Structural and Functional Vocal Fold Epithelial Integrity Following Injury

Objectives/Hypothesis: An intact epithelium is an important part of vocal fold defense. Damage to the epithelium can compromise vocal fold homeostasis and protection of the host tissue from viral and bacterial invasion. Elucidating the effects of damage on epithelial architectural and barrier integrity provides insight into the role of epithelium in protecting vocal folds. Using an animal model, we evaluated the time course of structural and functional epithelial restoration following injury. Study Design: Prospective, controlled animal study. Methods: Forty rats underwent surgery to remove vocal fold mucosa unilaterally. Larynges were harvested at five time intervals between 3 to 90 days postinjury and were prepared for histological and permeability analyses. Results: Rapid restoration of structural integrity was demonstrated by return of a multilayerd epithelium, intercellular junctions, and basement membrane at 5 days postinjury. Atypical epithelial permeability was observed up to 5 weeks postinjury. Conclusion: Restoration of epithelial barrier integrity lags epithelial structural restoration. Consequently, epithelial regeneration cannot be equated with return of functional barrier integrity. Rather, ongoing leakiness of regenerated epithelium indicates that vocal folds remain at risk for damage, pathogen invasion, and remodeling postinjury

Transmission of bacterial infections to healthcare workers during intubation and respiratory care of patients with severe pneumonia

Exposure of healthcare workers to patients with rapidly fatal infections invariably raises concerns regarding the risk of occupational acquisition. We describe acquisition of Streptococcus pyogenes by 2 nurses from a patient with fatal pneumonia and review previously reported cases of transmission of bacterial pathogens from patients with pneumonia to healthcare workers

FKF1 conveys timing information for CONSTANS stabilization in photoperiodic flowering

Plants use day-length information to coordinate flowering time with the appropriate season to maximize reproduction. In Arabidopsis, the long-day specific expression of CONSTANS (CO) protein is crucial for flowering induction. Although light signaling regulates CO protein stability, the mechanism by which CO is stabilized in the long-day afternoon has remained elusive. Here we demonstrate that FLAVIN-BINDING, KELCH REPEAT, F-BOX 1 (FKF1) protein stabilizes CO protein in the afternoon in long days. FKF1 interacts with CO through its LOV domain, and blue light enhances this interaction. In addition, FKF1 simultaneously removes CYCLING DOF FACTOR 1 (CDF1) that represses CO and FLOWERING LOCUS T (FT) transcription. Together with CO transcriptional regulation, FKF1 protein controls robust FT mRNA induction through multiple feedforward mechanisms that accurately control flowering timing

Composição morfológica e bromatológica de pastagens de Pennisetum pirpureum submetidas a diferentes intervalos entre pastejos.

As composições bromatológica e morfológica são duas características qualitativas das plantas forrageiras de grande importância para o desempenho de bovinos em pastejo. Desse modo, o objetivo do ensaio experimental foi avaliar os efeitos de dois diferentes intervalos entre pastejos sobre a composição bromatológica e morfológica de pastagens de capim Elefante, pastejada por vacas lactantes. Os tratamentos testados foram: intervalo entre pastejos variável, determinado pela entrada dos animais na área a ser pastejada, quando o dossel atingisse 95% de interceptação de luz e intervalo entre pastejos fixo em 27 dias. O delineamento experimental foi o inteiramente casualizado com medidas repetidas no tempo (4 sub-periodos). Foram observados maiores (P<0,05) teores de extrato etéreo, fibra em detergente neutro e fibra em detergente ácido para o intervalo entre pastejos fixo em 27 dias. O intervalo entre pastejos variável proporcionou maior (P<0,05) teor de matéria mineral na forragem. Não foram observados efeitos dos tratamentos sobre os teores de matéria seca, proteína bruta e lignina. Houve maior massa de material senescido (P<0,05) e tendência (P~0,08) de maior massa de colmos para o intervalo entre pastejo fixo de 27 dias no pré e pós-pastejo. Houve também tendência (P=O,10) de maior massa de folhas para o intervalo entre pastejo variável no resíduo pós-pastejo. O intervalo entre pastejo variável melhorou os aspectos bromatológicos e morfológicos do capim Elefante

Características produtivas e qualitativas de pastagens de Pennisetum purpureum submetidas a diferentes intervalos entre pastejos.

O intervalo entre pastejos pode exercer forte influência nos aspectos produtivos e qualitativos das plantas forrageiras tropicais, com reflexos na produção dos animais mantidos em pastagens. Assim, o objetivo do ensaio experimental foi comparar os efeitos de dois diferentes intervalos entre pastejos sobre algumas caracteristicas produtivas e qualitativas do dossel de capim Elefante pastejado por vacas em lactação. Os tratamentos foram: intervalo entre pastejos variável, determinado pela entrada dos animais na área a ser pastejada, quando o dossel atingisse 95% de interceptação de luz e intervalo entre pastejos fixados em 27 dias. O delineamento experimental foi o inteiramente casualizado com medidas repetidas no tempo. A frequência de desfolha, a altura do dossel no pré e pós-pastejo,. a interceptação de luz pelo dossel e o índice de área foliar, foram maiores (PO,O5) dos tratamentos sobre a massa de forragem em pré e pós-pastejo. O intervalo entre pastejos fixado em 27 dias, durante a época das águas, proporcionou forragem de pior qualidade

Deletion of CDKAL1 Affects Mitochondrial ATP Generation and First-Phase Insulin Exocytosis

A variant of the CDKAL1 gene was reported to be associated with type 2 diabetes and reduced insulin release in humans; however, the role of CDKAL1 in β cells is largely unknown. Therefore, to determine the role of CDKAL1 in insulin release from β cells, we studied insulin release profiles in CDKAL1 gene knockout (CDKAL1 KO) mice.Total internal reflection fluorescence imaging of CDKAL1 KO β cells showed that the number of fusion events during first-phase insulin release was reduced. However, there was no significant difference in the number of fusion events during second-phase release or high K(+)-induced release between WT and KO cells. CDKAL1 deletion resulted in a delayed and slow increase in cytosolic free Ca(2+) concentration during high glucose stimulation. Patch-clamp experiments revealed that the responsiveness of ATP-sensitive K(+) (K(ATP)) channels to glucose was blunted in KO cells. In addition, glucose-induced ATP generation was impaired. Although CDKAL1 is homologous to cyclin-dependent kinase 5 (CDK5) regulatory subunit-associated protein 1, there was no difference in the kinase activity of CDK5 between WT and CDKAL1 KO islets.We provide the first report describing the function of CDKAL1 in β cells. Our results indicate that CDKAL1 controls first-phase insulin exocytosis in β cells by facilitating ATP generation, K(ATP) channel responsiveness and the subsequent activity of Ca(2+) channels through pathways other than CDK5-mediated regulation

Consanguinity decreases risk of breast cancer – cervical cancer unaffected

Marriages between third-degree and more distant relatives are common in many parts of the world. Offspring of consanguineous parents have increased morbidity and mortality related to recessive gene disorders. In a population with a high frequency of consanguinity, we examined the frequency of breast cancer (related in part to tumour genes) and cervical cancers (related to virus infection) among offspring of consanguineous and non-consanguineous parents. Study was done prospectively in the United Arab Emirates. Selected were married female citizens, ages 40–65, who attended 12 primary health care clinics for whatever reason. In a face-to-face interview, subjects were asked: (a) about consanguineous marriages in family; (b) if they have or have had breast or cervical cancer; (c) about family history of cancer, cancer screening and other parameters. Tumour diagnosis was confirmed by review of medical records. Of 1750 women invited into study, 1445 (79%) could be used in analysis. Among 579 (40%) women of consanguineous and 866 (60%) of non-consanguineous parents there were 24 and 54 with breast cancer, respectively (RR = 0.66, CI 0.42 – 1.06). In the 40 to 50 age group, breast cancer reported 13 of 446 women of consanguineous and 37 of 633 of non-consanguineous parents (RR = 0.50, Cl 0.27 – 0.93). Cervical cancer had 15 women in consanguineous and 32 in non-consanguineous group (RR = 0.70, Cl 0.38 – 1.28). Number of families with history of breast cancer in consanguineous and non-consanguineous group was 21 and 23, respectively (P = 0.29). The cancer screening rates and other variable values had fairly balanced distribution between the 2 groups. Having consanguineous parents decreases the risk of breast cancer especially in younger women, risk of cervical cancer being unaffected. © 2001 Cancer Research Campaign http://www.bjcancer.co

Transplantation of canine olfactory ensheathing cells producing chondroitinase ABC promotes chondroitin sulphate proteoglycan digestion and axonal sprouting following spinal cord injury

Olfactory ensheathing cell (OEC) transplantation is a promising strategy for treating spinal cord injury (SCI), as has been demonstrated in experimental SCI models and naturally occurring SCI in dogs. However, the presence of chondroitin sulphate proteoglycans within the extracellular matrix of the glial scar can inhibit efficient axonal repair and limit the therapeutic potential of OECs. Here we have used lentiviral vectors to genetically modify canine OECs to continuously deliver mammalian chondroitinase ABC at the lesion site in order to degrade the inhibitory chondroitin sulphate proteoglycans in a rodent model of spinal cord injury. We demonstrate that these chondroitinase producing canine OECs survived at 4 weeks following transplantation into the spinal cord lesion and effectively digested chondroitin sulphate proteoglycans at the site of injury. There was evidence of sprouting within the corticospinal tract rostral to the lesion and an increase in the number of corticospinal axons caudal to the lesion, suggestive of axonal regeneration. Our results indicate that delivery of the chondroitinase enzyme can be achieved with the genetically modified OECs to increase axon growth following SCI. The combination of these two promising approaches is a potential strategy for promoting neural regeneration following SCI in veterinary practice and human patients