Fermentation kinetics including product and substrate inhibitions plus biomass death: a mathematical analysis

Fermentation is generally modelled by kinetic equations giving the time evolutions for biomass, substrate, and product concentrations. Although these equations can be solved analytically in simple cases if substrate/product inhibition and biomass death are included, they are typically solved numerically. We propose an analytical treatment of the kinetic equations --including cell death and an arbitrary number of inhibitions-- in which constant yield needs not be assumed. Equations are solved in phase space, i.e. the biomass concentration is written explicitly as a function of the substrate concentration.Comment: 4 pages, 4 figure

Detection of chromosome aberrations in the human interphase nucleus by visualization of specific target DNAs with radioactive and non-radioactive in situ hybridization techniques: diagnosis of trisomy 18 with probe L1.84

The localization of chromosome 18 in human interphase nuclei is demonstrated by use of radioactive and nonradioactive in situ hybridization techniques with a DNA clone designated L1.84. This clone represents a distinct subpopulation of the repetitive human alphoid DNA family, located in the centric region of chromosome 18. Under stringent hybridization conditions hybridization of L1.84 is restricted to chromosome 18 and reflects the number of these chromosomes present in the nuclei, namely, two in normal diploid human cells and three in nuclei from cells with trisomy 18. Under conditions of low stringency, cross-hybridization with other subpopulations of the alphoid DNA family occurs in the centromeric regions of the whole chromosome complement, and numerous hybridization sites are detected over interphase nuclei. Detection of chromosome-specific target DNAs by non-radioactive in situ hybridization with appropriate DNA probes cloned from individual chromosomal subregions presents a rapid means of identifying directly numerical or even structural chromosome aberrations in the interphase nucleus. Present limitations and future applications of interphase cytogenetics are discussed

Plankton community respiration and bacterial metabolism in a North Atlantic Shelf Sea during spring bloom development (April 2015)

Spring phytoplankton blooms are important events in Shelf Sea pelagic systems as the increase in carbon production results in increased food availability for higher trophic levels and the export of carbon to deeper waters and the sea-floor. It is usually accepted that the increase in phytoplankton abundance and production is followed by an increase in plankton respiration. However, this expectation is derived from field studies with a low temporal sampling resolution (5–15 days). In this study we have measured the time course of plankton abundance, gross primary production, plankton community respiration, respiration of the plankton size classes (> 0.8 μm and 0.2–0.8 μm) and bacterial production at ≤5 day intervals during April 2015 in order to examine the phasing of plankton autotrophic and heterotrophic processes. Euphotic depth-integrated plankton community respiration increased five-fold (from 22 ± 4 mmol O2m−2 d−1 on 4th April to 119 ± 4 mmol O2m−2 d−1 on 15th April) at the same time as gross primary production also increased five-fold, (from 114 ± 5 to 613 ± 28 mmol Cm−2 d−1). Bacterial production began to increase during the development of the bloom, but did not reach its maximum until 5 days after the peak in primary production and plankton respiration. The increase in plankton community respiration was driven by an increase in the respiration attributable to the> 0.8 μm size fraction of the plankton community (which would include phytoplankton, microzooplankton and particle attached bacteria). Euphotic depth-integrated respiration of the 0.2–0.8 μm size fraction (predominantly free living bacteria) decreased and then remained relatively constant (16 ± 3 – 11 ± 1 mmol O2m−2 d−1) between the first day of sampling (4th April) and the days following the peak in chlorophyll-a (20th and 25th April). Recent locally synthesized organic carbon was more than sufficient to fulfil the bacterial carbon requirement in the euphotic zone during this productive period. Changes in bacterial growth efficiencies (BGE, the ratio of bacterial production to bacterial carbon demand) were driven by changes in bacterial production rates increasing from<30 ± 14% on 4th April to 51 ± 11% on 25th of April. This study therefore shows a concurrent rather than a phased increase in primary production and community respiration attributable to cells>0.8 μm during the development of the spring bloom, followed 5 days later by a peak in bacterial production. In addition, the size fractionated respiration rates and high growth efficiencies suggest that free living bacteria are not the major producers of CO2 before, during and a few days after this shelf sea spring phytoplankton bloom

Pentraxins coordinate excitatory synapse maturation and circuit integration of parvalbumin interneurons

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Circuit computation requires precision in the timing, extent, and synchrony of principal cell (PC) firing that is largely enforced by parvalbumin-expressing, fast-spiking interneurons (PVFSIs). To reliably coordinate network activity, PVFSIs exhibit specialized synaptic and membrane properties that promote efficient afferent recruitment such as expression of high-conductance, rapidly gating, GluA4-containing AMPA receptors (AMPARs). We found that PVFSIs upregulate GluA4 during the second postnatal week coincident with increases in the AMPAR clustering proteins NPTX2 and NPTXR. Moreover, GluA4 is dramatically reduced in NPTX2(-/-)/NPTXR(-/-) mice with consequent reductions in PVFSI AMPAR function. Early postnatal NPTX2(-/-)/NPTXR(-/-) mice exhibit delayed circuit maturation with a prolonged critical period permissive for giant depolarizing potentials. Juvenile NPTX2(-/-)/NPTXR(-/-) mice display reduced feedforward inhibition yielding a circuit deficient in rhythmogenesis and prone to epileptiform discharges. Our findings demonstrate an essential role for NPTXs in controlling network dynamics highlighting potential therapeutic targets for disorders with inhibition/excitation imbalances such as schizophrenia.Work supported by a PRAT fellowship to M.S.W., an NICHD intramural award to C.J.M., NIDCD intramural research program funding to R.S.P., an NIMH intramural award to H.A.C., NIH grants (PAR-02-059, NS 039156) to P.F.W., and an NIH grant (EY022730) to M.T.

Canine respiratory coronavirus employs caveolin-1-mediated pathway for internalization to HRT-18G cells

Canine respiratory coronavirus (CRCoV), identified in 2003, is a member of the Coronaviridae family. The virus is a betacoronavirus and a close relative of human coronavirus OC43 and bovine coronavirus. Here, we examined entry of CRCoV into human rectal tumor cells (HRT-18G cell line) by analyzing co-localization of single virus particles with cellular markers in the presence or absence of chemical inhibitors of pathways potentially involved in virus entry. We also targeted these pathways using siRNA. The results show that the virus hijacks caveolin-dependent endocytosis to enter cells via endocytic internalization

Testing the cognitive-behavioural maintenance models across DSM-5 bulimic-type eating disorder diagnostic groups: A multi-centre study

The original cognitive-behavioural (CB) model of bulimia nervosa, which provided the basis for the widely used CB therapy, proposed that specific dysfunctional cognitions and behaviours maintain the disorder. However, amongst treatment completers, only 40–50 % have a full and lasting response. The enhanced CB model (CB-E), upon which the enhanced version of the CB treatment was based, extended the original approach by including four additional maintenance factors. This study evaluated and compared both CB models in a large clinical treatment seeking sample (N = 679), applying both DSM-IV and DSM-5 criteria for bulimic-type eating disorders. Application of the DSM-5 criteria reduced the number of cases of DSM-IV bulimic-type eating disorders not otherwise specified to 29.6 %. Structural equation modelling analysis indicated that (a) although both models provided a good fit to the data, the CB-E model accounted for a greater proportion of variance in eating-disordered behaviours than the original one, (b) interpersonal problems, clinical perfectionism and low self-esteem were indirectly associated with dietary restraint through over-evaluation of shape and weight, (c) interpersonal problems and mood intolerance were directly linked to binge eating, whereas restraint only indirectly affected binge eating through mood intolerance, suggesting that factors other than restraint may play a more critical role in the maintenance of binge eating. In terms of strength of the associations, differences across DSM-5 bulimic-type eating disorder diagnostic groups were not observed. The results are discussed with reference to theory and research, including neurobiological findings and recent hypotheses

Examining a staging model for anorexia nervosa: empirical exploration of a four stage model of severity.

Background: An illness staging model for anorexia nervosa (AN) has received increasing attention, but assessing the merits of this concept is dependent on empirically examining a model in clinical samples. Building on preliminary findings regarding the reliability and validity of the Clinician Administered Staging Instrument for Anorexia Nervosa (CASIAN), the current study explores operationalising CASIAN severity scores into stages and assesses their relationship with other clinical features. Method: In women with DSM-IV-R AN and sub-threshold AN (all met AN criteria using DSM 5), receiver operating curve (ROC) analysis (n = 67) assessed the relationship between the sensitivity and specificity of each stage of the CASIAN. Thereafter chi-square and post-hoc adjusted residual analysis provided a preliminary assessment of the validity of the stages comparing the relationship between stage and treatment intensity and AN sub-types, and explored movement between stages after six months (Time 3) in a larger cohort (n = 171). Results: The CASIAN significantly distinguished between milder stages of illness (Stage 1 and 2) versus more severe stages of illness (Stages 3 and 4), and approached statistical significance in distinguishing each of the four stages from one other. CASIAN Stages were significantly associated with treatment modality and primary diagnosis, and CASIAN Stage at Time 1 was significantly associated with Stage at 6 month follow-up. Conclusions: Provisional support is provided for a staging model in AN. Larger studies with longer follow-up of cases are now needed to replicate and extend these findings and evaluate the overall utility of staging as well as optimal staging models

Alu-Alu Recombination Underlying the First Large Genomic Deletion in GlcNAc-Phosphotransferase Alpha/Beta (GNPTAB) Gene in a MLII Alpha/Beta Patient

Mucolipidosis type II α/β is a severe, autosomal recessive lysosomal storage disorder, caused by a defect in the GNPTAB gene that codes for the α/β subunits of the GlcNAc-phosphotransferase. To date, over 100 different mutations have been identified in MLII α/β patients, but no large deletions have been reported. Here we present the first case of a large homozygous intragenic GNPTAB gene deletion (c.3435-386_3602 + 343del897) encompassing exon 19, identified in a ML II α/β patient. Long-range PCR and sequencing methodologies were used to refine the characterization of this rearrangement, leading to the identification of a 21 bp repetitive motif in introns 18 and 19. Further analysis revealed that both the 5' and 3' breakpoints were located within highly homologous Alu elements (Alu-Sz in intron 18 and Alu-Sq2, in intron 19), suggesting that this deletion has probably resulted from Alu-Alu unequal homologous recombination. RT-PCR methods were used to further evaluate the consequences of the alteration for the processing of the mutant pre mRNA GNPTAB, revealing the production of three abnormal transcripts: one without exon 19 (p.Lys1146_Trp1201del); another with an additional loss of exon 20 (p.Arg1145Serfs*2), and a third in which exon 19 was substituted by a pseudoexon inclusion consisting of a 62 bp fragment from intron 18 (p.Arg1145Serfs*16). Interestingly, this 62 bp fragment corresponds to the Alu-Sz element integrated in intron 18.This represents the first description of a large deletion identified in the GNPTAB gene and contributes to enrich the knowledge on the molecular mechanisms underlying causative mutations in ML II.This work was supported by FCT - project PIC/IC/83252/2007 (http://alfa.fct.mctes.pt/). Coutinho MF and Quental S received grants from the FCT (SFRH/BD/48103/2008; SFRH/BPD/64025/2009)