We hypothesize that fertility disorders in patients with aberrant expression of Cysteine-RIch Secretory Protein 2 (CRISP2) could be linked to the proposed functional role of this protein in ...fertilization.
Our in vivo and in vitro observations reveal that Crisp2-knockout mice exhibit significant defects in fertility-associated parameters under demanding conditions, as well as deficiencies in sperm fertilizing ability, hyperactivation development and intracellular Ca(2+) regulation.
Testicular CRISP2 is present in mature sperm and has been proposed to participate in gamete fusion in both humans and rodents. Interestingly, evidence in humans shows that aberrant expression of CRISP2 is associated with male infertility.
A mouse line carrying a deletion in the sixth exon of the Crisp2 gene was generated. The analyses of the reproductive phenotype of Crisp2(-/-) adult males included the evaluation of their fertility before and after being subjected to unilateral vasectomy, in vivo fertilization rates obtained after mating with either estrus or superovulated females, in vitro sperm fertilizing ability and different sperm functional parameters associated with capacitation such as tyrosine phosphorylation (by western blot), acrosome reaction (by Coomassie Blue staining), hyperactivation (by computer-assisted sperm analysis) and intracellular Ca(2+) levels (by flow cytometry).
Crisp2(-/-) males presented normal fertility and in vivo fertilization rates when mated with estrus females. However, the mutant mice showed clear defects in those reproductive parameters compared with controls under more demanding conditions, i.e. when subjected to unilateral vasectomy to reduce the number of ejaculated sperm (n = 5; P< 0.05), or when mated with hormone-treated females containing a high number of eggs in the ampulla (n ≥ 5; P< 0.01). In vitro fertilization studies revealed that Crisp2(-/-) sperm exhibited deficiencies to penetrate the egg vestments (i.e. cumulus oophorus and zona pellucida) and to fuse with the egg (n ≥ 6; P< 0.01). Consistent with this, Crisp2-null sperm showed lower levels of hyperactivation (n = 7; P< 0.05), a vigorous motility required for penetration of the egg coats, as well as a dysregulation in intracellular Ca(2+) levels associated with capacitation (n = 5; P< 0.001).
The analysis of the possible mechanisms involved in fertility disorders in men with abnormal expression of CRISP2 was carried out in Crisp2 knockout mice due to the ethical and technical problems inherent to the use of human gametes for fertilization studies.
Our findings in mice showing that Crisp2(-/-) males exhibit fertility and fertilization defects under demanding conditions support fertilization defects in sperm as a mechanism underlying infertility in men with aberrant expression of CRISP2. Moreover, our observations in mice resemble the situation in humans where fertility disorders can or cannot be detected depending on the accumulation of own individual defects or the fertility status of the partner. Finally, the fact that reproductive defects in mice are masked by conventional mating highlights the need of using different experimental approaches to analyze male fertility.
This study was supported by the World Health Organization (H9/TSA/037), the National Research Council of Argentina (PIP 2009-290), the National Agency for Scientific and Technological Promotion of Argentina (PICT 2011, 2023) and the Rene Baron Foundation to P.S.C. and by the MEXT of Japan to M.I. The authors declare that there are no conflicts of interest.
Living donor kidney transplant relieves the disease burden of patients with end-stage renal disease but may shorten donor life expectancy; however, their quality of life (QOL) is preserved. ...Nevertheless, the magnitude of the net gain of this procedure is unknown. We evaluated the QOL of both donors and recipients concurrently and calculated the net utility gain.
We recruited 210 subjects who visited the kidney transplantation clinic of a university hospital. Subjects were asked to complete the 5-level EQ-5D-based questionnaire, and patient characteristics were extracted from their medical records. We performed multivariate tobit models analysis to evaluate the QOL change caused by transplant surgery and subsequently ran computational simulations to determine the net utility gains of donors and recipients. We also performed sensitivity analyses.
After excluding 16 answers with missing data, we analyzed 203 answers in total. After the transplant surgery, recipients gained 0.07 in utility value while donors lost 0.04. In the net utility analysis, we found that the quality-adjusted life years gained ranged from 7.2 to 7.8 in the most favorable case observed in the combination of middle-aged recipients and elderly donors. Assuming no utility discount, the most favorable combination was that with older donors and younger recipients.
These findings indicated that the QOL improvement in recipients was larger than the loss among donors. When calculating the net utilities, a combination of middle-aged recipients and elderly donors yielded the largest net utility, but this was likely derived from assumption in the discount of QOL.
Lin28 is a negative regulator of the tumour suppressor microRNA, let-7, suggesting its role in tumourigenesis. However, the clinical significance of Lin28 expression in oesophageal cancer has not ...been elucidated.
Lin28 and Lin28B expression was examined by immunohistochemistry in 161 tissues from patients with oesophageal cancer who had undergone curative surgery. The relationship between the expressions of Lin28 and Lin28B and various clinicopathological factors was examined. In vitro assays were conducted to determine the role of Lin28 in aggressiveness of oesophageal cancers using oesophageal cancer cell line.
Lin28 and Lin28B were overexpressed in oesophageal cancer cells compared with non-cancerous epithelial cells, especially in the invasive front. High expression of Lin28 and Lin28B correlated significantly with lymph node metastasis and poor prognosis. High expression of Lin28B expression correlated significantly with low expression of let-7. Multivariate analysis also identified Lin28B expression as an independent prognostic factor. In vitro assays showed that the proliferative and invasive activities were significantly reduced in Lin28B-knockdown cells, compared with control cells.
High expression of Lin28 is associated with poor prognosis and high tumour aggressiveness in oesophageal cancer and these effects are mediated through increased proliferation and invasiveness of oesophageal cancer cells.
We search for lepton-flavor-violating τ→ℓV0 decays, where ℓ is an electron or muon and V0 is one of the vector mesons ρ0, ϕ, ω, K⁎0 and K¯⁎0. We use 854 fb−1 of data collected with the Belle detector ...at the KEKB asymmetric-energy e+e− collider. No evidence for a signal is found in any decay mode, and we obtain 90% confidence level upper limits on the individual branching fractions in the range (1.2–8.4)×10−8.
We report the results of a high-statistics search for H dibaryon production in inclusive Υ(1S) and Υ(2S) decays. No indication of an H dibaryon with a mass near the M(H)=2m(Λ) threshold is seen in ...either the H→Λpπ(-) or ΛΛ decay channels and 90% confidence level branching-fraction upper limits are set that are between one and two orders of magnitude below the measured branching fractions for inclusive Υ(1S) and Υ(2S) decays to antideuterons. Since Υ(1S,2S) decays produce flavor-SU(3)-symmetric final states, these results put stringent constraints on H dibaryon properties. The results are based on analyses of 102 million Υ(1S) and 158 million Υ(2S) events collected with the Belle detector at the KEKB e(+)e(-) collider.
A
bstract
We report the measurement of the two-photon decay width of
χ
c
2
(1
P
) in two-photon processes at the Belle experiment. We analyze the process
γγ
→
χ
c
2
(1
P
) →
J/ψγ
,
J/ψ
→
ℓ
+
ℓ
−
(
ℓ
...=
e
or
μ
) using a data sample of 971 fb
−
1
collected with the Belle detector at the KEKB
e
+
e
−
collider. In this analysis, the product of the two-photon decay width of
χ
c
2
(1
P
) and the branching fraction is determined to be
Γ
γγ
χ
c
2
1
P
B
χ
c
2
1
P
→
J
/
ψγ
B
J
/
ψ
→
ℓ
+
ℓ
−
=
14.8
±
0.3
stat
.
±
0.7
syst
.
eV, which corresponds to Γ
γγ
(
χ
c
2
(1
P
)) = 653
±
13(stat.)
±
31(syst.)
±
17(B.R.) eV, where the third uncertainty is from
B
(
χ
c
2
(1
P
)
→ J/ψγ
) and
B
(
J/ψ → ℓ
+
ℓ
−
).
We report the first observation of e;{+}e;{-}-->Upsilon(1S)pi;{+}pi;{-}, Upsilon(2S)pi;{+}pi;{-}, and first evidence for e;{+}e;{-}-->Upsilon(3S)pi;{+}pi;{-}, Upsilon(1S)K+K-, near the peak of the ...Upsilon(5S) resonance at sqrts approximately 10.87 GeV. The results are based on a data sample of 21.7 fb;{-1} collected with the Belle detector at the KEKB e;{+}e;{-} collider. Attributing the signals to the Upsilon(5S) resonance, the partial widths Gamma(Upsilon(5S)-->Upsilon(1S)pi;{+}pi;{-})=0.59+/-0.04(stat)+/-0.09(syst) MeV and Gamma(Upsilon(5S)-->Upsilon(2S)pi;{+}pi;{-})=0.85+/-0.07(stat)+/-0.16(syst) MeV are obtained from the observed cross sections. These values exceed by more than 2 orders of magnitude the previously measured partial widths for dipion transitions between lower Upsilon resonances.
We report the first observation of the double strange baryon Ξ(1620)^{0} in its decay to Ξ^{-}π^{+} via Ξ_{c}^{+}→Ξ^{-}π^{+}π^{+} decays based on a 980 fb^{-1} data sample collected with the Belle ...detector at the KEKB asymmetric-energy e^{+}e^{-} collider. The mass and width are measured to be 1610.4±6.0(stat)_{-4.2}^{+6.1} (syst) MeV/c^{2} and 59.9±4.8(stat)_{-7.1}^{+2.8}(syst) MeV, respectively. We obtain 4.0σ evidence of the Ξ(1690)^{0} with the same data sample. These results shed light on the structure of hyperon resonances with strangeness S=-2.
PDF
