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1.
Science ; 378(6621): eabg3679, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36395225

RESUMO

The Hippo signaling pathway is widely considered a master regulator of organ growth because of the prominent overgrowth phenotypes caused by experimental manipulation of its activity. Contrary to this model, we show here that removing Hippo transcriptional output did not impair the ability of the mouse liver and Drosophila eyes to grow to their normal size. Moreover, the transcriptional activity of the Hippo pathway effectors Yap/Taz/Yki did not correlate with cell proliferation, and hyperactivation of these effectors induced gene expression programs that did not recapitulate normal development. Concordantly, a functional screen in Drosophila identified several Hippo pathway target genes that were required for ectopic overgrowth but not normal growth. Thus, Hippo signaling does not instruct normal growth, and the Hippo-induced overgrowth phenotypes are caused by the activation of abnormal genetic programs.


Assuntos
Drosophila melanogaster , Olho , Regulação da Expressão Gênica no Desenvolvimento , Via de Sinalização Hippo , Fígado , Transcrição Gênica , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional , Proteínas de Sinalização YAP , Animais , Camundongos , Drosophila melanogaster/embriologia , Drosophila melanogaster/genética , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Olho/embriologia , Via de Sinalização Hippo/genética , Fígado/embriologia , Tamanho do Órgão , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Transativadores/genética , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional/metabolismo , Proteínas de Sinalização YAP/metabolismo
2.
Leukemia ; 32(4): 941-951, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29151585

RESUMO

T-cell acute lymphoblastic leukemia (T-ALL) is caused by the accumulation of multiple mutations combined with the ectopic expression of transcription factors in developing T cells. However, the molecular basis underlying cooperation between transcription factor expression and additional oncogenic mutations in driving T-ALL has been difficult to assess due to limited robust T-cell model systems. Here we utilize a new ex vivo pro-T-cell model to study oncogenic cooperation. Using a systems biological approach we first dissect the pro-T-cell signaling network driven by interleukin-7, stem cell factor and Notch1 and identify key downstream Akt, Stat, E2f and Myc genetic signaling networks. Next, this pro-T-cell system was used to demonstrate that ectopic expression of the TAL1 transcription factor and Pten deletion are bona-fide cooperating events resulting in an increased stem cell signature, upregulation of a specific E2f signaling network and metabolic reprogramming with higher influx of glucose carbons into the tricarboxylic acid cycle. This ex vivo pro-T-cell system thereby provides a powerful new model system to investigate how normal T-cell signaling networks are perturbed and/or hijacked by different oncogenic events found in T-ALL.


Assuntos
Oncogenes/genética , PTEN Fosfo-Hidrolase/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Deleção de Sequência/genética , Proteína 1 de Leucemia Linfocítica Aguda de Células T/genética , Linfócitos T/metabolismo , Animais , Carcinogênese/genética , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mutação/genética , PTEN Fosfo-Hidrolase/metabolismo , Transdução de Sinais/genética , Células-Tronco/metabolismo , Fatores de Transcrição/genética , Regulação para Cima/genética
3.
Biomed Res Int ; 2015: 943415, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25793213

RESUMO

The total whole-body exposure dose in indoor wireless networks is minimized. For the first time, indoor wireless networks are designed and simulated for a minimal exposure dose, where both uplink and downlink are considered. The impact of the minimization is numerically assessed for four scenarios: two WiFi configurations with different throughputs, a Universal Mobile Telecommunications System (UMTS) configuration for phone call traffic, and a Long-Term Evolution (LTE) configuration with a high data rate. Also, the influence of the uplink usage on the total absorbed dose is characterized. Downlink dose reductions of at least 75% are observed when adding more base stations with a lower transmit power. Total dose reductions decrease with increasing uplink usage for WiFi due to the lack of uplink power control but are maintained for LTE and UMTS. Uplink doses become dominant over downlink doses for usages of only a few seconds for WiFi. For UMTS and LTE, an almost continuous uplink usage is required to have a significant effect on the total dose, thanks to the power control mechanism.


Assuntos
Campos Eletromagnéticos/efeitos adversos , Exposição Ambiental/efeitos adversos , Ondas de Rádio/efeitos adversos , Adulto , Telefone Celular , Humanos , Masculino , Tecnologia sem Fio
5.
Reprod Domest Anim ; 47(3): 365-71, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21950479

RESUMO

Some anatomical characteristics of 507 Belgian Blue (BB) cattle, withers height (WH), heart girth (HG), the distance between the two tubera coxae (TcTc) and the distance between the two tubera ischiadica (TiTi), were compared with the internal pelvic measurements of width, height and area. Mean values were 58.9 ± 6.2 cm for TcTc, 14.6 ± 2.3 cm for TiTi, 15.2 ± 2.1 cm for pelvic width (PW), 18.8 ± 1.9 cm for pelvic height (PH) and 288.5 ± 60.9 cm(2) for pelvic area (PA). Cows that calved per vaginam had larger WH (p < 0.05), TcTc (p < 0.05) and TiTi (p < 0.001) and internal pelvic measurements [PH and PA (p < 0.001)] compared with those whose parturition was managed by caesarean section (CS): Correlations between internal pelvic measurements and TcTc were higher (r = 0.58-0.63) than TiTi (r = 0.22-0.28). Correlations between other external body measures such as HG and WH with the internal pelvic measurements were even higher for HG (r = 0.69-0.74) and for WH (r = 0.67-0.74). HG and WH, together with internal pelvic measures, may be added to estimated breeding values (EBV's) that should assist breeders in selecting cows that can calve per vaginam, thereby reducing the breed's dependence on elective CS for maintaining its unique characteristics.


Assuntos
Bovinos/anatomia & histologia , Bovinos/fisiologia , Ossos Pélvicos/anatomia & histologia , Pelve/anatomia & histologia , Envelhecimento , Animais , Bovinos/genética , Feminino
6.
Reprod Domest Anim ; 45(1): 160-7, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20175248

RESUMO

This article describes a study of the behaviour of double muscled Belgian Blue (BB) cows during the peri partum period to assess the differences in pain perception in cows calving per vaginam vs cows delivering by caesarean section (CS). In one herd, a total of 30 multiparous cows, of which 17 delivered by CS and 13 calved per vaginam, were closely observed at approximately 1 month before calving and at days 1, 3 and 14 after parturition. The main behavioural indicators of pain were alertness, transition in posture from standing to lying and vice versa, aggressive behaviour, vocalization, rumination quality, reaction on wound and vulva pressure and the percentage of visible eye-white. The main significant differences were lower overall activity and more transition in posture in animals that delivered by CS than in cows that calved naturally. Less time was spent on eating and ruminating in the CS group, their total resting time was longer and their total standing time was shorter. These significant differences were only observed on the first day after calving. Cows of the CS group reacted significantly more when pressure was put on the left flank on the first, third and fourteenth day after calving, whereas animals that calved per vaginam showed more reaction when pressure was put on the area around the vulva, but only on the first day. Based on the results of the present study, we can conclude that there are some significant short-term behavioural differences between BB cows that calve naturally and those that deliver by CS, but in general, the differences are subtle and of short duration.


Assuntos
Comportamento Animal/fisiologia , Bovinos/fisiologia , Cesárea/veterinária , Parto Obstétrico/veterinária , Medição da Dor/veterinária , Agressão/fisiologia , Animais , Ingestão de Alimentos , Feminino , Frequência Cardíaca , Hidrocortisona/sangue , Medição da Dor/métodos , Palpação/veterinária , Parto/fisiologia , Postura/fisiologia , Gravidez , Respiração , Rúmen/fisiologia , Vocalização Animal , Vulva
7.
Animal ; 4(5): 661-71, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-22444118

RESUMO

At calving, purebred animals of the Belgian Blue (BB) breed are compromised by the incompatibility in size and shape of the dam and her calf, resulting in a very high incidence of dystocia problems. To clarify which body parts of the calf are of decisive importance to allow natural delivery and to investigate both the mean value as well as the variation among these body sizes within this breed (variation being an important condition for selection), measurements of nine body parts (body weight at birth (BW), body length (BL), length of the head (LH), shoulder width (SW), hip width (HW), heart girth (HG), withers height (WH) and the circumference of the fetlock of both the front (CFF) and the hind leg (CFH)) were assessed in 147 newborn purebred BB calves on 17 farms. Simple and partial correlations were assessed and we examined whether environmental factors (gender of the calf, parity of the cow, type of calving, season of birth and time of measurement after birth) were significantly associated with these specific calf measurements. The mean BW was 49.2 ± 7.1 kg. The average BL was 56.4 ± 4.5 cm and the mean LH was 24.4 ± 2.3 cm. Measurements obtained for SW and HW were 22.4 ± 2.2 and 22.9 ± 2.1 cm, respectively, whereas the mean WH was 71.1 ± 4.7 cm. Measurements of circumferences revealed a CFF of 17.9 ± 1.1 cm, a CFH of 18.0 ± 1.0 cm and a mean HG of 78.0 ± 5.4 cm. Partial correlations of the BW with eight body measurements were significant (P < 0.01) and ranged between 0.17 and 0.85; 0.42 and 0.88; and 0.24 and 0.88 when corrected for gender, parity and type of calving, respectively. BL (P < 0.01) and the CFF and CFH (P < 0.001) are larger in bull calves than in heifer calves. Calves born through caesarean section had broader SW (P < 0.01) and HW (P < 0.01) when compared with calves born after natural calving (defined as born per vaginam without assistance or with slight traction). Sizes of calves born out of multiparous cows were generally larger than of calves born out of heifers (SW: P < 0.001; HW: P < 0.05). As SW and HW are the broadest points of a BB calf, they are both candidates for being the limiting measures for calving ease, but the difference between HW and SW for the total data set was not different from zero (P > 0.05). In contrast to male calves in which no significant difference (between HW and SW) could be found, female calves show the difference between HW and SW that was significantly different from zero (P < 0.001); thus, in female calves, the HW is the most limiting factor of the calf's body. The significant variation in some body measures between the calves and the strong correlation within these sizes raises the possibility of selection towards smaller calves aiming to limit the dystocia problem in the BB breed. Furthermore, on the basis of our results, we were able to build equations for the farmer to use at the moment of calving containing the LH, the CF and the calf's gender to estimate SW and HW, the limiting body parts of the calf to be born naturally. Together with the knowledge of the pelvic size of the dam, this information gives the obstetrician or the farmer a more accurate prediction of the probability of natural calving at parturition.

8.
Acta Chir Belg ; 109(6): 805-7, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-20184076

RESUMO

Tuberculosis of the thyroid gland is a very rare condition. A case of a 47-year-old female with a history of a euthyroid multi-nodular goitre is presented. The patient developed hoarseness due to right recurrent laryngeal nerve paralysis, confirmed with indirect laryngoscopy. On repeated ultrasound, volumetric progression of a dominant nodule in the inferior part of the right thyroid lobe was noticed. Fine needle aspiration was inconclusive. Diagnosis was ultimately based on histopathology of the surgical resection specimen.


Assuntos
Tuberculose Endócrina/diagnóstico , Antituberculosos/administração & dosagem , Biópsia por Agulha Fina , Comorbidade , Quimioterapia Combinada , Feminino , Bócio Nodular/epidemiologia , Humanos , Pessoa de Meia-Idade , Necrose , Doenças da Glândula Tireoide/microbiologia , Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/microbiologia , Tuberculose Endócrina/tratamento farmacológico , Tuberculose Endócrina/epidemiologia , Tuberculose Endócrina/patologia
9.
Chem Commun (Camb) ; (6): 710-1, 2004 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-15010793

RESUMO

The Co-Jacobsen complex, catalysing a hydrolytic kinetic resolution, was recycled in a semi-continuous operation using a laboratory prepared polymeric SRNF-membrane.

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