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The ubiquitin-proteasome system (UPS) is critical for maintaining proteostasis, influencing stress resilience, lifespan, and thermal adaptability in organisms. In Caenorhabditis elegans, specific proteasome subunits and activators, such as RPN-6, PBS-6, and PSME-3, are associated with heat resistance, survival at cold (4°C), and enhanced longevity at moderate temperatures (15°C). Previously linked to improving proteostasis, we investigated the impact of sterility-inducing floxuridine (FUdR) on UPS functionality under proteasome dysfunction and its potential to improve cold survival. Our findings reveal that FUdR significantly enhances UPS activity and resilience during proteasome inhibition or subunit deficiency, supporting worms' normal lifespan and adaptation to cold. Importantly, FUdR effect on UPS activity occurs independently of major proteostasis regulators and does not rely on the germ cells proliferation or spermatogenesis. Instead, FUdR activates a distinct detoxification pathway that supports UPS function, with GST-24 appearing to be one of the factors contributing to the enhanced activity of the UPS upon knockdown of the SKN-1-mediated proteasome surveillance pathway. Our study highlights FUdR unique role in the UPS modulation and its crucial contribution to enhancing survival under low-temperature stress, providing new insights into its mechanisms of action and potential therapeutic applications.

Abstract Klebsiella pneumoniae (KP) is a nosocomial pathogen causing difficult-to-treat infections. The presence of virulence genes and antibiotic resistance of 109 KP isolates from hospitalized patients were investigated. Among them, 68.8% were multi-drug resistant (MDR) and 59.6% produced extended‐spectrum beta‐lactamases (ESBLs). Metallo-β-lactamases (MBLs) were produced by 22% of isolates (mainly from anus), including 16.5% of isolates producing New Delhi metallo-β-lactamase (NDM-1). The genes encoding adhesins (fimH—91.7%, mrkD—96.3%), enterobactin (entB—100%) and yersiniabactin (irp-1—88%) were frequently identified. The genes encoding salmochelin (iroD—9.2%, iroN—7.3%) and colibactin (clbA, clbB—0.9%) were identified rarely. Iron acquisition system-related kfu gene and wcaG gene involved in capsule production were identified in 6.4% and 11% of isolates, respectively. The rmpA gene associated with hypermucoviscosity was present in 6.4% of isolates. In 19.2% of isolates magA gene was detected, specific for K1 capsule serotype, while 22.9% of isolates showed K2 capsule serotype. The rmpA, iroD or iroN genes being diagnostic biomarkers for hypervirulent KP (hvKP) were detected in 16.5% of isolates. We found that 55.5% of hvKP were MDR and produced ESBLs, thus hospital KP isolates pose a serious threat to the healthcare system.

Abstract Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for hard-to-treat infections. The presence of 19 virulence genes in 120 MRSA isolates obtained from hospitalized patients and genetic relationships of these isolates were investigated. The eno (100%) and ebps (93.3%) genes encoding laminin- and elastin binding proteins, respectively, were ubiquitous. Other adhesion genes: fib (77.5%), fnbB (41.6%), bbp (40.8%), cna (30.8%) encoding proteins binding fibrinogen, fibronectin, bone sialoprotein and collagen, respectively, and map/eap (62.5%), encoding Eap, were also frequent. The etB and etD genes, encoding exfoliative toxins, were present in 15.6% and 12.5% isolates, respectively. The splA, splE and sspA, encoding serine protease were detected in 100%, 70.8% and 94.2% isolates, respectively. The tst gene, encoding toxic shock syndrome toxin-1 was found in 75% isolates. The cna, map/eap and tst genes were the most common in wound isolates and much less common in blood isolates. We identified 45 different spa types, t003 (21.7%) and t008 (18.8%) being the most common. The t003 was the most frequent among isolates from the respiratory tract (35.5%), while t008 in blood isolates (40%). Identification of virulence factors of MRSA is important for evaluation of pathogen transmission rate and disease development.

Snapping hip syndrome is an audible or palpable snap in a hip joint during movement which may be accompanied by pain or locking. It is typically seen in young athletes performing activities requiring repeated extreme movements of the hip. It may also follow a physical trauma, intramuscular injections or surgeries. There are two main forms of snapping hip: extra- or intra-articular. Extra-articular snapping hip is elicited by an abnormal movement of specific tendons and is divided into two forms: internal and external. The internal form of snapping hip syndrome is attributed to an abrupt movement of an iliopsoas tendon against an iliopectineal eminence. Radiograph results in patients with this form of snapping tend to be normal. Dynamic ultrasound is the gold standard diagnostic technique in both forms of extra-articular snapping hip syndrome. The objective of the following text is to describe a step-by-step dynamic ultrasonography examination in internal extra-articular snapping hip syndrome in accordance to the proposed checklist protocol. To evaluate abrupt movement of an involved tendon, the patient needs to perform specific provocation tests during the examination. With its real-time imaging capabilities, dynamic ultrasonography detects the exact mechanism of the abnormal tendon friction during hip movement in a noninvasive way. It also allows for a diagnosis of additional hip tissue changes which may be causing the pain.

Yersinia enterocolitica is a foodborne pathogen which is primarily responsible for gastrointestinal infections. The presence of the virulence genes in Y. enterocolitica strains isolated from children and antimicrobial resistance was studied in this work. The PCR, biotyping and disc diffusion method were used for analysis of Y. enterocolitica strains. Most of Y. enterocolitica strains belonged to biotype 4 and all carried ail, myfA and ystaA genes. Most of them also had the plasmid yadA gene. These genes were also detected in the strains of biotype 2, while in the two strains of biotype 1A only myfA gene was found. The blaA gene was present in all the strains of biotype 4 and 2, while blaB in the strains of biotype 2 and in some of biotype 4 strains. The presence of β-lactamase genes in Y. enterocolitica was not detected in biotype 1A. All strains were resistant to ampicillin, 76.2% and 47.6% were resistant to ticarcillin and piperacillin, respectively. Two strains (9.5%) were resistant to amoxicillin/ clavulanic acid and aztreonam, three (14.3%) to chloramphenicol, four (19%) to amikacin and trimethoprim/sulfamethoxazole, six (28.6%) to gentamicin. A few strains of Y. enterocolitica were multidrug resistant. The Y. enterocolitica strains isolated from the faeces of children suffering from diarrhea carried virulence genes and some of them were resistant to antibiotics used in extra-intestinal yersiniosis treatment. DOI: http://dx.doi.org/10.5281/zenodo.1064835

Cancer cells can undergo stress-induced premature senescence, which is considered to be a desirable outcome of anticancer treatment. However, the escape from senescence and cancer cell repopulation give rise to some doubts concerning the effectiveness of the senescence-induced anticancer therapy. Similarly, it is postulated that polyploidization of cancer cells is connected with disease relapse. We postulate that cancer cell polyploidization associated with senescence is the culprit of atypical cell divisions leading to cancer cell regrowth. Accordingly, we aimed to dissociate between these two phenomena. We induced senescence in HCT 116 cells by pulse treatment with doxorubicin and observed transiently increased ploidy, abnormal nuclear morphology, and various distributions of some proteins (e.g., p21, Ki-67, SA-β-galactosidase) in the subnuclei. Doxorubicin-treated HCT 116 cells displayed an increased production of reactive oxygen species (ROS) possibly caused by an increased amount of mitochondria, which are characterized by low membrane potential. A decrease in the level of ROS by Trolox partially protected the cells from polyploidization but not from senescence. Interestingly, a decreased level of ROS prevented the cells from escaping senescence. We also show that MCF7 cells senesce, but this is not accompanied by the increase of ploidy upon doxorubicin treatment. Moreover, they were stably growth arrested, thus proving that polyploidy but not senescence per se enables to regain the ability to proliferate. Our preliminary results indicate that the different propensity of the HCT 116 and MCF7 cells to increase ploidy upon cell senescence could be caused by a different level of the mTOR and/or Pim-1 kinases.