Protein embeddings predict binding residues in disordered regions.

The identification of protein binding residues helps to understand their biological processes as protein function is often defined through ligand binding, such as to other proteins, small molecules, ions, or nucleotides. Methods predicting binding residues often err for intrinsically disordered proteins or regions (IDPs/IDPRs), often also referred to as molecular recognition features (MoRFs). Here, we presented a novel machine learning (ML) model trained to specifically predict binding regions in IDPRs. The proposed model, IDBindT5, leveraged embeddings from the protein language model (pLM) ProtT5 to reach a balanced accuracy of 57.2 ± 3.6% (95% confidence interval). Assessed on the same data set, this did not differ at the 95% CI from the state-of-the-art (SOTA) methods ANCHOR2 and DeepDISOBind that rely on expert-crafted features and evolutionary information from multiple sequence alignments (MSAs). Assessed on other data, methods such as SPOT-MoRF reached higher MCCs. IDBindT5's SOTA predictions are much faster than other methods, easily enabling full-proteome analyses. Our findings emphasize the potential of pLMs as a promising approach for exploring and predicting features of disordered proteins. The model and a comprehensive manual are publicly available at https://github.com/jahnl/binding_in_disorder .

Effect of 1,25-dihydroxyvitamin D3-glycosides on postpartum health, uterine involution and litter performance of sows in a free farrowing system.

BACKGROUND: Vitamin D is essential for the reproductive efficiency in animals. There are indications that 1,25-vitD influenced the farrowing process and thus can decrease postpartum health problems. Therefore, the aim of this study was to investigate the effect of 1,25-vitD on postpartum health of the sow and uterine involution as well as the litter performance. RESULTS: The rectal body temperature in the 1,25-vitD group was significantly (p < 0.05) lower during the first five days after farrowing compared to the negative control group (D1: 38.6 vs. 38.9 °C; D2: 38.5 vs. 38.7 °C; D3: 38.4 vs. 38.7 °C; D4: 38.4 vs. 38.6 °C; D5: 38.5 vs. 38.9 °C). Although there was no difference between the live born piglets after farrowing, a significant higher number of piglets at day 7 and at weaning (Dw) was detected in the 1,25-vitD group compared to the control group (D7: 14.1 ± 0.9 vs. 13.4 ± 1.0, p = 0.002; Dw: 14.0 ± 0.9 vs. 13.4 ± 1.0, p = 0.02). Furthermore, the litter weight gain was significantly higher in the 1,25-vitD group when compared to the control group (94.3 vs. 86.4 kg; p = 0.045), and the weight loss of the sows was significantly lower (52 vs. 59 kg; p = 0.03). No differences in other parameter were detected. CONCLUSION: This study showed a positive effect of 1,25-vitD on the body temperature, the litter performance and the body condition of the sows during lactation in comparison with the negative control group. However, more studies are needed to describe the mechanism of 1,25-vitD in detail.

Effect of 1,25-Dihydroxyvitamin D3-Glycosides on the Farrowing Process and Piglet Vitality in a Free Farrowing System.

Vitamin D improves the reproductive efficiency in animals. This study aimed to examine the effects of 1,25-dihydroxyvitamin D3-gylcosides (1,25-vitD) on the farrowing process in sows and the vitality of their piglets. In total, 100 sows were allocated into two groups at insemination ('1,25-vitD' and 'negative control'). The 1,25-vitD group received 260−300 mg/sow/day 1,25-vitD in their feed during the gestation period. Backfat thickness, fecal score, and the farrowing process was evaluated. The piglets were categorized into live born or stillborn, and vitality was evaluated by assessing the umbilical cord and the meconium score. The number of total-born piglets in sows of '1,25-vitD' was higher and the farrowing duration was shorter than in the negative control group without showing significance in the univariable analysis. In a linear multiple regression model including the variables 'farrowing duration', 'total born piglets' and '1,25-vitD' differences became evident. We found that 1,25-vitD was associated with a reduced farrowing duration (p = 0.055). Moreover, significantly more mummies (p < 0.01) and short ruptured umbilical cords (p < 0.05) were observed in the 1,25-vitD group. This study showed an effect of 1,25-vitD on the farrowing process. However, more research is needed to better describe the mechanism of 1,25-vitD in detail.

Rate, Factors, and Outcome of Delayed Graft Function After Kidney Transplantation of Deceased Donors.

BACKGROUND: Delayed graft function (DGF) is a frequent complication after kidney transplantation affecting long-term outcome. PATIENTS AND METHODS: A total of 525 consecutive recipients (age 54.2 ± 13.4 years, 33% female) of kidneys from deceased donors transplanted between 2005 and 2012 were retrospectively examined. DGF was defined as the need of dialysis within the first week after transplantation. RESULTS: DGF developed in 21.1% (n = 111). Factors associated with DGF (P ≤ .035, respectively) were recipient body mass index, C-reactive protein of the recipient, residual diuresis, cold ischemia time, donor age, and diuresis in the first hour after transplantation. Median duration of DGF was 16 (2-66) days. Patients after DGF had a significantly lower GFR compared with recipients without DGF either after 3 (32.9 ± 16.5 vs 46.3 ± 18.4 mL/min/1.73 m2) or after 12 months (38.9 ± 19.3 vs 48.6 ± 20.4 mL/min/1.73 m2, P < .001, resp.). During DGF, 12.4% developed BANFF II and 18.0% BANFF I rejection, 20.2% had signs of transplant glomerulitis (first biopsy), and 16.2% (n = 18) remained on dialysis. CONCLUSION: DGF affects 1 out of 5 kidney transplants from deceased donors. Minimizing modifiable risk factors, in particular immunologic risk, may ameliorate the incidence and outcome of DGF. The outcome of DGF depends mainly on the diagnosis of any rejection and worsens upon detection of transplant glomerulitis and pronounced interstitial fibrosis and tubular atrophy (IFTA).

Speckle Tracking Echocardiography and All-Cause and Cardiovascular Mortality Risk in Chronic Kidney Disease Patients.

BACKGROUND AND OBJECTIVES: Patients with chronic kidney disease (CKD) exhibit a highly increased risk of cardiovascular (CV) morbidity and mortality. Subtle changes in left ventricular function can be detected by two-dimensional (2D) speckle tracking echocardiography (STE). This study investigated whether myocardial dysfunction detected by 2D STE may aid in CV and all-cause mortality risk assessment in patients with CKD stages 3 and 4. METHOD: A study group of 285 patients (CKD 3: 193 patients; CKD 4: 92 patients) and a healthy control group (34 participants) were included in the retrospective study. 2D STE values as well as early and late diastolic strain rates were measured in ventricular longitudinal, circumferential and radial directions. Patients' CV and all-cause outcome was determined. RESULTS: In the CKD group all measured longitudinal STE values and radial strain were significantly reduced compared to the control group. Cox proportional hazards regression revealed global longitudinal strain to predict CV and all-cause mortality (hazard ratio [HR] 1.15, 95% CI 1.06-1.25; p = 0.0008 and HR 1.09, 95% CI 1.04-1.14; p = 0.0003). After adjustment for sex, age, diabetes, estimated glomerular filtration rate, and preexisting CV disease, this association was maintained for CV mortality and all-cause mortality (HR 1.16, 95% CI 1.06-1.27; p = 0.0019 and HR 1.08, 95% CI 1.03-1.14; p = 0.0026, respectively). CONCLUSIONS: The present study shows that 2D STE detects reduced left ventricular myocardial function and allows the prediction of CV and all-cause mortality in patients at CKD stages 3 and 4.