bluuebunny/crossref_metadata_2025 huggingface dataset:
MITOL regulates phosphatidic acid-binding activity of RMDN3/PTPIP51
Authors: Ito Naoki , Takahashi Takara , Shiiba Isshin , Nagashima Shun , Inatome Ryoko , Yanagi Shigeru
Published: December 2021

The transfer of phospholipids from the endoplasmic reticulum (ER) to mitochondria via the mitochondria-ER contact site (MERCS) is essential for maintaining mitochondrial function and integrity. Here, we identified RMDN3/PTPIP51, possessing phosphatidic acid (PA)-transfer activity, as a neighbouring protein of the mitochondrial E3 ubiquitin ligase MITOL/MARCH5 by proximity-dependent biotin labelling using APEX2. We found that MITOL interacts with and ubiquitinates RMDN3. Mutational analysis identified lysine residue 89 in RMDN3 as a site of ubiquitination by MITOL. Loss of MITOL or the substitution of lysine 89 to arginine in RMDN3 significantly reduced the PA-binding activity of RMDN3, suggesting that MITOL regulates the transport of PA to mitochondria by activating RMDN3. Our findings imply that ubiquitin signalling regulates phospholipid transport at the MERCS.
Bridging the Gender Participatory Gap in Water and Sanitation Rights Adjudication
Authors: Nankan Sahara
Published: December 2021

This article critically examines the justifications, litigation strategies, adjudicatory mechanisms and implications for strengthening gender participatory processes in domestic enforcement of the separate but critically interlinked rights to basic water and adequate sanitation services. The article first examines how the lack of women’s full, free and meaningful participation as key stakeholders both causes and contributes to gendered deprivation by examining three early leading jurisprudential examples from South Africa, Mazibuko and Others v City of Johannesburg (2009), Nokotyana and Others v Ekurhuleni Municipality (2009) and Beja and Others v Premier of the Western Cape (2011). Employing the literature on principles of adjudication and the discourse on equality, gender and dignity, the concept of ‘gender-responsive participatory justice’ (GPJ) is then put forth as a flexible analytical and strategic tool to mitigate the ad hoc gender-sensitive considerations that remain wholly inadequate to guaranteeing equality and non-discrimination commitments in practice. In doing so, the article emphasizes the critical nexus between procedure and the substantive values and functions of these rights in the form of autonomy-based equality and agency-based dignity. In the final instance, this examination is operationalized by a preliminary applied discussion of how gender-responsive deliberative principles of participation and their accompanying values can be utilized by practitioners and policy-makers to ultimately pursue proactive ways of guaranteeing that women’s participation becomes fully integrated in water and sanitation rights implementation.
Chinese court rules for the first time that it has jurisdiction over SEP global licensing disputes
Authors: Jin Yan , Wang Chao
Published: December 2021

OPPO v Sharp Corporation: Jurisdictional Objection in Global Rate Setting of Standard Essential Patent ((2020) Zui Gao Fa Zhi Min Xia Zhong No. 517), 19 August 2021

The Intellectual Property Court of the Supreme People’s Court (SPC) of China ruled that Chinese courts have jurisdiction over global licensing terms disputes for standard essential patent (SEP) in the communications sector.
Duplicated gallbladder with double cystic duct: hidden in plain sight
Authors: Poh Wei S , Menon Tulsi , Wijesuriya Ruwan , Misur Philip
Published: December 2021

Duplicated gallbladder with double cystic duct is a rare anomaly, with 62 cases reported including this case. We present a 76-year-old man who underwent interval laparoscopic cholecystectomy after previous conservative management of acute cholecystitis. Retrograde dissection of gallbladder was performed due to difficult access. Gallbladder was opened at Hartman’s pouch which revealed two bile-flowing structures. Cholangiogram was only successful via one of the ducts with no evidence of leak. Subtotal cholecystectomy was performed after consultation with a Hepatobiliary surgeon. Preoperative computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP) were reviewed which revealed duplicated gallbladder. CT cholangiogram was performed post-operatively, confirming two separate cystic ducts. Our case emphasizes that anatomical anomalies can still be unappreciated despite having high-resolution CT and MRCP preoperatively, which poses increased risk of biliary tree injury. Routine intraoperative cholangiogram will help avoid bile duct injuries. Literature advises that both gallbladders should be removed to avoid relapse of gallbladder disease.
SDSS-IV MaNGA: integral-field kinematics and stellar population of a sample of galaxies with counter-rotating stellar discs selected from about 4000 galaxies
Authors: Bevacqua Davide , Cappellari Michele , Pellegrini Silvia
Published: December 2021

We present the integral-field kinematics and stellar population properties of 64 galaxies (61 are Early-Type galaxies; ETGs) with Counter-Rotating stellar Disks (CRD) selected from about 4000 galaxies in the MaNGA survey, based on evidence of counter-rotation or two velocity dispersion peaks in the kinematic maps. For 17 CRDs, the counter-rotating components can also be separated spectroscopically. The frequency of CRDs in MaNGA is <5 per cent for ellipticals, <3 per cent for lenticulars, and <1 per cent for spirals (at 95 per cent confidence level), consistent with previous estimates. We produced age and metallicity maps, and compared the stellar population properties to those of the general ETGs population. We found that CRDs have similar trends in age and metallicity to ETGs, but are less metallic at low masses, and show flatter age and steeper metallicity gradients, on average. A comparison of the velocity fields of the ionized gas and the stars reveals that in 33 cases the gas corotates with either the inner (15 cases) or outer (18 cases) stellar disc, and in nine cases it is misaligned. In most cases the gas corotates with the younger disc. Evidence of multimodality in the stellar population is found in 31 galaxies, while the 14 youngest and least massive galaxies show ongoing star formation; 14 galaxies, instead, exhibit unimodality, and are the oldest and most massive. As a general result, our work indicates that CRDs form primarily via gas accretion in retrograde rotation with respect to a pre-existing stellar disc.
Copper toxicity towardsCampylobacter jejuniis enhanced by the nickel chelator dimethylglyoxime
Authors: Benoit Stéphane L , Maier Robert J
Published: December 2021

The nickel (Ni)-chelator dimethylglyoxime (DMG) was found to be bacteriostatic towards Campylobacter jejuni. Supplementation of nickel to DMG-containing media restored bacterial growth, whereas supplementation of cobalt or zinc had no effect on the growth inhibition. Unexpectedly, the combination of millimolar levels of DMG with micromolar levels of copper (Cu) was bactericidal, an effect not seen in select Gram-negative pathogenic bacteria. Both the cytoplasmic Ni-binding chaperone SlyD and the twin arginine translocation (Tat)-dependent periplasmic copper oxidase CueO were found to play a central role in the Cu-DMG hypersensitivity phenotype. Ni-replete SlyD is needed for Tat-dependent CueO translocation to the periplasm, whereas Ni-depleted (DMG-treated) SlyD is unable to interact with the CueO Tat signal peptide, leading to mislocalization of CueO and increased copper sensitivity. In support of this model, C. jejuni ΔslyD and ΔcueO mutants were more sensitive to copper than the wild-type (WT); CueO was less abundant in the periplasmic fraction of ΔslyD or DMG-grown WT cells, compared to WT cells grown on plain medium; SlyD binds the CueO signal sequence peptide, with DMG inhibiting and nickel enhancing the binding, respectively. Injection of Cu-DMG into Galleria mellonella before C. jejuni inoculation significantly increased the insect survival rate compared to the control group. In chickens, oral administration of DMG or Cu-DMG decreased and even abolished C. jejuni colonization in some cases, compared to both water-only and Cu-only control groups. The latter finding is important, since campylobacteriosis is the leading bacterial foodborne infection, and chicken meat constitutes the major foodborne source.
Activate dormant C–H bonds with tons of enthusiasm: an interview with Jin-Quan Yu
Authors: Zhao (赵维杰) Weijie
Published: December 2021

Synthetic chemistry is the art of molecules. By breaking and forming chemical bonds, chemists can transform one molecule into another, and provide a variety of chemicals that we use in our daily lives. Among all chemical bonds, the carbon-hydrogen (C–H) bond is one of the most common, and is present in almost every organic compound. Breaking C–H bonds and connecting the carbon atoms with other atoms or groups is an essential step for the synthesis of a large variety of chemicals—from bulk chemicals to functional materials and drug candidates. However, the C–H bond is extremely stable and difficult to break, and C–H activation and functionalization has been a challenging fundamental problem for decades.

Professor Jin-Quan Yu (余金权) from the Scripps Research Institute is one of the most active scientists in this field. His group developed a number of C–H activation catalysts—often consisting of metal centers and elaborately designed ligands—that drastically shorten the synthesis steps of diverse functional molecules and provide high reactivity and selectivity. Here, Professor Yu discussed with NSR the interesting field of C–H activation, as well as sharing reflections on his own research.
Reply to Edwards and Ogilvie: ‘Did the Black Death Cause Economic Development by “Inventing” Fertility Restriction’
Authors: Voigtländer Nico , Voth Hans-Joachim
Published: December 2021

This reply shows that Edwards’ and Ogilvie’s critique of our paper (Voigtländer and Voth, American Economic Review 2013) is based on a failure to understand the logic of our argument, a flawed reading of the historical evidence, and basic econometric mistakes. The validity of our assumptions, the mechanism of the model, and the strength of our empirical evidence stand as in our original publication.
Covid-19 in recipients of living donor liver transplantation: a worse or an equivalent outcome?
Authors: Salah M , Dabbous H M , Montasser I F , Bahaa M , Abdou A M H , Elmeteini M S
Published: December 2021

Background

Coronavirus disease 2019 (Covid-19) pandemic is representing a massive burden to the community with the new virus. There is few data regarding Covid-19 in liver transplant patients. Concerns were raised regarding the course of the disease in transplanted patients due to immunosuppression and risk of hepatic injuries.

Aim

To describe the outcomes of Covid-19 infection in recipients of living-donor liver transplantation (LDLT).

Methods

Retrospective analysis of 41 recipients of LDLT diagnosed with Covid-19 by real-time PCR or CT chest criteria of Covid-19 between April 2020 and April 2021. This Cohort was derived from Ain Shams Center for Organ Transplantation database, Ain Shams Specialized Hospital, Cairo, Egypt, which is considered one of the largest centers of LDLT in the Middle East. Patients were classified to mild, moderate, severe and critics according to clinical classification released by the National Health Commission of China.

Results

A total of 41 patients and 2 patients with reinfection were included in this cohort with mean age 54 years with 74% male and 26% female. The body mass index ranged from 19.3 to 37. About 30% were described as a mild case, 46.5% were moderate, 14% were severe and 9% were critical cases. Two cases developed infection twice. Total of 20 patients (46.5%) were managed in home isolation setting, 17 patients (39.5%) needed admission to ward, 4 patients (9%) in intermediate care unit and 2 patients (4%) admitted to intensive care unit. About 60% of cases were on room air, only 3 patients needed invasive methods, 2 patients needed face mask and 1 case needed invasive CPAP. In total, 41 patients recovered (95%) and 2 patients (5%) died; 1 was Covid related and the other one was non-Covid related. Female gender, higher BMI and hypertension were associated with severe course of the disease.

Conclusion

In the setting of LDLT, the possibilities of catching Covid-19 infection are high due to chronic immunosuppression use. Yet, the outcome of infection in term of morbidity and the needs for hospital admission or intensive care is generally matched to general population.
“Some Vital Religion”: Social Religion and the Science of Character Education in the United States, 1918–1932
Authors: McCamant Jane
Published: December 2021

The history of American public education has generally been considered as a steady transition from religious and sectarian to secular and pluralist, with the role of science in education increasing as the role of religion decreased. This article examines a conception of the role of religion in education that does not fit this narrative, the “social religion” of theorists of moral and character education in the 1920s. Relying on ideas of religious naturalism and with an orientation toward the practical effects of religious belief, this community of scholars asserted a concept of religion that would allow it to be at the heart of the common school project, uniting all under the common morality of the social good. Influenced both by liberal Protestant humanism and the scientific worldview pervasive in education reform at the time, these character educationists’ ideas remind us of the historical contingency of categories like “religious” and of the antiquity of ideas we might classify under the heading of spirituality in American culture.
Three Cases of Gastrointestinal Mucor Colonization in Patients With Prolonged Neutropenia
Authors: Seifer Charles M. , Logothetis Constantine N. , Greene John N.
Published: December 2021

Mucor is a well-known opportunistic organism; however, it rarely infects the gastrointestinal (GI) tract. Although known to transiently colonize healthy immunocompetent individuals, the incidence of mucormycosis is increasing in patients with hematologic malignancies, which can have serious consequences in an immunocompromised host. This abstract presents 3 patients from a single institution with Mucor colonization of their stool.

Each patient had a hematologic malignancy and was neutropenic when diagnosed with Mucor colonization of the stool. The duration of neutropenia ranged from 1 to 76 days with median of 31 days at the time of diagnosis. Patients were observed for symptoms of GI tract invasion, and they received antimold prophylaxis while neutropenic. Despite GI shedding, no mold sinusitis or pneumonia or gastroenteritis was noted. Gastrointestinal mucormycosis was never noted during their hospital course.

This case series emphasizes the importance of not dismissing mold colonization of the stool in a patient with prolonged neutropenia who is at high risk of invasive GI tract mucormycosis. When stool cultures grow Mucor in patients with prolonged neutropenia, anti-Mucor therapy is indicated and may prevent invasive mold infection during the period of risk.
A Retrospective Study of Febrile Neutropenia From a Cancer Hospital
Authors: Sukauichai Sitthi , Lamaikul Sopa
Published: December 2021

Background

Fever in neutropenic patients is considered an emergency medical condition, requiring early recognition and prompt management. The aims of this study were to find the pathogen and time to antibiotic administration, and to identify predictive factors of mortality in patients with febrile neutropenia.

Methods

We retrospectively reviewed the clinical manifestations, pathogenic organisms, treatment regimens, and 30-day mortality of febrile neutropenic adult patients with solid tumor admitted to a cancer hospital in Thailand from January 2014 to December 2019.

Results

We enrolled 96 episodes of febrile neutropenia. Median age was 53 years. Sixty-two patients (64.6%) were female. The 2 most common cancers were head and neck (31.2%), followed by breast (30.2%), and 69.8% of all patients were in the advanced stage. Seven patients (7.3%) died within 30 days after onset. Bacteremia occurred in 7 episodes (7.8%). Source of infection was identified in 21 patients (21.8%). Gram-negative organism accounted for 85% of bacteremia and 79% of isolated pathogen. Pseudomonas aeruginosa was the most frequently identified causative organism. The most common empirical antibiotic was ceftazidime (67.7%). Median time to antibiotic administration was significantly shorter for nonsurvivors (32.5 minutes) than for survivors (62.0 minutes; P = 0.031). In the multivariate analysis, sepsis (odd ratio, 10.74; 95% confidence interval, 1.93–59.73; P = 0.007) was associated with increased 30-day mortality.

Conclusions

Gram negative was the predominant pathogen of neutropenic patients in this study. Shorter time to antibiotic administration did not contribute to a better outcome. Sepsis was an unfavorable predictive factor of death.
Outcomes of Implementing an Infectious Diseases Approval of Selected Antimicrobials as an Antimicrobial Stewardship Initiative in a Referral Hospital in Iran
Authors: Karimzadeh Iman , Alhashemi Samira Hossaini , Ghetmiri Seyedeh Shima , Vazin Afsaneh
Published: December 2021

Background

The excessive use of antimicrobials over the past few decades has led to an ever-increasing spread of microbial resistance, leading to increased cost and time to treat infectious diseases. The aim of this study was to investigate the clinical and economic benefits of an antimicrobial stewardship program on prescribing 5 costly used antimicrobial drugs in a large referral teaching hospital.

Methods

This study is a quasiexperimental study that focused on the consumption of the 5 costly antimicrobial drugs, including liposomal amphotericin B, caspofungin, colistimethate sodium, linezolid, and voriconazole between preintervention and postintervention plans (2016–2018). If the antimicrobial was not approved by the infectious disease physician, possible alternative medications were used. Indexes, including total consumption rate, per capita consumption, total cost, per capita cost, mortality rate, and length of hospital stay, were measured annually.

Results

There were 29,268 and 27,704 hospitalized patients that were screened primarily. Among them, 600 patients were eligible for each preintervention and postintervention phases. After the intervention, defined daily dose dropped by 18.23%, 25.51%, 9.56%, and 31.56% for amphotericin B, colistimethate sodium, caspofungin, and voriconazole, respectively. The expenditure of restricted antimicrobials decreased by 34.98% in the postimplementation of antimicrobial stewardship program (P < 0.05). The rates of hospital mortality before (40.3%) and after the intervention (38.6%) were not significantly different (P = 0.285). There is no significant result between the mean ± SD duration of hospital stays before (40.39 ± 33.07 days) and after the intervention (36.17 ± 24.84 days; P = 0.08).

Conclusions

Our study data suggest that the active contribution of infectious diseases specialist in the antimicrobial stewardship program can significantly reduce the total cost, as well as defined daily dose of high-cost antimicrobial medications along with improving the clinical outcome.
Diagnostic Dilemma and Therapeutic Challenges in Managing an Atypical Presentation of an Ocular Toxoplasmosis Patient With Myasthenia Gravis: Literature Review
Authors: Tham Zen Kuang , Lott Pooi Wah , Ee Chye Li , Ramli Norlina , Iqbal Tajunisah
Published: December 2021

Purpose

The aim of the study was to report a case of ocular toxoplasmosis (OT) in an immunocompromised patient with myasthenia gravis, the diagnostic dilemma, and therapeutic challenges in managing the patient.

Method

This is a case report with literature review. Articles reviewed were limited to publications in English, and there were no restrictions on date, age, ethnicity, or geographic locations of patients. In addition, a brief literature review of similar reported cases was conducted to discuss about the diagnostic dilemma and therapeutic challenges in managing our patient.

Observation

We report a case of an immunocompromised, 53-year-old man who presented with rapid deterioration of left eye vision for 2 weeks. The ophthalmological examination showed nongranulomatous panuveitis with dense vitritis and retinitis with the absence of adjacent pigmented scar. Diagnostic dilemma arose as the clinical picture mimicked several possible etiologies. He was initially treated clinically as viral retinitis but failed to show improvement with antiviral treatment. Because of recent history of left empyema, he was then treated as presumed endophthalmitis and received broad-spectrum antimicrobial and antifungal therapies. He was also given oral sulfamethoxazole and trimethoprim (Bactrim) because of suspicion on OT. Despite multiple drug therapy, he still did not improve clinically. A diagnostic pars plana vitrectomy was performed and the toxoplasma polymerase chain reaction was positive. Therapeutic challenges were apparent due to limited choice of antibiotics which can be used in patients with myasthenia gravis and possible resistance to Bactrim in this case. After 6 weeks of pyrimethamine and sulfadiazine, he was clinically stable with vision of 6/60 due to macular scarring.

Conclusions

The diagnosis of atypical OT is challenging and frequently misdiagnosed as viral retinitis or endophthalmitis, leading to delayed diagnosis and treatment. Clinicians should have a high index of suspicion whenever seeing an atypical manifestation of OT in immunocompromised patients. In addition, there is very limited published data looking into the clinical presentations, diagnostic methods, treatment modalities and outcomes, specifically in reported atypical OT case reports or series. Therefore, it warrants an in-depth review to help clinician have a better understanding about this disease.
Factors Affecting Clinical Outcomes of Carbapenem-Resistant Enterobacteriaceae and Carbapenem-Susceptible Enterobacteriaceae Infections
Authors: Soontaros Suluck , Leelakanok Nattawut , Tantipong Hutsaya , Charoonwach Wacharee , Auamnoy Titinun
Published: December 2021

Background

Carbapenem-resistant Enterobacteriaceae (CRE) is currently an emerging global public health problem and has significant negative impacts in many countries. This study aimed to identify risk factors associated with the mortality and readmission of CRE- and carbapenem-susceptible Enterobacteriaceae (CSE)–infected patients in Thailand. Length of stay (LOS) and the cost of treatment for the infections were also investigated.

Method

A retrospective cohort study was conducted in patients with CRE- and CSE-positive cultures from January 2016 to June 2019 in an advanced-level government hospital in Thailand. Risk factors for mortality and readmission were analyzed by logistic regression analysis. The differences in LOS and cost of treatment between CRE- and CSE-infected patients were analyzed by the independent t test.

Results

A total of 316 and 329 of the patients that were CRE and CSE culture positive, respectively, were included. Carbapenem-resistant Enterobacteriaceae was significantly associated with 30-day mortality [adjusted odds ratio (aOR), 2.86; 95% confidence interval (CI), 1.84–4.44; P < 0.001] and with 90-day mortality (aOR, 3.11; 95% CI, 2.01–4.83; P < 0.001). Factors that increased the risk of 30-day mortality and 90-day mortality were the Charlson Comorbidity Index score, the number of days with an invasive device or indwelling line, septic shock, acute respiratory failure, site of severe infection, and moderate to severe renal impairment. Carbapenem-resistant Enterobacteriaceae was also associated with 90-day readmission rate (aOR, 3.24; 95% CI, 1.85–5.70; P < 0.001). The LOS of CRE-infected patients and CSE-infected patients was significantly different and was 29.18 ± 36.44 and 9.78 ± 12.77 days, respectively (P < 0.001). The cost of treatment in CRE- and CSE-infected patients was significantly different (P < 0.001). The cost in CRE-infected patients was 181,183.65 ± 281,325.26 baht, whereas the cost in CSE-infected patients was 53,296.75 ± 79,316.67 baht (P < 0.001). Antibiotics for CRE-specific therapy including colistin, fosfomycin, tigecycline, or aminoglycosides, that were prescribed in combination were the mainstay treatments.

Conclusions

Carbapenem-resistant Enterobacteriaceae was an independent predictor for mortality and readmission. Length of stay and cost of treatment in CRE-infected patients were significantly higher than in CSE-infected patients.
Implementation of an Emergency Department–Embedded Infusion Center for the Administration of Monoclonal Antibody Therapy in Patients With Early COVID-19 Infection
Authors: Graham Julie , Ballejos Christina , Jenkins Danisha , Kelley Christina
Published: December 2021

The coronavirus disease 2019 (COVID-19) pandemic has tested nurse staffing and other resources necessary for lifesaving treatment. The emergency use authorization in November 2020 of bamlanivimab as monotherapy and casirivimab/imdevimab as combination therapy brought hope to many as an option for outpatients at risk for severe illness. However, logistical concerns were soon revealed, because safe administration requires a location where patients can receive specialized care and monitoring for a period of 2 hours. This type of therapy would normally be offered at an outpatient infusion center. These centers often serve persons who are immunocompromised, and introducing COVID-19–positive individuals could threaten the safety of this population. This article describes the deployment of an emergency department–embedded infusion center set up for the purpose of supporting community members and providers electing for this treatment option.
Outcomes of SOT Recipients With COVID-19 in Different Eras of COVID-19 Therapeutics
Authors: Sait Afrah S. , Chiang Teresa Po-Yu , Marr Kieren A. , Massie Allan B. , Cochran Willa , Shah Pali , Brennan Daniel C. , Thomas Alvin G. , Mehta Steinke Seema , Permpalung Nitipong , Shoham Shmuel , Merlo Christian , Jain Tania , Boyarsky Brian , Charnaya Olga , Gurakar Ahmet , Sharma Kavita , Durand Christine M. , Werbel William A. , Huang Chiung-Yu , Ostrander Darin , Desai Niraj , Kim Min Young , Alasfar Sami , Bloch Evan M. , Tobian Aaron A.R. , Garonzik-Wang Jacqueline , Segev Dorry L. , Avery Robin K.
Published: December 2021

Background.

Few reports have focused on newer coronavirus disease 2019 (COVID-19) therapies (remdesivir, dexamethasone, and convalescent plasma) in solid organ transplant recipients; concerns had been raised regarding possible adverse impact on allograft function or secondary infections.

Methods.

We studied 77 solid organ transplant inpatients with COVID-19 during 2 therapeutic eras (Era 1: March–May 2020, 21 patients; and Era 2: June–November 2020, 56 patients) and 52 solid organ transplant outpatients.

Results.

In Era 1, no patients received remdesivir or dexamethasone, and 4 of 21 (19.4%) received convalescent plasma, whereas in Era 2, remdesivir (24/56, 42.9%), dexamethasone (24/56, 42.9%), and convalescent plasma (40/56, 71.4%) were commonly used. Mortality was low across both eras, 4 of 77 (5.6%), and rejection occurred in only 2 of 77 (2.8%) inpatients; infections were similar in hypoxemic patients with or without dexamethasone. Preexisting graft dysfunction was associated with greater need for hospitalization, higher severity score, and lower survival. Acute kidney injury was present in 37.3% of inpatients; renal function improved more rapidly in patients who received remdesivir and convalescent plasma. Post–COVID-19 renal and liver function were comparable between eras, out to 90 d.

Conclusions.

Newer COVID-19 therapies did not appear to have a deleterious effect on allograft function, and infectious complications were comparable.
Ischemic Cholangiopathy Postdonation After Circulatory Death Liver Transplantation: Donor Hepatectomy Time Matters
Authors: Goussous Naeem , Alvarez-Casas Josue , Dawany Noor , Xie Wen , Malik Saad , Gray Stephen H. , Barth Rolf N. , LaMattina John C.
Published: December 2021

Background.

Outcomes of liver transplantation (LT) from donation after circulatory death (DCD) have been improving; however, ischemic cholangiopathy (IC) continues to be a problem. In 2014, measures to minimize donor hepatectomy time (DHT) and cold ischemic time (CIT) have been adopted to improve DCD LT outcomes.

Methods.

Retrospective review of all patients who underwent DCD LT between 2005 and 2017 was performed. We compared outcomes of patients who were transplanted before 2014 (historic group) with those who were transplanted between 2014 and 2017 (modern group).

Results.

We identified 112 patients; 44 were in the historic group and 68 in the modern group. Donors in the historic group were younger (26.5 versus 33, P = 0.007) and had a lower body mass index (26.2 versus 28.2, P = 0.007). DHT (min) and CIT (h) were significantly longer in the historic group (21.5 versus 14, P < 0.001 and 5.3 versus 4.2, P < 0.001, respectively). Fourteen patients (12.5%) developed IC, with a significantly higher incidence in the historic group (23.3% versus 6.1%, P = 0.02). There was no difference in graft and patient survival between both groups.

Conclusion.

In appropriately selected recipients, minimization of DHT and CIT may decrease the incidence of IC. These changes can potentially expand the DCD donor pool.
High quality genome assembly of the amitochondriate eukaryote Monocercomonoides exilis
Authors: Treitli Sebastian Cristian , Peña-Diaz Priscila , Hałakuc Paweł , Karnkowska Anna , Hampl Vladimír
Published: December 2021

Monocercomonoides exilis is considered the first known eukaryote to completely lack mitochondria. This conclusion is based primarily on a genomic and transcriptomic study which failed to identify any mitochondrial hallmark proteins. However, the available genome assembly has limited contiguity and around 1.5 % of the genome sequence is represented by unknown bases. To improve the contiguity, we re-sequenced the genome and transcriptome of M. exilis using Oxford Nanopore Technology (ONT). The resulting draft genome is assembled in 101 contigs with an N50 value of 1.38 Mbp, almost 20 times higher than the previously published assembly. Using a newly generated ONT transcriptome, we further improve the gene prediction and add high quality untranslated region (UTR) annotations, in which we identify two putative polyadenylation signals present in the 3′UTR regions and characterise the Kozak sequence in the 5′UTR regions. All these improvements are reflected by higher BUSCO genome completeness values. Regardless of an overall more complete genome assembly without missing bases and a better gene prediction, we still failed to identify any mitochondrial hallmark genes, thus further supporting the hypothesis on the absence of mitochondrion.
Altered Intercellular Communication and Extracellular Matrix Signaling as a Potential Disease Mechanism in Human Hypertrophic Cardiomyopathy
Authors: Larson Amy , Codden Christina J. , Huggins Gordon S. , Rastegar Hassan , Chen Frederick Y. , Maron Barry J. , Rowin Ethan J. , Maron Martin S. , Chin Michael T.
Published: December 2021

Objectives

To understand Hypertrophic Cardiomyopathy-associated alterations in gene expression and intercellular communication at the single cell level in left ventricular outflow tract lesions.

Background

Human hypertrophic cardiomyopathy (HCM) is considered a disorder of the sarcomere (i.e., cardiomyocytes) but the paradoxical association of nonmyocyte phenotypes such as fibrosis, mitral valve anomalies and microvascular occlusion is unexplained.

Methods

To understand the interplay between cardiomyocyte and nonmyocyte cell types in human HCM, single nuclei RNA-sequencing (snRNA-seq) was performed on myectomy specimens from HCM patients with left ventricular outflow tract obstruction and control samples from donor hearts free of cardiovascular disease.

Results

Clustering analysis identified a total of 34 distinct cell populations, which were classified into 10 different cell types based on marker gene expression. Differential gene expression analysis comparing HCM to Normal datasets revealed differences in sarcomere and extracellular matrix gene expression. Analysis of expressed ligand-receptor pairs across multiple cell types indicated profound disruption in HCM intercellular communication, particularly between cardiomyocytes and fibroblasts, fibroblasts and lymphocytes and involving integrin β1 and its multiple extracellular matrix (ECM) cognate ligands.

Conclusions

These findings provide evidence for intercellular interactions in HCM that link sarcomere dysfunction with altered cardiomyocyte secretion of ECM ligands, altered fibroblast ligand-receptor interactions with a variety of cell types and increased fibroblast to lymphocyte signaling, which can further alter the ECM composition, disrupt cellular function and promote nonmyocyte phenotypes.
Prevalence of HIV and Syphilis and their Co-infection among Men Having Sex with Men in Asia: A Systematic Review and Meta-analysis
Authors: Mahmud Sultan , Mohsin Md , Muyeed Abdul , Hossain Sorif , Islam Md Mynul , Islam Ariful
Published: December 2021

Background

Studies found that the group of men who have sex with men (MSM) is at a very high level of risk of HIV and sexually transmitted infections (STIs) in Asian regions due to multiple reasons. Although the prevalence of HIV among general people in Asia is considered low, the prevalence of HIV and Syphilis among MSM in this region was found very high and usually, it goes unnoticed. This study aimed to inspect the prevalence and trends of HIV, Syphilis, and their co-infection among MSM in Asia.

Methods

A systematic search was performed on January 5, 2021, in PubMed, MEDLINE, and Google Scholar databases. To evaluate the heterogeneity, Q-tests and were used. To explore the publication bias, Eggers’ test and funnel plot were used. The random-effect model and subgroup analysis were performed due to the significant heterogeneity.

Results

A total of 2,872 articles were identified, and 66 articles of high quality were included in the final analysis. The overall prevalence of HIV among MSM and Syphilis was estimated considering 69 estimates from 66 studies whereas 19 estimates of co-infection were found in 17 studies. The pooled HIV prevalence was 8.48% (CI: 7.01-9.95) and the pooled Syphilis prevalence was 9.86% (CI: 8.30-11.41) with significant heterogeneity and publication bias. The pooled prevalence of HIV and Syphilis co-infection was 2.99% (CI: 1.70-4.27) with significant heterogeneity and no publication bias. The HIV, Syphilis, and HIV and Syphilis co-infection prevalence estimates exhibited an upward trend during 2002-2017.

Conclusions

HIV, Syphilis, and their co-infection are quite prevalent among MSM in the Asia-Pacific region. Integrated and intensified intervention strategies, HIV testing, and improved access to antiretroviral treatment as well as increased awareness are needed to reduce HIV, Syphilis, and their co-infection among the discussed vulnerable group.
Gosha: a database of organisms with defined optimal growth temperatures
Authors: Helena-Bueno Karla , Brown Charlotte R. , Melnikov Sergey
Published: December 2021

Currently, we are witnessing an explosive accumulation of genomic sequences for organisms across all branches of life. However, typically the genomic data lack the information about optimal growth conditions of corresponding organisms. As a result, it becomes challenging to use the genomic data for studying the adaptations of organisms and biological molecules to diverse environments. To address this problem, we have created a database Gosha, available athttp://melnikovlab.com/gshc. This database brings together information about the genomic sequences and optimal growth temperatures for 25,324 species, including ∼89% of the bacterial species with known genome sequences. Using this database, one can annotate genomic sequences from thousands of species and correlate variations in genes and genomes with optimal growth temperatures. The database interface allows users to retrieve optimal growth temperatures for bacteria, eukaryotes and archaea, providing a tool to explore how organisms, genomes, and individual proteins and nucleic acids adapt to certain temperatures. We hope that this database will contribute to medicine and biotechnology by helping to create a better understanding of molecular adaptations to heat and cold, leading to new ways to preserve biological samples, engineer useful enzymes, and develop biological materials and organisms with the desired tolerance to heat and cold.

GRAPHICAL ABSTRACT

Gosha (available atwww.melnikovlab.com/gshc) is a database that collects information about the optimal growth temperatures of living species. This database aims to facilitate studies of molecular adaptation to specific temperatures.

Abstract Figure
A quadratic analytical solution of root pressure generation provides insights about bamboo and other species
Authors: Yang Dongmei , Wang Xiaolin , Yin Mengqi , Zhang Yong-Jiang , Peng Guoquan , Tyree Melvin T.
Published: December 2021

We derived a steady-state model of whole root pressure generation through the combined action of all parallel segments of fine roots. This may be the first complete analytical solution for root pressure, which can be applied to complex roots/shoots.

The osmotic volume of a single root is equal to that of the vessel lumen in fine roots and adjacent apoplastic spaces. Water uptake occurs via passive osmosis and active solute uptake (, osmol s−1), resulting in the osmolal concentration Cr (mol·kg−1 of water) at a fixed osmotic volume. Solute loss occurs via two passive processes: radial diffusion of solute Km(Cr-Csoil), where Km is the diffusional constant and Csoil is the soil-solute concentration) from fine roots to soil and mass flow of solute and water into the whole plant from the end of the fine roots.

The proposed model predicts the quadratic function of root pressure , where b and c are the functions of plant hydraulic resistance, soil water potential, solute flux, and gravitational potential.

The present study investigates the theoretical dependencies of Pr on the factors detailed above and demonstrates the root pressure-mediated distribution of water through the hydraulic architecture of a 6.8-m-tall bamboo shoot.

One sentence Summary

An analytical solution for root pressure is derived and illustrated by applying it to the measured hydraulic architecture of a 7-meter bamboo shoot.
AFP2 inhibits ABA responses during germination without ABI5 degradation but DWAs reduce desiccation tolerance
Authors: Lynch Tim , Née Guillaume , Chu Avan , Krüger Thorben , Finkemeier Iris , Finkelstein Ruth R
Published: December 2021

Overexpression of ABI5/ABF interacting proteins (AFPs) results in extreme ABA resistance of seeds and failure to acquire desiccation tolerance, at least in part through effects on chromatin modification. This study tests the hypothesis that the AFPs promote germination by also functioning as adapters for E3 ligases that ubiquitinate ABI5, leading to its degradation. Interactions between AFPs and two well-characterized classes of E3 ligases targeting ABI5,DWD HYPERSENSITIVE TOABA (DWA)s and KEEP ON GOING (KEG), were analyzed by yeast two-hybrid, bimolecular fluorescence complementation, and genetic assays. Although the AFPs and E3 ligases showed weak direct interactions, loss of function for the E3 ligases did not impair ABA-resistance conferred by overexpression of the YFP-AFP2 fusion. Comparison of ABI5 and AFP2 levels in these lines showed that AFP2 accumulation increased during germination, but that ABI5 degradation followed germination, demonstrating that AFP2 controls ABA sensitivity during germination independently of ABI5 degradation. Surprisingly, AFP2 overexpression in thedwa1 dwa2mutant background produced the unusual combination of extreme ABA resistance and desiccation tolerance, creating an opportunity to separate the underlying biochemical characteristics of ABA sensitivity and desiccation tolerance that we investigated by quantitative proteomics. Our analysis identified at least three-fold more differentially accumulated seed proteins than previous studies. Comparison of dry seed proteomes of the different genotypes allowed us to separate and refine the changes in protein accumulation patterns correlating with desiccation tolerance independently of ABA sensitivity, orvice versa, to a subset of cold-induced and defense stress-responsive proteins and signaling regulators.

Summary Sentence

Extreme ABA resistance conferred by overexpression of AFP2 is not mediated by interactions with E3 ligases, but thedwabackground maintains desiccation tolerance despite ABA resistance.
Monospecific and bispecific monoclonal SARS-CoV-2 neutralizing antibodies that maintain potency against B.1.617
Authors: Peng Lei , Hu Yingxia , Mankowski Madeleine C. , Ren Ping , Chen Rita E. , Wei Jin , Zhao Min , Li Tongqing , Tripler Therese , Ye Lupeng , Chow Ryan D. , Fang Zhenhao , Wu Chunxiang , Dong Matthew B. , Cook Matthew , Wang Guilin , Clark Paul , Nelson Bryce , Klein Daryl , Sutton Richard , Diamond Michael S. , Wilen Craig B. , Xiong Yong , Chen Sidi
Published: December 2021

COVID-19 pathogen SARS-CoV-2 has infected hundreds of millions and caused over 5 million deaths to date. Although multiple vaccines are available, breakthrough infections occur especially by emerging variants. Effective therapeutic options such as monoclonal antibodies (mAbs) are still critical. Here, we report the development, cryo-EM structures, and functional analyses of mAbs that potently neutralize SARS-CoV-2 variants of concern. By high-throughput single cell sequencing of B cells from spike receptor binding domain (RBD) immunized animals, we identified two highly potent SARS-CoV-2 neutralizing mAb clones that have single-digit nanomolar affinity and low-picomolar avidity, and generated a bispecific antibody. Lead antibodies showed strong inhibitory activity against historical SARS-CoV-2 and several emerging variants of concern. We solved several cryo-EM structures at ∼3 Å resolution of these neutralizing antibodies in complex with prefusion spike trimer ectodomain, and revealed distinct epitopes, binding patterns, and conformations. The lead clones also showed potent efficacy in vivo against authentic SARS-CoV-2 in both prophylactic and therapeutic settings. We also generated and characterized a humanized antibody to facilitate translation and drug development. The humanized clone also has strong potency against both the original virus and the B.1.617.2 Delta variant. These mAbs expand the repertoire of therapeutics against SARS-CoV-2 and emerging variants.
PMRT1, aPlasmodiumspecific parasite plasma membrane transporter is essential for asexual and sexual blood stage development
Authors: Wichers Jan Stephan , Mesén-Ramírez Paolo , Fuchs Gwendolin , Yu-Strzelczyk Jing , Stäcker Jan , von Thien Heidrun , Alder Arne , Henshall Isabelle , Liffner Benjamin , Nagel Georg , Löw Christian , Wilson Danny , Spielmann Tobias , Gao Shiqiang , Gilberger Tim-Wolf , Bachmann Anna , Strauss Jan
Published: December 2021

Membrane transport proteins perform crucial roles in cell physiology. The obligate intracellular parasitePlasmodium falciparum, an agent of human malaria, relies on membrane transport proteins for the uptake of nutrients from the host, disposal of metabolic waste, exchange of metabolites between organelles and generation and maintenance of transmembrane electrochemical gradients for its growth and replication within human erythrocytes. Despite their importance forPlasmodiumcellular physiology, the functional roles of a number of membrane transport proteins remain unclear, which is particularly true for orphan membrane transporters that have no or limited sequence homology to transporter proteins in other evolutionary lineages. Therefore, in the current study, we applied endogenous tagging, targeted gene disruption, conditional knockdown and knockout approaches to investigate the subcellular localization and essentiality of six membrane transporters during intraerythrocytic development ofP. falciparumparasites. They are localized at different subcellular structures – the food vacuole, the apicoplast, and the parasite plasma membrane – and four out of the six membrane transporters are essential during asexual development. Additionally, the plasma membrane resident transporter 1 (PMRT1, PF3D7_1135300), a uniquePlasmodium-specific plasma membrane transporter, was shown to be essential for gametocytogenesis and functionally conserved within the genusPlasmodium. Overall, we reveal the importance of four orphan transporters to blood stageP. falciparumdevelopment, which have diverse intracellular localizations and putative functions.

Importance

Plasmodium falciparum-infected erythrocytes possess multiple compartments with designated membranes. Transporter proteins embedded in these membranes do not only facilitate movement of nutrients, metabolites and other molecules between these compartments, but are common therapeutic targets and can also confer antimalarial drug resistance. Orphan membrane transporter inP. falciparumwithout sequence homology to transporters in other evolutionary lineages and divergent to host transporters may constitute attractive targets for novel intervention approaches. Here, we localized six of these putative transporters at different subcellular compartments and probed into their importance during asexual parasite growth using reverse genetic approaches. In total, only two candidates turned out to be dispensable for the parasite, highlighting four candidates as putative targets for therapeutic interventions. This study reveals the importance of several orphan transporters to blood stageP. falciparumdevelopment.
Omicron outbreak at a private gathering in the Faroe Islands, infecting 21 of 33 triple-vaccinated healthcare workers
Authors: Helmsdal Gunnhild , Hansen Olga K , Møller Lars F , Christiansen Debes H , Petersen Maria Skaalum , Kristiansen Marnar F
Published: December 2021

There are concerns that the SARS-CoV-2 Omicron variant evades immune responses due to unusually high numbers of mutations on the spike protein. Here we report a super-spreading event of Omicron infections amongst triple-vaccinated healthcare workers, infecting 21 of 33 attending a private gathering in the Faroe Islands.