Miracle-dz/UniFAR-FTUs huggingface dataset:
Selection on phenotypic plasticity favors thermal canalization

Significance Organisms are increasingly challenged by increasing temperatures due to climate change. In insects, body temperatures are strongly affected by ambient temperatures, and insects are therefore expected to suffer increasingly from heat stress, potentially reducing survival and reproductive success leading to elevated extinction risks. We investigated how ambient temperature affected fitness in two insect species in the temperate zone. Male and female survivorship benefitted more from low temperatures than did reproductive success, which increased with higher temperatures, revealing a thermal conflict between fitness components. Male body temperature plasticity reduced survival, and natural and sexual selection operated on such thermal plasticity. Our results reveal the negative consequences of thermal plasticity and show that these insects have limited ability to buffer heat stress. Climate change affects organisms worldwide with profound ecological and evolutionary consequences, often increasing population extinction risk. Climatic factors can increase the strength, variability, or direction of natural selection on phenotypic traits, potentially driving adaptive evolution. Phenotypic plasticity in relation to temperature can allow organisms to maintain fitness in response to increasing temperatures, thereby “buying time” for subsequent genetic adaptation and promoting evolutionary rescue. Although many studies have shown that organisms respond plastically to increasing temperatures, it is unclear if such thermal plasticity is adaptive. Moreover, we know little about how natural and sexual selection operate on thermal reaction norms, reflecting such plasticity. Here, we investigate how natural and sexual selection shape phenotypic plasticity in two congeneric and phenotypically similar sympatric insect species. We show that the thermal optima for longevity and mating success differ, suggesting temperature-dependent trade-offs between survival and reproduction in both sexes. Males in these species have similar thermal reaction norm slopes but have diverged in baseline body temperature (intercepts), being higher for the more northern species. Natural selection favored reduced thermal reaction norm slopes at high ambient temperatures, suggesting that the current level of thermal plasticity is maladaptive in the context of anthropogenic climate change and that selection now promotes thermal canalization and robustness. Our results show that ectothermic animals also at high latitudes can suffer from overheating and challenge the common view of phenotypic plasticity as being beneficial in harsh and novel environments.
Social Support, Drug Use, and Employment Among Low-Income Women

This study examined social support and its association with employment, income, and drug use in a sample of 534 low-income women. Functional support was defined as the perceived quality of one's interactions with others. Structural support was defined as the number of individuals within five particular types of networks: social, employment, drug, close, and emergency. Over the two-year study period, significant increases were observed in hours worked, income from work, income from other sources, and total income. There was also a significant decrease in welfare income. Results suggest that the perceived quality of support received is an important factor in achieving positive employment outcomes.
Biologic therapies in type 1 diabetes: how far are they from us?

DOI: 10.3760/cma.j.issn.0366-6999.20132375 Diabetes Center, Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Key Laboratory of Diabetes Immunology, Ministry of Education, Central South University, Changsha, Hunan 410011, China (Deng C, Xiang YF and Zhou ZG) Correspondence to: ZHOU Zhi-guang, Diabetes Center, Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Key Laboratory of Diabetes Immunology, Ministry of Education, Central South University, Changsha, Hunan 410011, China (Tel: 86-73185292154. Fax: 86-731-85367220. Email: zhouzg@hotmail.com) This study was supported by grants from the National Natural Science Foundation of China (No. 81170725), Program for Changjiang Scholars and Innovative Research Team in University (No. IRT1195), and Independent Innovative Projects for Graduates in Central South University (No. 2013zzts329). Editorial
Comparison of von Willebrand factor antigen, von Willebrand factor‐cleaving protease and protein S in blood components used for treatment of thrombotic thrombocytopenic purpura

Summary. Replacement of normal levels of von Willebrand factor‐cleaving protease (VWF:CP, ADAMTS13) activity from infused plasma is important in plasma exchange (PEX) for the treatment of thrombotic thrombocytopenic purpura (TTP) patients. We have studied the VWF:CP activity, VWF multimer distribution, VWF:Ag, protein S (PS) activity and free PS antigen levels in fresh frozen plasma (FFP), cryosupernatant (CSP) and virally inactivated components treated with methylene blue/light (MB) or solvent detergent (SD) processes. VWF:CP activity was normal in all components tested and was retained following overnight storage at room temperature. CSP and SD plasma contained reduced levels of the highest molecular weight VWF multimers. Protein S activity was reduced below the normal range in SD plasma, but within the normal range for the other components tested. Virally inactivated SD‐ and MB‐treated plasma may be an effective alternative to FFP and CSP in PEX for TTP. Reduced PS activity in SD plasma may predispose to venous thromboembolism, especially if infused in large volumes.
Prolactin-Induced Expression of Intercellular Adhesion Molecule-1 and the Accumulation of Monocytes/Macrophages During Regression of the Rat Corpus Luteum1

Abstract Intercellular adhesion molecule-1 (ICAM-1) is thought to facilitate the recruitment and migration of monocytes/macrophages to sites of inflammation. Here we investigated whether the luteolytic effect of prolactin in the hypophysectomized rat is associated with the expression of ICAM-1. In addition, we examined the effect of exogenous testosterone (or its potential conversion to estradiol endogenously) on the corpus luteum to address recent speculation that ovarian steroids might augment luteal regression. Immature, 30-day-old rats were ovulated with eCG and hCG and then hypophysectomized; this resulted in a single cohort of persistent corpora lutea. The rats were assigned randomly into four treatment groups: vehicle treatment without or with testosterone (VEH-T4, VEH+T4) and prolactin treatment without or with testosterone (PRL−T4, PRL+T4). Corpora lutea of control rats exhibited minimal ICAM-1 staining and contained relatively few monocytes/macrophages. In contrast, corpora lutea of prolactin-treated rats exhibited prominent ICAM-1 staining and contained numerous monocytes/macrophages. Testosterone did not overtly affect ICAM-1 staining, numbers of monocytes/macrophages, or concentrations of plasma progestins (progesterone and 20α-dihydroprogesterone) in either VEH or prolactin treatment groups; notwithstanding, luteal weights increased significantly in response to testosterone in VEH+T4 rats compared to VEH-T4 rats and prolactin-treated rats. We conclude that ICAM-1 expression and monocyte/macrophage accumulation are associated with prolactin-induced luteal regression in the rat and that these aspects are not influenced by testosterone.
Carotid atherosclerosis and cardiovascular risk stratification: Role and cost‐effectiveness of echo‐Doppler examination in untreated essential hypertensives

Objective. To investigate the impact and cost‐effectiveness of carotid ultrasonographic examination on total risk stratification in low–medium risk hypertensive patients in relation to age (<50 and ⩾50 years) and gender. Methods. Five hundred and eighty untreated hypertensives classified at low–medium risk, after the routine work‐up recommended by the 2003 ESH/ESC guidelines, were included in the study and total risk was reassessed by adding the results of carotid ultrasonography. Results. According to the stratification based on routine work‐up 16.3% of the whole population was considered at low added risk and 83.7% at medium added risk. Carotid subclinical damage was found in 158 patients (27.0%), who were then reclassified in the high‐risk stratum. Prevalence rates of patients reclassified in the high‐risk stratum as a consequence of carotid damage were as follows: 12.6% in men <50 years, 14.1% in women <50 years, 53.0% in men ⩾50 years and 40.1% in women ⩾50 years. The cost per detected case of carotid atherosclerosis was €473 in patients <50 years and €133 in those ⩾50 years. Conclusions. Our results show that: (i) the use of carotid ultrasonography allows a much more accurate identification of high‐risk individuals; (ii) its impact and cost‐effectiveness on the risk stratification process differs markedly according to the age and gender; (iii) the selective use of this procedure in subjects at high risk of target organ damage may substantially improve the cost of primary prevention.
Inversions produced during V(D)J rearrangement at IgH, the immunoglobulin heavy-chain locus

Diversity in immunoglobulin antigen receptors is generated in part by V(D)J recombination. In this process, different combinations of gene elements are joined in various configurations. Products of V(D)J recombination are coding joints, signal joints, and hybrid junctions, which are generated by deletion or inversion. To determine their role in the generation of diversity, we have examined two sorts of recombination products, coding joints and hybrid junctions, that have formed by inversion at the mouse immunoglobulin heavy-chain locus. We developed a PCR assay for quantification and characterization of inverted rearrangements of DH and JH gene elements. In primary cells from adult mice, inverted DJH rearrangements are detectable but they are rare. There were approximately 1,100 to 2,200 inverted DJH coding joints and inverted DJH hybrid junctions in the marrow of one adult mouse femur. On day 16 of gestation, inverted DJH rearrangements are more abundant. There are approximately 20,000 inverted DJH coding joints and inverted DJH hybrid junctions per day 16 fetal liver. In fetal liver cells, the number of inverted DJH rearrangements remains relatively constant from day 14 to day 16 of gestation. Inverted DJH rearrangements to JH4, the most 3' JH element, are more frequently detected than inverted DJH rearrangements to other JH elements. We compare the frequencies of inverted DJH rearrangements to previously determined frequencies of uninverted DJH rearrangements (DJH rearrangements formed by deletion). We suggest that inverted DJH rearrangements are influenced by V(D)J recombination mechanistic constraints and cellular selection.
The C-terminal Repeat Domain of Spt5 Plays an Important Role in Suppression of Rad26-independent Transcription Coupled Repair*

In eukaryotic cells, transcription coupled nucleotide excision repair (TCR) is believed to be initiated by RNA polymerase II (Pol II) stalled at a lesion in the transcribed strand of a gene. Rad26, the yeast homolog of the human Cockayne syndrome group B (CSB) protein, plays an important role in TCR. Spt4, a transcription elongation factor that forms a complex with Spt5, has been shown to suppress TCR in rad26Δ cells. Here we present evidence that Spt4 indirectly suppresses Rad26-independent TCR by protecting Spt5 from degradation and stabilizing the interaction of Spt5 with Pol II. We further found that the C-terminal repeat (CTR) domain of Spt5, which is dispensable for cell viability and is not involved in interactions with Spt4 and Pol II, plays an important role in the suppression. The Spt5 CTR is phosphorylated by the Bur kinase. Inactivation of the Bur kinase partially alleviates TCR in rad26Δ cells. We propose that the Spt5 CTR suppresses Rad26-independent TCR by serving as a platform for assembly of a multiple protein suppressor complex that is associated with Pol II. Phosphorylation of the Spt5 CTR by the Bur kinase may facilitate the assembly of the suppressor complex.
Plasma fibrinogen, haemostatic factors and prediction of peripheral arterial disease in the Edinburgh Artery Study

&NA; The role of fibrinogen and other haemostatic factors in prediction of peripheral arterial disease (PAD) has not been established. We examined the associations of plasma fibrinogen, von Willebrand Factor (vWF), tissue plasminogen activator (t‐PA) antigen, fibrin D‐dimer, and factor VII with the development and clinical progression of PAD. In the Edinburgh Artery Study, 1592 men and women, aged between 55 and 74 years, were followed prospectively over 5 years to detect the onset of PAD, and the deterioration of established PAD. At baseline, 418 individuals had evidence of PAD and 60 (14.4%) subsequently deteriorated. 1080 subjects had no baseline disease, but 59 (5.5%) developed PAD during follow‐up. Median levels of fibrinogen and vWF were higher in the group developing disease compared with the group which did not (2.78 g/l versus 2.57 g/l, P ≤ 0.01; 116 IU/dl versus 104 IU/dl, P ≤ 0.05; respectively). After adjusting for age and sex, fibrinogen (P ≤ 0.01) and vWF (P ≤ 0.05) were significantly associated with the risk of developing PAD. The association between fibrinogen and development of disease remained after adjusting for cardiovascular risk factors and baseline ischaemic heart disease (relative risk, 1.35, 95% confidence interval, 1.05, 1.73; P ≤ 0.05). None of the haemostatic factors were significantly associated with progression of PAD. In conclusion, plasma fibrinogen levels are related to the future onset of PAD, providing further evidence of a possible role of elevated fibrinogen in the development of atherosclerotic disease.
Thrombopoietin-Mediated Sustained Activation of Extracellular Signal-Regulated Kinase in UT7-Mpl Cells Requires Both Ras–Raf-1- and Rap1–B-Raf-Dependent Pathways

ABSTRACT Thrombopoietin (TPO) regulates growth and differentiation of megakaryocytes. We previously showed that extracellular signal-regulated kinases (ERKs) are required for TPO-mediated full megakaryocytic maturation in both normal progenitors and a megakaryoblastic cell line (UT7) expressing the TPO receptor (Mpl). In these cells, intensity and duration of TPO-induced ERK signal are controlled by several regions of the cytoplasmic domain of Mpl. In this study, we explored the signaling pathways involved in this control. We show that the small GTPases Ras and Rap1 contribute together to TPO-induced ERK activation in UT7-Mpl cells and that they do so by activating different Raf kinases as downstream effectors: a Ras–Raf-1 pathway is required to initiate ERK activation while Rap1 sustains this signal through B-Raf. Indeed, (i) in cells expressing wild-type or mutant Mpl, TPO-induced Ras and Rap1 activation correlates with early and sustained phases of ERK signal, respectively; (ii) interfering mutants of Ras and Rap1 both inhibit ERK kinase activity and ERK-dependent Elk1 transcriptional activation in response to TPO; (iii) the kinetics of activation of Raf-1 and B-Raf by TPO follow those of Ras and Rap1, respectively; (iv) RasV12-mediated Elk1 activation was modulated by the wild type or interfering mutants of Raf-1 but not those of B-Raf; (v) Elk1 activation mediated by a constitutively active mutant of Rap1 (Rap1V12) is potentiated by B-Raf and inhibited by an interfering mutant of this kinase. UT7-Mpl cells represent the second cellular model in which Ras and Rap1 act in concert to modulate the duration of ERK signal in response to a growth factor and thereby the differentiation program. This is also, to our knowledge, the first evidence suggesting that Rap1 may play an active role in megakaryocytic maturation.
Identification of active users in synchronous CDMA multiuser detection

The level of multiple access interference (MAI) in code division multiple access (CDMA) communication systems is a time-varying parameter related to the number of active users. Almost all existing multiuser detection schemes were designed based on a priori information of the active users. In many situations, however, the multiuser receiver does not know the number of active users, and the receiver designed for the detection of all users may lead to poor performance. To develop a more efficient detection scheme in practical applications, we propose a two-stage detection structure consisting of preprocessing (identification) and postprocessing (detection). In the preprocessing, we apply the subspace concept and a method based on the multiple signal classification (MUSIC) algorithm to identify the active users while requiring only a priori knowledge of all of the users' signature sequences. The proposed preprocessor is shown to be asymptotically near-far resistant, and to have the ability to identify the active users in a simple and reliable way. While in the detection process, as we efficiently use the active users' information in every observation interval, the performance is clearly improved compared to the conventional structure without identification. Moreover, the effect of imperfect identification on the decorrelating detector is also extensively analyzed. Though the decorrelating detector's inherent near-far resistant characteristic is impaired by imperfect identification, the proposed structure still outperforms the conventional structure in the general near-far environment.
Which sexually active female students get themselves tested for Chlamydia trachomatis? A cohort study

Using data from the Prevention of Pelvic Infection (POPI) chlamydia screening trial, we compared the characteristics of female students who did or did not get tested for chlamydia outside the trial during 12 months’ follow-up. Of the 2529 women in the trial, we excluded 68 chlamydia positives in the intervention group who were referred for treatment at baseline. Of the remaining 2461 women, 1980 (80%) answered the question about testing during follow-up on their 12 months’ questionnaire and were included in the cohort. Of 1980 respondents, 529 (27%) reported having an independent chlamydia test, including 30 (48%) of 63 women with undiagnosed chlamydia at baseline. Predictors of testing included having undiagnosed chlamydia at baseline (adjusted odds ratio 2.44; 95% confidence interval 1.39–4.28), ≥2 sexual partners in the year prior to baseline (OR 1.99; 95% CI 1.60–2.48), history of sexually transmitted infection (1.63: 1.20–2.22); symptoms of pelvic discomfort, dyspareunia, abnormal vaginal discharge or inter-menstrual bleeding (1.38; 1.09–1.73); and black ethnicity (1.37, 1.06–1.76). Although more women with risk factors got tested, half of women with undiagnosed chlamydia did not get tested. To optimise detection of chlamydia, testing should be offered routinely.
Induction of Experimental Autoimmune Encephalomyelitis in IL-12 Receptor-β2-Deficient Mice: IL-12 Responsiveness Is Not Required in the Pathogenesis of Inflammatory Demyelination in the Central Nervous System1

IL-12 is thought to be involved in the susceptibility to experimental autoimmune encephalomyelitis (EAE), a Th1 cell-mediated autoimmune disorder of the CNS. IL-12 signals through a heterodimeric receptor (IL-12Rβ1/IL-12Rβ2), whose β2-chain is up-regulated on activated, autoreactive Th1 cells. Contrary to the expectation that the absence of IL-12Rβ2 would protect from EAE, we found that IL-12Rβ2-deficient mice developed earlier and more severe disease, with extensive demyelination and CNS inflammation. The inflammatory cells were mainly comprised of CD4+ T cells, monocyte/macrophages, and dendritic cells. Compared to wild-type mice, IL-12Rβ2-deficient mice exhibited significantly increased autoantigen-induced proliferative response and increased production of TNF-α, GM-CSF, IL-17, IL-18/IL-18Rα, and NO. In addition, we found significantly increased levels of IL-23p19 mRNA expression in spleen cells from immunized IL-12Rβ2−/− mice compared with wild-type mice. These findings indicate that IL-12 responsiveness is not required in the pathogenesis of inflammatory demyelination in the CNS, and that, in the absence of IL-12Rβ2, increased IL-23 and other inflammatory molecules may be responsible for increased severity of EAE.
Immunolocalization of collagenase in periodontal disease.

Immunoreactive collagenase was detected in four of eight specimens of diseased gingival tissue when sampled prior to treatment. Specimens taken From patients who had previously received initial therapy and whose tissues showed no clinical signs of inflammation, showed insignificant immunoreactive collagenase. All specimens were frozen within minutes of surgery. The enzyme was associated with connective tissue adjacent to the pocket epithelium and at the advancing front of the lesion. No enzyme was observed in association with intact gingival epithelium, Immunoreactive enzyme was frequently associated with inflammatory cells but the precise cellular origin of collagenase remains uncertain. These findings demonstrate the presence of tissue collagenase at sites of active collagen resorption thereby suggesting a degradative role for this enzyme in periodontal disease.
Relationship between the number of positive fecal occult blood tests and the diagnostic yield of colonoscopy.

BACKGROUND In 2007, Ontario launched a colon cancer screening program for average-risk individuals based on biennial fecal occult blood tests (FOBTs) on three fecal samples, followed by colonoscopy for individuals who tested positive. OBJECTIVE To determine whether >1 positive screening FOBT was predictive of finding advanced neoplasia at colonoscopy. METHODS A retrospective chart review of outpatient colonoscopic procedures performed at Hotel Dieu Hospital (Kingston, Ontario) in the first two years of the colon cancer screening program was conducted, focusing on endoscopic and pathological findings. RESULTS Of 5556 individuals undergoing colonoscopy, 346 were referred for positive FOBT. Overall, 41 (11.8%) patients with a positive FOBT had colon cancer. In 16 (4.6%) cases, the number of positive FOBTs was not reported. For the 330 individuals in whom the number of positive tests was specified, 198, 71 and 61 cases had one, two and three positive results, respectively. Cancer was found at colonoscopy in 11 (5.6%), 11 (15.5%) and 18 (29.5%) of individuals with one, two and three positive FOBT results, respectively (OR 3.0 [95% CI 1.2 to 7.3] and 6.5 [95% CI 2.8 to 15.0] for two or three positive FOBTs compared with one; P=0.015 and P<0.001, respectively). High-risk adenomas (>1 cm in diameter, villous component and⁄or high-grade dysplasia) were found in 41 (20.8%), 29 (42.0%) and 25 (41.0%) individuals with one, two and three positive FOBTs, respectively (OR 2.8 [95% CI 1.5 to 5.0] and 2.4 [95% CI 1.3 to 4.5] for two or three positive FOBTs compared with one; P=0.001 and P=0.006, respectively). CONCLUSIONS The diagnostic yield of colonoscopy varied directly with the number of positive FOBTs. This information may be useful in assigning scheduling priority for patients with positive FOBTs.