We find that claw marks are an important source of data on interactions between lions and giraffes. The lion Panthera leo is the most important http://www.selleckchem.com/products/DAPT-GSI-IX.html predator of the giraffe Giraffa camelopardalis (Berry, 1973; Dagg & Foster, 1982), yet the relationship between these species has been rarely studied. Lions may be the primary cause of death for giraffe calves (Dagg & Foster, 1982), which suffer an estimated 58–73% mortality in the first of year of life (Foster & Dagg, 1972; Leuthold & Leuthold, 1978; Pellew, 1983a). Although giraffe mortality drops off substantially after 1 year of age (Pellew, 1983a), lion predation remains a significant mortality factor for subadults and even

for adults (e.g. Hirst, 1969; Pienaar, 1969), which weigh 800–1200 kg (Owen-Smith, 1988) and reach heights of up to 4.5–5.5 m for females and males, respectively (Dagg & Foster, 1982; Pellew, 1983a). Direct observations of lion attacks on giraffes are rare. GSK3235025 concentration In a 3-year study of Serengeti lions, Schaller (1972) observed only 10 such attacks, none of which led to a kill. Consequently, little is known about the effects of lions on giraffe

mortality and behavior. What is known is largely anecdotal or inferred from short-term studies of giraffe demography or from carcass records. If the majority of attacks are occurring in conditions not conducive to direct observation, such as at night or in dense vegetation, then alternative sources of data will be required. In this paper, we examine lion predation on giraffes by applying a novel methodology that has been used primarily in marine biology: predation marks on live animals. Underwater predation is difficult to observe directly (Bertilsson-Friedman, 2006); thus, predation marks visible on surfacing animals are an important

source of data on predator–prey interactions. While predation marks cannot be used alone to estimate predation rates, they can be used to identify predatory species (e.g. Corkeron, Morris & Bryden, 1987; Cockcroft, Cliff & Ross, 1989), to elucidate attack behavior, to infer which age–sex classes of prey are better able to evade predation (e.g. Corkeron et al., 1987; Heithaus, learn more 2001) and to examine variation in predation risk over space and time (Heithaus, 2001; Bertilsson-Friedman, 2006). Similarly, the predation-mark method can increase the sample size of lion predation events on giraffes. Only a portion of lion attacks are fatal (Schaller, 1972; Funston, Mills & Biggs, 2001) and surviving prey may incur bite wounds or claw marks. Lion claw marks are distinctive and can be differentiated from marks inflicted by other predators (Figs 1 and 2). Claw marks are observed on giraffe carcasses (Schaller, 1972) and on live giraffes (Fig. 2). Interpretation of claw marks, however, requires caution. For example, an absence of claw marks in an age–sex class could indicate that all attacked individuals die, that no individuals are attacked or that too few individuals were sampled.

We find that claw marks are an important source of data on interactions between lions and giraffes. The lion Panthera leo is the most important TAM Receptor inhibitor predator of the giraffe Giraffa camelopardalis (Berry, 1973; Dagg & Foster, 1982), yet the relationship between these species has been rarely studied. Lions may be the primary cause of death for giraffe calves (Dagg & Foster, 1982), which suffer an estimated 58–73% mortality in the first of year of life (Foster & Dagg, 1972; Leuthold & Leuthold, 1978; Pellew, 1983a). Although giraffe mortality drops off substantially after 1 year of age (Pellew, 1983a), lion predation remains a significant mortality factor for subadults and even

for adults (e.g. Hirst, 1969; Pienaar, 1969), which weigh 800–1200 kg (Owen-Smith, 1988) and reach heights of up to 4.5–5.5 m for females and males, respectively (Dagg & Foster, 1982; Pellew, 1983a). Direct observations of lion attacks on giraffes are rare. click here In a 3-year study of Serengeti lions, Schaller (1972) observed only 10 such attacks, none of which led to a kill. Consequently, little is known about the effects of lions on giraffe

mortality and behavior. What is known is largely anecdotal or inferred from short-term studies of giraffe demography or from carcass records. If the majority of attacks are occurring in conditions not conducive to direct observation, such as at night or in dense vegetation, then alternative sources of data will be required. In this paper, we examine lion predation on giraffes by applying a novel methodology that has been used primarily in marine biology: predation marks on live animals. Underwater predation is difficult to observe directly (Bertilsson-Friedman, 2006); thus, predation marks visible on surfacing animals are an important

source of data on predator–prey interactions. While predation marks cannot be used alone to estimate predation rates, they can be used to identify predatory species (e.g. Corkeron, Morris & Bryden, 1987; Cockcroft, Cliff & Ross, 1989), to elucidate attack behavior, to infer which age–sex classes of prey are better able to evade predation (e.g. Corkeron et al., 1987; Heithaus, selleck chemicals 2001) and to examine variation in predation risk over space and time (Heithaus, 2001; Bertilsson-Friedman, 2006). Similarly, the predation-mark method can increase the sample size of lion predation events on giraffes. Only a portion of lion attacks are fatal (Schaller, 1972; Funston, Mills & Biggs, 2001) and surviving prey may incur bite wounds or claw marks. Lion claw marks are distinctive and can be differentiated from marks inflicted by other predators (Figs 1 and 2). Claw marks are observed on giraffe carcasses (Schaller, 1972) and on live giraffes (Fig. 2). Interpretation of claw marks, however, requires caution. For example, an absence of claw marks in an age–sex class could indicate that all attacked individuals die, that no individuals are attacked or that too few individuals were sampled.

Among the 34 patients who added FTC, 12 remained viremic on their last evaluable visit through week 144 (median duration of combination therapy = 59 weeks, range = 25-70 weeks); PCR amplification failed for 1; 5 showed no change in the pol/RT versus the last observation while they were on TDF monotherapy; 4 harbored distinct polymorphic site changes; and 2 developed

conserved site changes (rtL180L/M, rtA181T, and rtM204M/V and rtR192H; Table 3). Clonal analysis of the baseline sample for the patient harboring the rtL180L/M, rtA181T, and rtM204M/V mutations demonstrated the presence of these mutations as subpopulations on separate genomes (rtL180M and rtM204V at 3.7% and rtA181T at 7.4%). Phenotypic analysis of the viral pool containing the rtA181T mutation demonstrated that the virus was fully sensitive to inhibition by tenofovir BGB324 (Table 2). Clones containing the rtL180M and rtM204V mutations could not be obtained with the PCR primers used for phenotyping. For patient 026, the viral quasispecies pool, individual clones (n = 7), and an rtR192H site-directed mutant in the pCMVHBV backbone were all replication-defective in a cell

culture (Table 2). Thirteen patients experienced a confirmed virological breakthrough (10 and 3 in the TDF and ADV-TDF arms, respectively) during the 144 weeks of cumulative exposure to TDF monotherapy; nonadherence OTX015 cost to the study medication contributed to the majority of the virological breakthrough events (11/13, 85%), and all patients experiencing virological breakthrough remained phenotypically sensitive to inhibition by tenofovir (Table 4). Four patients experienced virological breakthrough while they were on combination FTC/TDF therapy (three and one in the TDF and ADV-TDF arms, respectively), virological breakthrough could be attributed to nonadherence in two of the click here four patients, and the virus obtained from these patients remained

phenotypically sensitive to inhibition by tenofovir and FTC (Table 4). We performed extensive genotypic and phenotypic analyses of 641 HBeAg+ and HBeAg− patients who received up to 144 weeks of TDF therapy. We identified six previously undescribed conserved site changes in the HBV pol/RT. These novel conserved site changes were located in areas of high variability within the HBV genome.19 None of these changes appeared to be related to tenofovir resistance, as demonstrated by the lack of phenotypic resistance to tenofovir in vitro, nor were they associated with a confirmed virological breakthrough. Phenotypic analysis was also performed for patients who experienced virological breakthrough because this can be a hallmark of resistance development. All of the viruses tested remained phenotypically sensitive to inhibition by tenofovir; this is consistent with the genotypic findings, which demonstrated no changes in the pol/RT among these patients.

Among the 34 patients who added FTC, 12 remained viremic on their last evaluable visit through week 144 (median duration of combination therapy = 59 weeks, range = 25-70 weeks); PCR amplification failed for 1; 5 showed no change in the pol/RT versus the last observation while they were on TDF monotherapy; 4 harbored distinct polymorphic site changes; and 2 developed

conserved site changes (rtL180L/M, rtA181T, and rtM204M/V and rtR192H; Table 3). Clonal analysis of the baseline sample for the patient harboring the rtL180L/M, rtA181T, and rtM204M/V mutations demonstrated the presence of these mutations as subpopulations on separate genomes (rtL180M and rtM204V at 3.7% and rtA181T at 7.4%). Phenotypic analysis of the viral pool containing the rtA181T mutation demonstrated that the virus was fully sensitive to inhibition by tenofovir www.selleckchem.com/products/Adriamycin.html (Table 2). Clones containing the rtL180M and rtM204V mutations could not be obtained with the PCR primers used for phenotyping. For patient 026, the viral quasispecies pool, individual clones (n = 7), and an rtR192H site-directed mutant in the pCMVHBV backbone were all replication-defective in a cell

culture (Table 2). Thirteen patients experienced a confirmed virological breakthrough (10 and 3 in the TDF and ADV-TDF arms, respectively) during the 144 weeks of cumulative exposure to TDF monotherapy; nonadherence Lenvatinib nmr to the study medication contributed to the majority of the virological breakthrough events (11/13, 85%), and all patients experiencing virological breakthrough remained phenotypically sensitive to inhibition by tenofovir (Table 4). Four patients experienced virological breakthrough while they were on combination FTC/TDF therapy (three and one in the TDF and ADV-TDF arms, respectively), virological breakthrough could be attributed to nonadherence in two of the learn more four patients, and the virus obtained from these patients remained

phenotypically sensitive to inhibition by tenofovir and FTC (Table 4). We performed extensive genotypic and phenotypic analyses of 641 HBeAg+ and HBeAg− patients who received up to 144 weeks of TDF therapy. We identified six previously undescribed conserved site changes in the HBV pol/RT. These novel conserved site changes were located in areas of high variability within the HBV genome.19 None of these changes appeared to be related to tenofovir resistance, as demonstrated by the lack of phenotypic resistance to tenofovir in vitro, nor were they associated with a confirmed virological breakthrough. Phenotypic analysis was also performed for patients who experienced virological breakthrough because this can be a hallmark of resistance development. All of the viruses tested remained phenotypically sensitive to inhibition by tenofovir; this is consistent with the genotypic findings, which demonstrated no changes in the pol/RT among these patients.

The present findings strengthen the notion that, in migraine with and without aura, the threshold for inducing inhibitory mechanisms of cortical excitability might be lower in the interictal period. This

could represent a protective mechanism counteracting cortical hyperresponsivity. Our results could be helpful to explain some conflicting neurophysiological findings in migraine and to get insight into the mechanisms underlying recurrence of the migraine learn more attacks. “
“Objective.— To determine whether controlled changes in barometric pressure activate rat spinal trigeminal neurons as a possible animal correlate of headaches. Background.— Changes in weather accompanied by changes in atmospheric pressure are suggested to trigger primary headaches. Mechanisms that increase neuronal activity in the rat spinal trigeminal nucleus may parallel

those that contribute to the generation of headaches. Methods.— Urethane anesthetized rats were placed in a climatic chamber, in which the air pressure could be selectively MLN0128 price manipulated. The parietal cranial dura mater and the spinal dura mater covering the medulla were exposed. Electrolyte-filled electrodes were introduced into the spinal trigeminal nucleus to record from neurons with receptive fields in facial areas and the cranial dura mater and/or the cornea and/or the temporal muscle. Arterial pressure and heart rate were monitored. The barometric pressure was lowered by 40 hPa during 8 minutes, kept at this level for 8 minutes and returned to the previous level. Results.— During lowering of the barometric pressure and the low pressure period a sample of neurons showed increased discharge rates. Group analysis revealed that it was the group of units with receptive fields click here in the cornea, but not in the dura mater or the temporal muscle, which was significantly activated when the animal was exposed

to low atmospheric pressure. Exposure of the cranial dura and opening of the cisterna magna did not prevent an increase in activity. In another sample of units the activity recorded after infusion of the nitric oxide donor sodium nitroprusside did not change under low pressure exposure. Arterial pressure and heart rate changed slightly during barometric pressure changes. Conclusions.— We conclude that distinct neurons in the trigeminal nucleus caudalis, particularly with preferential afferent input from the eye, respond to lowering of atmospheric pressure. Similar mechanisms may contribute to the generation of headaches during changes in weather. “
“Old headache medicines never die; they either fade away or come back in disguise. The disguise is often a new route of administration, which may work better, faster, more completely, with fewer adverse events, and/or have certain other advantages.

Gender and family history, can hinder the proper compliance with treatments, reducing its effectiveness. “
“Summary.  Physical activity has been considered as an important factor for bone density and as a factor facilitating prevention of osteoporosis. Bone density has been reported to be reduced in haemophilia. To examine the relation between different aspects of physical activity and bone mineral density (BMD) in patients with severe haemophilia on long-term prophylaxis. The study group consisted of 38 patients R428 chemical structure with severe haemophilia (mean age 30.5 years). All patients received long-term

prophylaxis to prevent bleeding. The bone density (BMD g cm−2) of the total body, lumbar spine, total hip, femoral neck and trochanter was measured by dual energy X-ray absorptiometry. Physical activity was assessed using the self-report Modifiable Activity Questionnaire, an instrument which collects information about leisure and occupational activities for the prior 12 months. There was only significant correlation between duration and intensity of vigorous physical activity and bone density

at lumber spine L1-L4; for duration (r = 0.429 and P = 0.020) and for intensity (r = 0.430 and P = 0.019); whereas no significant correlation between all aspects DAPT price of physical activity and bone density at any other measured sites. With adequate long-term prophylaxis, adult patients with haemophilia are maintaining bone mass, whereas the level of physical activity in terms of intensity and duration play a minor role.

These results may support the proposition that the responsiveness to mechanical strain is probably more important for bone mass development in children and during adolescence than in adults and underscores the importance of early onset prophylaxis. “
“This chapter contains sections titled: Clinical context Classification between high and low responders Products available Management of bleeding situations Conclusion References “
“Summary.  Recurrent musculoskeletal selleck screening library haemorrhages in people with haemophilia (PWH) lead to restrictions in the locomotor system and consequently in physical performance. Patients’ perceptions of their health status have gained an important role in the last few years. The assessment of subjective physical performance in PWH is a new approach. This study aimed to compare the subjective physical performance of PWH with healthy controls and to correlate the results with objective data. Subjective physical performance was assessed via the new questionnaire HEP-Test-Q, which consists of 25 items pertaining to four subscales ‘mobility’, ‘strength & coordination’, ‘endurance’ and ‘body perception’. HEP-Test-Q subscales were compared with objective data in terms of range of motion, one-leg-stand and 12-minute walk test. Forty-eight patients (44 ± 11 years) with haemophilia A (43 severe, three moderate) or B (two severe) and 43 controls without haemophilia (42 ± 11 years) were enrolled.

Abortives: peppermint oil, lavender, passion flower, rosemary, chamomile, rose hips, valerian, boswellia, rizatriptan, diclofenac sodium. Rescues: coriander seed, mustard oil, apple vinegar, dihydroergotamine find more (DHE) intramuscular (IM), promethazine, and parenteral ketorolac. We often see patients who report having tried “everything under the sun.” If you work in a secondary or tertiary headache center, it is rare to see a patient who has not tried “the usual suspects.” And while we might not see as elaborate an alternative treatment strategy as AG presents, many of us will have

seen some or all of these in one or another patient. If not, then your entire patient population is made of the more than 50% of patients who never tell their physicians about their complementary and alternative treatments.[3] But what do we tell a patient who comes to us Ku-0059436 with this kind of a story? The clinical history

seems pretty straightforward, yet she is presenting with a treatment strategy that bears little resemblance to anything in our training. More importantly, what do we even know about many of the substances AG is ingesting? Some of the more common responses that have been reported to me by my patients (when they come to me for the third or twenty-third opinion) are: There is no scientific basis for these “so-called” natural cures. Stop them, you’re wasting your money and might even be harming yourself. Have you considered seeing a Pain Psychologist? Generally, when a patient goes to

such extremes, there is some underlying psychiatric issue. There is a variety of prescription medications that may be more effective for you, and these other things you are taking might be interfering with the real medicines, making them ineffective. While there may be an element of truth in each of these responses, they all beg the issue, and not very subtly, that most of us have no clue what most of these substances are or what they do and don’t do, why they might be prescribed, and whether they are likely to interact with prescription medicines that are being taken at the same time. Obviously, this website we cannot be expected to know about every treatment option in every medical system under the sun. The armamentarium of the homeopathic or Classical Chinese healer or Ayurvedic doctor is every bit as complex as that used in Western medicine. Each practitioner is obligated to provide enough information to allow our patients to make informed decisions about their health care. Moreover, we need to know enough about different therapies to help protect our patients from potentially dangerous practices, and finally, we need to be as non-judgmental as possible without compromising our own critical thinking. A description of Ayurvedic medicine is included in this issue by Dr. Trupti Gokani.

Abortives: peppermint oil, lavender, passion flower, rosemary, chamomile, rose hips, valerian, boswellia, rizatriptan, diclofenac sodium. Rescues: coriander seed, mustard oil, apple vinegar, dihydroergotamine this website (DHE) intramuscular (IM), promethazine, and parenteral ketorolac. We often see patients who report having tried “everything under the sun.” If you work in a secondary or tertiary headache center, it is rare to see a patient who has not tried “the usual suspects.” And while we might not see as elaborate an alternative treatment strategy as AG presents, many of us will have

seen some or all of these in one or another patient. If not, then your entire patient population is made of the more than 50% of patients who never tell their physicians about their complementary and alternative treatments.[3] But what do we tell a patient who comes to us STI571 in vitro with this kind of a story? The clinical history

seems pretty straightforward, yet she is presenting with a treatment strategy that bears little resemblance to anything in our training. More importantly, what do we even know about many of the substances AG is ingesting? Some of the more common responses that have been reported to me by my patients (when they come to me for the third or twenty-third opinion) are: There is no scientific basis for these “so-called” natural cures. Stop them, you’re wasting your money and might even be harming yourself. Have you considered seeing a Pain Psychologist? Generally, when a patient goes to

such extremes, there is some underlying psychiatric issue. There is a variety of prescription medications that may be more effective for you, and these other things you are taking might be interfering with the real medicines, making them ineffective. While there may be an element of truth in each of these responses, they all beg the issue, and not very subtly, that most of us have no clue what most of these substances are or what they do and don’t do, why they might be prescribed, and whether they are likely to interact with prescription medicines that are being taken at the same time. Obviously, see more we cannot be expected to know about every treatment option in every medical system under the sun. The armamentarium of the homeopathic or Classical Chinese healer or Ayurvedic doctor is every bit as complex as that used in Western medicine. Each practitioner is obligated to provide enough information to allow our patients to make informed decisions about their health care. Moreover, we need to know enough about different therapies to help protect our patients from potentially dangerous practices, and finally, we need to be as non-judgmental as possible without compromising our own critical thinking. A description of Ayurvedic medicine is included in this issue by Dr. Trupti Gokani.

This decrease was partially but significantly reversed by cotreating the cells with CPZ and NAC (Fig. 3C). To confirm the specificity of CPZ-induced cholestasis and its ROS dependency, the effects on TA efflux of 50 μM SA and 50 μM CSA, a noncholestatic drug and a potent inhibitor of BSEP, respectively, were also assessed using the same protocol. Although SA had no effect, CSA induced a strong inhibition of TA efflux

that was not prevented by NAC cotreatment (Fig. 3C). http://www.selleckchem.com/products/ldk378.html These data confirm that CPZ-induced TA efflux decrease, unlike CSA, was ROS-dependent. We analyzed by RT-qPCR changes in the expression of 20 potential target genes (Supporting Table 1) after treatment with 20 to 50 μM CPZ. These genes are major nuclear receptors (CAR,

FXR, and PXR) or key players in uptake transport (NTCP, OATP-B, OATB-C, OATP8, and OCT1), efflux transport (BCRP, BSEP, www.selleckchem.com/products/ABT-888.html multidrug resistance protein 1 [MDR1], MDR3, multidrug resistance-associated protein 2 [MRP2], MRP3, and MRP4), BA synthesis (CYP7A1, CYP8B1, and CYP27A1), and metabolism of exogenous and endogenous substances (CYP3A4 and SULT2A1). Although no effect was observed after 6-hour treatment whatever the studied concentration (data not shown), CPZ altered expression of several genes after a 24-hour exposure at 50 μM (Table 1). CPZ caused a decrease of mRNA of NTCP, CYP8B1, BSEP, and MDR3, whereas it caused an increase of MRP4 (a basolateral BA transporter) and CYP3A4 mRNA levels. No effects were observed on nuclear receptors transcripts. The lower doses of CPZ (20 and 35 μM) did not affect the measured mRNA levels except for CYP3A4. To determine the role of CPZ-induced ROS in modulation of transcripts levels, we studied the effects of a 24-hour NAC cotreatment on expression check details of NTCP, BSEP, MDR3, MRP4, CYP3A4, and CYP8B1 (Fig. 4A). Only inhibition of BSEP was prevented by a 24-hour coexposure with NAC. Moreover, most expression changes induced by CPZ,

i.e., inhibition of NTCP, MDR3, and CYP8B1 were reduced after a 48-hour cotreatment with NAC, whereas CYP3A4 was inhibited by CPZ and induced by a cotreatment with CPZ and NAC. To confirm the role of oxidative stress in these transcriptomic deregulations, we further analyzed effects of 6- and 24-hour (Fig. 4B,C) treatments of cells with 0.5-5 mM H2O2 on CPZ-affected genes. A dose-dependent decrease in NTCP, BSEP, MDR3, CYP3A4, and CYP8B1 and an increase in MRP4 and HO-1 were shown after a 24-hour exposure to H2O2. However, after 6-hour H2O2 treatment, only HO-1 was overexpressed starting at 1 mM and CYP8B1 was down-regulated with 5 mM H2O2. To assess whether CPZ affected the NTCP activity, cells were treated at different timepoints with 50 μM CPZ in the presence or absence of NAC and then incubated with [3H]-TA for 30 minutes. The NTCP activity was evaluated through measurement of intracellular accumulation of radiolabeled TA.

There was no significant difference in Tim-3+ cells among different clinical stages, Child Pugh Scores, or tumor differentiation stages (Table 1). HCC patients were divided into low (<7, n = 42) and high (>7, n = 57) groups based on the median levels of Tim-3+ cells. Log-rank analysis demonstrated that the high Tim-3-expressing group experienced shorter survival when compared to the low Tim-3-expressing group (Fig. 2E). The Tim-3+ cell number was positively Ulixertinib in vivo associated

with tumor size (P < 0.05) but no correlation to any other parameters (including age, gender, α-fetal protein level, tumor multiplicity, vascular invasion, intrahepatic metastasis, and tumor TNM stage) (Table 1). Multivariate analysis revealed that the number of Tim-3+ cells in HCC tissues was a negative prognostic factor of overall survival. To understand

the functionality of Tim-3+CD4+ T cells in HCC, we examined AZD5363 price their phenotype, cytokine profile, and cell cycling genes. We observed that Tim-3+CD4+ T cells were basically confined to CD45RA− and CD62L− T cells (Fig. 3A), suggesting that Tim-3+CD4+ T cells are memory cells. Next, we compared the in vivo proliferation potential and activation status of Tim-3+CD4+ T cells versus Tim-3−CD4+ T cells in HCC. Ki67 and HLA-DR are markers of cell proliferating and activation, respectively. There were fewer Ki67+ cells and HLA-DR+ cells in Tim-3+CD4+ T cells than Tim-3−CD4+ T cells (Fig. 3A,B). This suggests that Tim-3+CD4+ T cells

have reduced proliferation and activation potential in HCC. PD-1 has been identified as a marker for functionally exhausted T cells in HCC.7 We found that Tim-3+ and PD-1+ T cells were two different T-cell subsets with minimal overlapping in HCC. In addition, see more Tim-3+CD4+ T cells did not express interleukin (IL)-4, IL-17, or Foxp3 (Fig. 3A). Tumor-infiltrating Tim-3+CD4+ T cells expressed less IL-2 and IFN-γ as compared to Tim-3−CD4+ T cells (Fig. 3A,B). Together, the data indicate that HCC infiltrating Tim-3+CD4+ T cells are different from Foxp3+ regulatory T cells, functionally exhausted PD-1+ cells, and Th2 and Th17 cells. Tim-3+CD4+ T cell is a unique T-cell population with poor effector function and reduced proliferating potential in HCC. Low expression of CD28 and high expression of CD57 are thought to be associated with T-cell senescence.38 To determine if Tim-3 expression is linked to T-cell senescence in HCC, we examined the relationship between the expression of CD28, CD57, and Tim-3 on tumor-infiltrating T cells. We showed that there were more CD57+CD28− cells and fewer CD57−CD28+ cells in tumor-infiltrating Tim-3+CD4+ T cells than Tim-3−CD4+ T cells (Fig. 3C). The results suggest that Tim-3+CD4+ T cells may contain senescent cells with limited proliferating potential. Given that Tim-3+CD4+ T cells were less proliferative and contained senescent cells, we further quantified the expression of key genes controlling cell cycle and cellular senescence.