respectively), which led to enhanced protein digestion levels (87 % and 74 %, respectively). This study highlights the potential of food processing on macronutrient (micro)structure and further gastrointestinal stability and functionality.

Descriptive epidemiology of smothering in Australian commercial free-range layer hen farms.

Since the early 2000 s the practice of free-range egg production has increased in developed countries, partly driven by consumer perception that free-range housing is better for hen welfare. While poultry in free-range systems have more behavioural opportunities compared with poultry in caged systems, free-range systems are associated with greater frequencies of infectious disease, predation and 'smothering', a condition where birds pile on top of one another with death occurring due to suffocation. Although the frequency of smothering deaths in Australian free-range layer poultry is anecdotally high, there is a lack of empirical evidence quantifying smothering cause-specific mortality rates and identifying factors that place birds at higher risk of death from smothering. This was a prospective cohort study of poultry flocks managed by three commercial free-range layer organisations in Eastern Australia. Flocks were enrolled into the study from 1 January 2019 to 29 March 2021 and were followed until the end of lay or until the end of the study on 31 March 2022, whichever occurred first. Throughout the follow-up period flock managers provided production details for each flock and details of smothering events using custom-designed logbooks.A total of 84 flocks were enrolled in the study: 32 from Organisation 1, 35 from Organisation 2 and 17 from Organisation 3. The number of birds per flock ranged from 16,000 to 45,000. The total mortality rate was 1131 deaths per 10,000 bird-years. Smothering mortality rate across the three organisations was 183 (minimum 133, maximum 223) deaths per 10,000 bird-years at risk. Smothering accounted for around 16% (minimum 9%, maximum 22%) of all deaths.We identified no distinctive temporal pattern in daily smothering risk as a function of either the number of days since placement or calendar date. The locations of smothering events in sheds and in the outdoor range were not consistent, with relatively large numbers of smothering events occurring in specific locations for some sheds but not others. To the best of our knowledge, this study is the largest prospective study of smothering mortality in commercial free-range layer flocks conducted to date. Estimates of smothering incidence rate and how that varies within and between flocks and organisations over time provides a critically important benchmark for further investigations into this substantial area of productivity loss.

Complete Genome Sequence of Pasteurella multocida Sequence Type 394, Isolated from a Case of Bovine Respiratory Disease in Australia.

Here, we present the completely closed genome sequence of Pasteurella multocida 17BRD-035, a bovine respiratory disease (BRD) pathogen from Queensland, Australia, with genes that confer resistance to ß-lactams, tilmicosin, and tetracycline. It consists of a single 2,624,884-bp chromosome and an average GC content of 40.23% and belongs to the newly described Rural Industries Research and Development Corporation (RIRDC) sequence type 394.

First Observation of Multiple Transverse Wobbling Bands of Different Kinds in

We report the first observation of two wobbling bands in ^{183}Au, both of which were interpreted as the transverse wobbling (TW) band but with different behavior of their wobbling energies as a function of spin. It increases (decreases) with spin for the positive (negative) parity configuration. The crucial evidence for the wobbling nature of the bands, dominance of the E2 component in the ΔI=1 transitions between the partner bands, is provided by the simultaneous measurements of directional correlation from the oriented states ratio and the linear polarization of the γ rays. Particle rotor model calculations with triaxial deformation reproduce the experimental data well. A value of spin, I_{m}, has been determined for the observed TW bands below which the wobbling energy increases and above which it decreases with spin. The nucleus ^{183}Au is, so far, the only nucleus in which both the increasing and the decreasing parts are observed and thus gives the experimental evidence of the complete transverse wobbling phenomenon.

Shape Coexistence at Zero Spin in

The low-spin structure of the semimagic ^{64}Ni nucleus has been considerably expanded: combining four experiments, several 0^{+} and 2^{+} excited states were identified below 4.5 MeV, and their properties established. The Monte Carlo shell model accounts for the results and unveils an unexpectedly complex landscape of coexisting shapes: a prolate 0^{+} excitation is located at a surprisingly high energy (3463 keV), with a collective 2^{+} state 286 keV above it, the first such observation in Ni isotopes. The evolution in excitation energy of the prolate minimum across the neutron N=40 subshell gap highlights the impact of the monopole interaction and its variation in strength with N.

Evidence for Rigid Triaxial Deformation in

An extensive, model-independent analysis of the nature of triaxial deformation in ^{76}Ge, a candidate for neutrinoless double-beta (0νßß) decay, was carried out following multistep Coulomb excitation. Shape parameters deduced on the basis of a rotational-invariant sum-rule analysis provided considerable insight into the underlying collectivity of the ground-state and γ bands. Both sequences were determined to be characterized by the same ß and γ deformation parameter values. In addition, compelling evidence for low-spin, rigid triaxial deformation in ^{76}Ge was obtained for the first time from the analysis of the statistical fluctuations of the quadrupole asymmetry deduced from the measured E2 matrix elements. These newly determined shape parameters are important input and constraints for calculations aimed at providing, with suitable accuracy, the nuclear matrix elements relevant to 0νßß.

Single Sitting Surgery for Concomitant Hydatid Cyst of Lung and Liver: A Case Report.

Hydatid disease is one of the diseases that have been discovered in the ancient times. Liver and lung are the most commonly affected organs, though it can involve any organs. Hydatid disease involving both the liver and the lung is reported about 10% of the cases. Here we report a case of 34 year old male presented with upper abdominal pain and intermittent fever for 3 months admitted in October 2016. His chest radiograph and computed tomography scan revealed large cystic lesion at right lung and another similar large lesion in the right lobe of liver. Echinococcus antibody was found positive. We treated him surgically. Histopathology reports confirmed concomitant hydatid cyst of both the lung and the liver.

Solid Pseudopapillary Tumor of the Pancreas: A Case Report.

Solid pseudopapillary tumors (SPT) of the pancreas are rare neoplasms of the pancreas accounting for only 1-2% of all pancreatic neoplasms, often detected initially on imaging. Its histogenesis is still uncertain and it has a low-grade malignant potential but excellent post-surgical curative rates and rare metastasis. Pathological and/or cytological evaluation still remains the gold standard in reaching a definitive diagnosis. It occurs most commonly in young females. We report a case of solid pseudopapillary tumor in the head of the pancreas in a 20 years old female admitted in Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh on 5th December 2015. Whipple's operation was done as a definitive treatment.

Incidence of contamination of live bird markets in Bangladesh with influenza A virus and subtypes H5, H7 and H9.

In the absence of robust active surveillance of avian influenza viruses (AIV) affecting poultry in South Asian countries, monitoring of live bird markets (LBMs) can be an alternative. In a longitudinal study of 32 LBM, five environments were sampled as follows: market floor, stall floor, slaughter area, poultry holding cage and water used for meat processing. Samples were taken monthly for 5 months, September 2013-January 2014. Incidence rates (IRs) of LBM contamination with AIV and its subtypes H5, H7 and H9 were assessed. In 10 of the LBM selected, biosecurity measures had been implemented through FAO interventions: the other 22 were non-intervened. Standard procedures were applied to detect AIV and three subtypes in pooled samples (1:5). An LBM was considered positive for AIV or a subtype if at least one of the pooled samples tested positive. The incidence rates of LBM contamination with AIV, H5, H7 and H9 were 0.194 (95% confidence interval (CI) 0.136-0.276), 0.031 (95% CI 0.013-0.075), 0 and 0.175 (95% CI 0.12-0.253) per LBM-month at risk, respectively. The log IR ratio between the FAO-intervened and non-intervened LBM for contamination with AIV was -0.329 (95% CI -1.052 to -0.394, p = .372), 0.598 (95% CI -1.593 to 2.789, p = .593) with subtype H5 and -0.500 (95% CI -1.249 to 0.248, p = .190) with subtype H9, indicating no significant difference. The results obtained suggest that both H5 and H9 were circulating in LBM in Bangladesh in the second half of 2013. The incidence of contamination with H9 was much higher than with H5.

Combination therapy strategies for improving PD-1 blockade efficacy: a new era in cancer immunotherapy.

Programmed death 1 (PD-1) is an immune checkpoint molecule that negatively regulates T-cell immune function through the interaction with its ligand PD-L1. Blockage of this interaction unleashes the immune system to fight cancer. Immunotherapy using PD-1 blockade has led to a paradigm shift in the field of cancer drug discovery, owing to its durable effect against a wide variety of cancers with limited adverse effects. A brief history and development of PD-1 blockade, from the initial discovery of PD-1 to the recent clinical output of this therapy, have been summarized here. Despite its tremendous clinical success rate over other cancer treatments, PD-1 blockade has its own pitfall; a significant fraction of patients remains unresponsive to this therapy. The key to improve the PD-1 blockade therapy is the development of combination therapies. As this approach has garnered worldwide interest, here, we have summarized the recent trends in the development of PD-1 blockade-based combination therapies and the ongoing clinical trials. These include combinations with checkpoint inhibitors, radiation therapy, chemotherapy and several other existing cancer treatments. Importantly, FDA has approved PD-1 blockade agent to be used in combination with either CTLA-4 blockade or chemotherapy. Responsiveness to the PD-1 blockade therapy is affected by tumour and immune system-related factors. The role of the immune system, especially T cells, in determining the responsiveness has been poorly studied compared with those factors related to the tumour side. Energy metabolism has emerged as one of the important regulatory mechanisms for the function and differentiation of T cells. We have documented here the recent results regarding the augmentation of PD-1 blockade efficacy by augmenting mitochondrial energy metabolism of T cell.

Ubiquitination and regulation of AURKA identifies a hypoxia-independent E3 ligase activity of VHL.

The hypoxia-regulated tumor-suppressor von Hippel-Lindau (VHL) is an E3 ligase that recognizes its substrates as part of an oxygen-dependent prolyl hydroxylase (PHD) reaction, with hypoxia-inducible factor α (HIFα) being its most notable substrate. Here we report that VHL has an equally important function distinct from its hypoxia-regulated activity. We find that Aurora kinase A (AURKA) is a novel, hypoxia-independent target for VHL ubiquitination. In contrast to its hypoxia-regulated activity, VHL mono-, rather than poly-ubiquitinates AURKA, in a PHD-independent reaction targeting AURKA for degradation in quiescent cells, where degradation of AURKA is required to maintain the primary cilium. Tumor-associated variants of VHL differentiate between these two functions, as a pathogenic VHL mutant that retains intrinsic ability to ubiquitinate HIFα is unable to ubiquitinate AURKA. Together, these data identify VHL as an E3 ligase with important cellular functions under both normoxic and hypoxic conditions.

Targeting Alpha Toxin and ClfA with a Multimechanistic Monoclonal-Antibody-Based Approach for Prophylaxis of Serious Staphylococcus aureus Disease.

UNLABELLED: Staphylococcus aureus produces numerous virulence factors, each contributing different mechanisms to bacterial pathogenesis in a spectrum of diseases. Alpha toxin (AT), a cytolytic pore-forming toxin, plays a key role in skin and soft tissue infections and pneumonia, and a human anti-AT monoclonal antibody (MAb), MEDI4893*, has been shown to reduce disease severity in dermonecrosis and pneumonia infection models. However, interstrain diversity and the complex pathogenesis of S. aureus bloodstream infections suggests that MEDI4893* alone may not provide adequate protection against S. aureus sepsis. Clumping factor A (ClfA), a fibrinogen binding protein, is an important virulence factor facilitating S. aureus bloodstream infections. Herein, we report on the identification of a high-affinity anti-ClfA MAb, 11H10, that inhibits ClfA binding to fibrinogen, prevents bacterial agglutination in human plasma, and promotes opsonophagocytic bacterial killing (OPK). 11H10 prophylaxis reduced disease severity in a mouse bacteremia model and was dependent on Fc effector function and OPK. Additionally, prophylaxis with 11H10 in combination with MEDI4893* provided enhanced strain coverage in this model and increased survival compared to that obtained with the individual MAbs. The MAb combination also reduced disease severity in murine dermonecrosis and pneumonia models, with activity similar to that of MEDI4893* alone. These results indicate that an MAb combination targeting multiple virulence factors provides benefit over a single MAb neutralizing one virulence mechanism by providing improved efficacy, broader strain coverage, and protection against multiple infection pathologies. IMPORTANCE: Alternative strategies to broad-spectrum antibiotics are required to combat the antibiotic resistance epidemic. Previous attempts at active or passive immunization against Staphylococcus aureus targeting single antigens have failed in clinical trials despite positive preclinical data. To provide broad disease and isolate coverage, an effective immunization strategy likely must target multiple virulence mechanisms of the pathogen. Herein, we tested a multimechanistic MAb combination targeting alpha toxin (AT) and clumping factor A (ClfA) that neutralizes AT-mediated cytotoxicity, blocks fibrinogen binding by ClfA, prevents bacterial agglutination, targets the bacteria for opsonophagocytic killing, and provides broad isolate coverage in a lethal-bacteremia model. Although each MAb alone was effective in bacteremia against some individual isolates, the MAb combination provided improved protection against other isolates. These results illustrate the importance of targeting multiple virulence mechanisms and highlight the potential for an MAb combination targeting AT and ClfA to effectively prevent S. aureus disease.

Isolation, culture optimization and physico-chemical characterization of laccase enzyme from Pleurotus fossulatus.

Pleurotus fossulatus (Cooke) Sace is member of oyster mushroom can produced extracellular laccase (benzenediol: oxygen oxidoreductase; EC 1.10.3.2) in submerged fermentation. To analyze the optimum production for laccase P. fossulatus was cultured both in stationary and shaking condition in different media. Partial purification of laccase was done after 0-80% ammonium sulphate precipitation, followed by DEAE (Diethylaminoethyl) Sephadex (A-50) anion exchange chromatography. Potato-sucrose peptone (PSP) medium and Potato-dextrose (PD) medium showed highest laccase production in shaking and stationary conditions, respectively. Though the time required for optimum laccase production in stationary condition was much more than the shaking condition but the amount of laccase was about 2.75t greater in former condition. The laccase produced in stationary condition was more stable than the enzyme produced in shaking condition. The partially purified enzyme showed highest affinity towards o-dianisidine than guaiacol and ABTS (2,2'-Azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) as evidenced by their K(m). The physico-chemical properties of the laccase suggested the significance of this enzyme in industrial applications.

Fission barrier of superheavy nuclei and persistence of shell effects at high spin: cases of 254No and 220Th.

We report on the first measurement of the fission barrier height in a heavy shell-stabilized nucleus. The fission barrier height of 254No is measured to be Bf=6.0±0.5 MeV at spin 15ℏ and, by extrapolation, Bf=6.6±0.9 MeV at spin 0ℏ. This information is deduced from the measured distribution of entry points in the excitation energy versus spin plane. The same measurement is performed for 220Th and only a lower limit of the fission barrier height can be determined: Bf(I)>8 MeV. Comparisons with theoretical fission barriers test theories that predict properties of superheavy elements.

Dengue outbreak in an Indo-Myanmar boarder area: epidemiological aspects and risk factors.

During October 2007, a large outbreak of suspected dengue fever (DF) was reported in Moreh township, Manipur: the first widespread outbreak in Northeast India. A cross sectional study was carried out in Moreh. The information on outbreak was collected and then described in time, place and person characteristics to arrive at aetiological hypotheses. Two hundred and eighty two serum samples were collected. Ninety one samples were reported positive for acute infection with dengue virus. Co-circulation of all the four dengue virus serotypes (1-4) and concurrent infection of 2 & 3, 1 & 3, and 1 & 4 serotypes was found. Predominant clinical features of the patients were fever (100%), headache (39%), vomiting (9.8%) and joint pain (4.16%). Haemorrhagic manifestation was recorded in one patient who subsequently died. Entomological surveys revealed profuse breeding of Aedes mosquitoes in all the affected municipal wards with high HI (37.5-71.43%), CI (53.84-86.95%) and BI (80-208.33%). Presence of IgM antibody, co-circulation of all the serotypes and concurrent infection with more than one serotype in the same individual confirmed the outbreak due to dengue virus infection. Preventive and control measures undertaken following the epidemiological investigation helped in controlling the outbreak.

Genetic analyses of ribosomal loci of Anopheles minimus species from north east India.

Anopheles minimus is one of the major vectors for transmission of malaria disease in north eastern (NE) region of India. The minimus species complex of Minimus subgroup of Myzomyia series of anophelines were studied in malaria affected states--Assam and Arunachal Pradesh (AP) of NE India. Ribosomal DNA markers--second internal transcribed spacer (ITS2) and third domain (D3) of 28S gene were used to characterize An. minimus species. Sequence homogeneity was observed in D3 sequences of An.minimus specimens throughout both the states. However, a transversion in ITS2 sequence of single specimen collected from Assam-Meghalaya border areas illustrates possibility of intra population polymorphism in ITS2 sequence within the geographical region.

Fine-grained lower limit of entropic uncertainty in the presence of quantum memory.

The limitation on obtaining precise outcomes of measurements performed on two noncommuting observables of a particle as set by the uncertainty principle in its entropic form can be reduced in the presence of quantum memory. We derive a new entropic uncertainty relation based on fine graining, which leads to an ultimate limit on the precision achievable in measurements performed on two incompatible observables in the presence of quantum memory. We show that our derived uncertainty relation tightens the lower bound set by entropic uncertainty for members of the class of two-qubit states with maximally mixed marginals, while accounting for the recent experimental results using maximally entangled pure states and mixed Bell-diagonal states. An implication of our uncertainty relation on the security of quantum key generation protocols is pointed out.

Efficacy of isometric exercise full knee extension horizontally (FKEH)--a new and simple maneuver to predict early onset of hypertension.

Hypertension is recognized as one of the risk factors for cardiovascular mortality and morbidity. Early identification of persons at increased risk for developing hypertension is a priority, which help them, to live a healthy life by altering lifestyle. Persons having predisposing factors of hypertension (e.g., family history of hypertension) show blood pressure hyper-responsiveness to stress. Elevated blood pressure due to sympathetic stimulation prevailed longer time in susceptible persons. In previous studies some instruments (e.g., hand immersion in cold (4 degrees C) water or isometric exercise by handgrip dynamometer) were required to elicit sympathetic stimulation. In the present study a simple maneuver Full Knee Extension Horizontally (FKEH) has been introduced--a stressor that caused full isometric contraction of quadriceps femoris muscles of both sides. The test was conducted in normotensive, non-smoker males (n = 150) of age group 18-25 years. Among them some (n = 100) were from families having no history of familial hypertension and others (n = 50) were from the families with history of hypertension. The causal blood pressure and heart rate of the participants were recorded. Then the volunteers were requested to perform FKEH maneuver for one minute. Both blood pressure and heart rate were recorded immediately after and 3 minutes following FKEH. The data analyzed using t-test showed that, diastolic blood pressure didn't return and stabilized to pre-exercise level even after 3 minutes following FKEH in volunteers who were mostly from hypertensive family (P< 0.05) i.e., having predisposing factors of hypertension. This indicated those people are prone to early onset of hypertension as their Autonomic Nervous System (ANS) is not competent enough to stabilize their blood pressure to pre-exercise level. Hence, stress in the form of FKEH for one minute may be used as a bedside test to assess the competence of ANS and the proneness of developing early hypertension.

Gamma-ray emission probabilities in the decay of (177m)Lu.

γ-Ray emission probabilities from the decay of the long-lived (T(1/2)=160.44d) isomeric state in (177m)Lu were measured with planar (LEPS) and coaxial Ge detectors. The isomer γ-ray and ß(-)-decay branching intensities were also determined. Measurements were carried out at low absolute efficiencies in order to minimize coincidence summing losses. The results are compared with the previous measurements.

Identification of anti-alpha toxin monoclonal antibodies that reduce the severity of Staphylococcus aureus dermonecrosis and exhibit a correlation between affinity and potency.

Staphylococcus aureus alpha toxin (AT) is an important virulence determinant and may be a valid target for immunoprophylaxis against staphylococcal disease. Here we report the identification of potent inhibitory anti-AT monoclonal antibodies (MAbs) derived using B-cell hybridoma technology from VelocImmune mice engineered to produce IgG with a human variable domain. A small panel of inhibitory MAbs blocked AT-mediated lysis of rabbit red blood cells, A549 human lung epithelial cells, and THP-1 human monocytic cells, in a dose-dependent manner. Binding studies indicated that these MAbs recognize a similar epitope on AT and exhibit dissociation constants (K(D)) ranging from 0.50 to 15 nM. In an S. aureus dermonecrosis model, mice passively immunized with anti-AT inhibitory MAbs exhibited significant reductions of lesion size relative to mice treated with an irrelevant IgG control. Interestingly, there was a correlation between MAb affinity for a single epitope, the 50% inhibitory concentration (IC(50)) in the AT hemolytic assay, and lesion size reduction in the dermonecrosis model. A representative high-affinity MAb, 2A3.1, was demonstrated to significantly reduce lesion size following infection with three different clinical isolates (USA300, CC30, and CC5). Taken together, these results indicate that in vitro potency of anti-AT MAbs predicts in vivo potency in this model, supporting their continued preclinical evaluation as molecules for immunoprophylaxis against staphylococcal skin and soft tissue infections caused by diverse clinical isolates.