bluuebunny/crossref_metadata_2025 huggingface dataset:
Discovery of ER-localized sugar transporters for cellulase production with lac1 being essential
Authors: Wang Haiyan , Pang Ai-Ping , Wang Wei , Li Bingzhi , Li Chengcheng , Wu Fu-Gen , Lin Fengming
Published: November 2022

Background

In the process of cellulose hydrolysis, carbohydrate hydrolysates are transported into cells through membrane transporters, and then affect the expression of cellulase-encoding genes. Sugar transporters play a crucial role in cellulase production in lignocellulolytic fungi, of which relatively few have been functionally validated to date and are all reported to be on cell membrane.

Result

Through transcriptome analysis and qRT-PCR, three putative MFS sugar transporters GST, MFS, and LAC1 were found to display significantly higher mRNA levels in T. reesei grown on cellulose than on glucose. The individual deletion of these three genes compromised cellulase production and delayed sugar absorption by 24 h in T. reesei. Nevertheless, they transported pretty low level of sugars, including galactose, lactose, and mannose, and did not transport glucose, when expressed in yeast system. Meanwhile, all three transporters were unexpectedly found to be intracellular, being located in endoplasmic reticulum (ER). Particularly, the knockout of lac1 almost abolished cellulase production, and significantly inhibited biomass generation regardless of sugar types, indicating that lac1 is essential for cellulase production and biomass formation. The absence of lac1 upregulated genes involved in ribosome biogenesis, while downregulated genes in cellulase production, protein processing in ER (particularly protein glycosylation), and lipid biosynthesis. The inhibition of lac1 deletion on the transcriptional levels of genes related to cellulase biosynthesis was restored after 72 h, but the cellulase production was still inhibited, indicating lac1 might pose a post-transcription regulation on cellulase production that are independent on the known cellulase regulation mediated by CRT1 and XYR1.

Conclusion

For the first time, intracellular sugar transporters (mfs, gst, and lac1) facilitating cellulase production were identified, which was distributed in ER. Their sugar transporting ability was very weak, indicating that they might be related to sugar utilization inside cells rather than the cellular sugar uptake. More importantly, sugar transporter lac1 is first found to be essential for cellulase production and biomass formation by affecting protein processing in ER (particularly protein glycosylation) and lipid biosynthesis. The effect of LAC1 on cellulase production seems to be post-transcriptional at late stage of cellulase production, independent on the well-known cellulase regulation mediated by CRT1 and XYR1. These findings improve the understanding of intracellular sugar transporters in fungi and their important role in cellulase synthesis.
Interactions between Glossina pallidipes salivary gland hypertrophy virus and tsetse endosymbionts in wild tsetse populations
Authors: Dieng Mouhamadou M. , Augustinos Antonios A. , Demirbas-Uzel Güler , Doudoumis Vangelis , Parker Andrew G. , Tsiamis George , Mach Robert L. , Bourtzis Kostas , Abd-Alla Adly M. M.
Published: November 2022

Background

Tsetse control is considered an effective and sustainable tactic for the control of cyclically transmitted trypanosomosis in the absence of effective vaccines and inexpensive, effective drugs. The sterile insect technique (SIT) is currently used to eliminate tsetse fly populations in an area-wide integrated pest management (AW-IPM) context in Senegal. For SIT, tsetse mass rearing is a major milestone that associated microbes can influence. Tsetse flies can be infected with microorganisms, including the primary and obligate Wigglesworthia glossinidia, the commensal Sodalis glossinidius, and Wolbachia pipientis. In addition, tsetse populations often carry a pathogenic DNA virus, the Glossina pallidipes salivary gland hypertrophy virus (GpSGHV) that hinders tsetse fertility and fecundity. Interactions between symbionts and pathogens might affect the performance of the insect host.

Methods

In the present study, we assessed associations of GpSGHV and tsetse endosymbionts under field conditions to decipher the possible bidirectional interactions in different Glossina species. We determined the co-infection pattern of GpSGHV and Wolbachia in natural tsetse populations. We further analyzed the interaction of both Wolbachia and GpSGHV infections with Sodalis and Wigglesworthia density using qPCR.

Results

The results indicated that the co-infection of GpSGHV and Wolbachia was most prevalent in Glossina austeni and Glossina morsitans morsitans, with an explicit significant negative correlation between GpSGHV and Wigglesworthia density. GpSGHV infection levels > 103.31 seem to be absent when Wolbachia infection is present at high density (> 107.36), suggesting a potential protective role of Wolbachia against GpSGHV.

Conclusion

The result indicates that Wolbachia infection might interact (with an undefined mechanism) antagonistically with SGHV infection protecting tsetse fly against GpSGHV, and the interactions between the tsetse host and its associated microbes are dynamic and likely species specific; significant differences may exist between laboratory and field conditions.

Graphical Abstract
The coevolution between APOBEC3 and retrotransposons in primates
Authors: Modenini Giorgia , Abondio Paolo , Boattini Alessio
Published: November 2022

Retrotransposons are genetic elements with the ability to replicate in the genome using reverse transcriptase: they have been associated with the development of different biological structures, such as the Central Nervous System (CNS), and their high mutagenic potential has been linked to various diseases, including cancer and neurological disorders. Throughout evolution and over time, Primates and Homo had to cope with infections from viruses and bacteria, and also with endogenous retroelements. Therefore, host genomes have evolved numerous methods to counteract the activity of endogenous and exogenous pathogens, and the APOBEC3 family of mutators is a prime example of a defensive mechanism in this context.

In most Primates, there are seven members of the APOBEC3 family of deaminase proteins: among their functions, there is the ability to inhibit the mobilization of retrotransposons and the functionality of viruses. The evolution of the APOBEC3 proteins found in Primates is correlated with the expansion of two major families of retrotransposons, i.e. ERV and LINE-1.

In this review, we will discuss how the rapid expansion of the APOBEC3 family is linked to the evolution of retrotransposons, highlighting the strong evolutionary arms race that characterized the history of APOBEC3s and endogenous retroelements in Primates. Moreover, the possible role of this relationship will be assessed in the context of embryonic development and brain-associated diseases.
Corporate social responsibility. A strategy for social and territorial sustainability
Authors: Carrera Letizia
Published: November 2022

Globalization and financial processes have progressively generated an intense and problematic phenomenon of disconnection between companies and their territories. Breaking of the spatial link has often led to the breaking of the social bond and the rupture of territorial cohesion.

In order to counteract this process of progressive lack of solidarity and social trust between companies and territorial communities, a very important role can be played by Corporate Social Responsibility. From few decades the European and the national reflection was focused on “Corporate Social Responsibility” considered a fundament strategy able to activate the (re) construction of new forms of solidarity and to create favorable conditions for social and economic sustainable growth, restoring continuity between activities and long-term effects connected to them. In this perspective, the corporate territorial welfare is its empirical expression, and a strategic tool to achieve the goal of counteract social and geographical peripherality to guarantee a polycentric and sustainable development of territories and highest level of quality of life of local communities.

To grasp this new type of relationship that companies can establish with “their” territories starting from their choices of welfare, different models of corporate welfare introduced in some companies in Puglia have been analyzed. A specific attention has been dedicated to the particular form of corporate welfare extended to the territory and therefore to territorial stakeholders. These actions, when present, go well beyond the most classic attention to employees, and can be considered opportunities to give shape or rebuild the most direct link with the territories. In order to investigate the corporates’ welfare choices, we have used a qualitative methodology interviewing the human resources managers of several Apulian companies and asking them about welfare choices.

From the analysis carried out it has been possible to define a typology of enterprises in relation to the adopted model of welfare.

The objective that we intend to pursue with this ongoing research is to define a kind of open catalogue of good practices that can facilitate the choices of companies to adhere to innovative forms of corporate and territorial welfare.
Comprehensive analysis to identify pseudogenes/lncRNAs-hsa-miR-200b-3p-COL5A2 network as a prognostic biomarker in gastric cancer
Authors: Li Peiyuan , Ji Wenbin , Wei Zhiwang , Wang Xiulan , Qiao Gangjie , Gao Chao , Wang Yifan , Qi Feng
Published: November 2022

Objective

Gastric cancer is one of the most common and deadly types of cancer. The molecular mechanism of gastric cancer progression remains unclear.

Materials and methods

Four hub genes were identified through GEO and TCGA database screening and analysis. Prognostic analysis revealed that COL5A2 was the most likely to affect the prognosis of gastric cancer among the four hub genes. The relationships between COL5A2 and clinical variables and immune cell infiltration were analyzed. Then, COL5A2 was analyzed for single-gene differences and related functional enrichment. Using the starBase database for prediction and analysis, miRNAs and pseudogenes/lncRNAs that might combine with COL5A2 were identified; thus, the ceRNA network was constructed. Finally, the network was verified by Cox analysis and qPCR, and a nomogram was constructed.

Results

First, we found that COL5A2, COL12A1, BGN and THBS2 were highly expressed in gastric cancer. COL5A2 had statistical significance in overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) analysis. Immune infiltration analysis suggested that COL5A2 might influence the changes in the tumor immune microenvironment. The StarBase database was used to predict that 3 pseudogenes and 7 lncRNAs might inhibit the hsa-miR-200b-3p-COL5A2 axis in gastric cancer. The pseudogenes/lncRNA-hsa-miR-200b-3p-COL5A2 ceRNA network was identified and verified using Cox regression analysis and PCR. Finally, we constructed a nomogram.

Conclusions

We elucidated the regulatory role of the pseudogenes/lncRNA-hsa-miR-200b-3p-COL5A2 network in gastric cancer progression and constructed a nomogram. These studies may provide effective treatments and potential prognostic biomarkers for gastric cancer.
Impact of COPD on clinical and CT characteristics of COVID-19-associated pneumonia: single tertiary center experience
Authors: Filippenko Yevgeniya , Zagurovskaya Marianna , Abdrakhmanova Aigul , Kassenova Saule , Zhakenova Zhanar , Aimakhanova Aizat , Zholdybay Zhamilya
Published: November 2022

Background

The severe acute respiratory syndrome-related coronavirus 2 pandemic continues to this day worldwide. Individuals with COPD are at increased risk of contracting SARS-CoV-2. Most of the conducted studies are based on the clinical assessment of COVID-19 infection with different comorbidities. The specific contribution of COPD to the severity of the disease and outcome still remains the point of investigation. The main goals of our study are to assess COPD’s influence on the severity of clinical and CT characteristics of COVID-19 pneumonia and associated in-hospital mortality.

Results

This is a retrospective study on 281 patients with RT-PCR-confirmed COVID-19 infection and CT spectrum of COVID-19 pneumonia. Fifty patients have COPD based on CT criteria. No significant difference was observed in the mean hospital length of stay, arterial oxygen saturation on admission or in-hospital mortality between COPD and non-COPD groups. Patients with COPD were two times less likely to have fever less than 37.9 °C (RR = 2.037; 95% CI 1.114–3.724, p = 0.016), but higher absolute neutrophil count (p = 0.033) and median level of neutrophil/lymphocyte ratio (p = 0.029). The COPD group was presented with milder CT severity score (especially CT1, less than 25% of lung involvement) (p = 0.022), less likely to have bilateral (RR = 2.601; 95% CI: 1.341–5.044, p = 0.023) or central (RR = 1.754; 95% CI 1.024–3.003, p = 0.046) distribution of ground-glass opacities, right lower lobe (RR = 2.887; 95% CI 1.574–5.293, p = 0.008) or left lung (RR = 2.627; 95% CI 1.448–4.765, p = 0.009) involvement, and “crazy-paving” pattern (RR = 2.208; 95% CI 1.292–3.774, p = 0.003). Both moderate positive and negative relationship was observed between CT1, CT4, hypoxia and in-hospital mortality in the COPD group (r = − 0.383, p = 0.033; r = 0.486, p = 0.007; r = − 0,354, p = 0,022, respectively).

Conclusion

The presence of COPD by imaging criteria in the settings of COVID-19-associated pneumonia did not significantly influence the clinical or imaging performance of the patients, nor was it linked to the increased in-hospital mortality.
Identification and antibiotic susceptibility evaluation of Mycoplasma synoviae isolated from chickens in central China
Authors: Wang Chun , Zhou Naiji , Liu Haopeng , Yang Rongkun , Cui Weitao , Xu Qingrong , Xiao Yuncai , Hu Sishun , Zhou Rui , Li Zili , Zhou Zutao
Published: November 2022

Mycoplasma synoviae (M. synoviae) infections have become an increasingly serious concern in China because they cause huge economic losses to the poultry industry. Antibiotic treatment is one of control strategies that can be used to contain clinical outbreaks in M. synoviae-free flocks, especially because the bacteria can be transmitted through eggs. To understand M. synoviae infection status in farms of central China and the antibiotic susceptibility of the circulating strains in vivo and in vitro, 485 samples were collected from five provinces from 2019 to 2021. Fifty-two strains were isolated and identified. Determination of the minimum inhibitory concentration (MIC) of eight antibiotics (tylvalosin, tiamulin, tilmicosin, lincomycin, enrofloxacin, chlortetracycline, doxycycline and tylosin) for isolates showed that tylvalosin, doxycycline and tiamulin were effective against 52 clinical isolates (MIC values ≤ 0.0625–0.25 μg/mL, ≤0.0625–1 μg/mL, and 0.25–2 μg/mL, respectively). Tilmicosin, enrofloxacin and lincomycin had high MIC90 values (>32 μg/mL). An artificial M. synoviae infection model was established in chickens for evaluation of the short-term therapeutic effect of these antibiotics. After 5 days of medication, doxycycline (200 mg/L) showed a superior ability to inhibit M. synoviae compared with other groups, as did tylvalosin (200 mg/L). Furthermore, the therapeutic efficacy of tylvalosin (0.4 μg/mL) on intra-embryo-injected M. synoviae was higher than that of tiamulin at the same dose. A combination of MIC values determined in vitro and therapeutic effects observed in vivo revealed that tylvalosin and doxycycline had the best therapeutic effects. Tylvalosin also showed better inhibitory effects on the vertical transmission of M. synoviae than tiamulin.
Implementation of the Time-to-Event Continuous Reassessment Method Design in a Phase I Platform Trial Testing Novel Radiotherapy-Drug Combinations—CONCORDE
Authors: Walker Katrina , Hinsley Samantha , Phillip Rachel , Oughton Jamie B. , Murden Geraldine , Chalmers Anthony J. , Faivre-Finn Corinne , Greystoke Alastair , Brown Sarah R. ,   on behalf of the CONCORDE Investigators
Published: November 2022

PURPOSE

CONCORDE is the first phase I drug-radiotherapy (RT) combination platform in non–small-cell lung cancer, designed to assess multiple different DNA damage response inhibitors in combination with radical thoracic RT. Time-to-event continuous reassessment method (TiTE-CRM) methodology will inform dose escalation individually for each different DNA damage response inhibitor-RT combination and a randomized calibration arm will aid attribution of toxicities. We report in detail the novel statistical design and implementation of the TiTE-CRM in the CONCORDE trial.

METHODS

Statistical parameters were calibrated following recommendations by Lee and Cheung. Simulations were performed to assess the operating characteristics of the chosen models and were written using modified code from the R package dfcrm.

RESULTS

The results of the simulation work showed that the proposed statistical model setup can answer the research questions under a wide range of potential scenarios. The proposed models work well under varying levels of recruitment and with multiple adaptations to the original methodology.

CONCLUSION

The results demonstrate how TiTE-CRM methodology may be used in practice in a complex dose-finding platform study. We propose that this novel phase I design has potential to overcome some of the logistical barriers that for many years have prevented timely development of novel drug-RT combinations.
Germline Variants in DNA Damage Repair Genes andHOXB13Among Black Patients With Early-Onset Prostate Cancer
Authors: Trendowski Matthew R. , Sample Christopher , Baird Tara , Sadeghpour Azita , Moon David , Ruterbusch Julie J. , Beebe-Dimmer Jennifer L. , Cooney Kathleen A.
Published: November 2022

PURPOSE

Genetic studies of prostate cancer susceptibility have predominantly focused on non-Hispanic White men, despite the observation that Black men are more likely to develop prostate cancer and die from the disease. Therefore, we sought to identify genetic variants in Black patients diagnosed with early-onset prostate cancer.

METHODS

Whole-exome sequencing of germline DNA from a population-based cohort of Black men diagnosed with prostate cancer at age 62 years or younger was performed. Analysis was focused on a panel of DNA damage repair (DDR) genes and HOXB13. All discovered variants were ranked according to their pathogenic potential based upon REVEL score, evidence from existing literature, and prevalence in the cohort. Logistic regression was used to investigate associations between mutation status and relevant clinical characteristics.

RESULTS

Among 743 Black prostate cancer patients, we identified 26 unique pathogenic (P) or likely pathogenic (LP) variants in 14 genes (including HOXB13, BRCA1/2, BRIP1, ATM, CHEK2, and PALB2) among 30 men, or approximately 4.0% of the patient population. We also identified 33 unique variants of unknown significance in 16 genes among 39 men. Because of the rarity of these variants in the population, most associations between clinical characteristics did not achieve statistical significance. However, our results suggest that carriers for P or LP (P/LP) variants were more likely to have a first-degree relative diagnosed with DDR gene-associated cancer, have a higher prostate-specific antigen at time of diagnosis, and be diagnosed with metastatic disease.

CONCLUSION

Variants in DDR genes and HOXB13 may be important cancer risk factors for Black men diagnosed with early-onset prostate cancer, and are more frequently observed in men with a family history of cancer.
The anyonic recovery of parity-time symmetry in coupled circuits system
Authors: Liu Xin-Chang , Sun Dan-Dan , Shi Xiao-Dong , Zhang Xiao-Lei , Zhang Qi , Xin Xiang-Jun
Published: November 2022

Hermiticity is the fundamental property of the physical systems, for which it should obey the laws of energy conservation and time-reversal symmetry. Parity-time symmetry is introduced to study the non-Hermitian system with real energy spectra. Considering the coupling dissipation of the practical system, there would be phase-related terms on the non-diagonal elements of the Hermitian matrix. Here in this work, we present a coupled circuit model of the system and investigate the dynamics of parity-time-anyonic Hamiltonian related to an arbitrary phase of the system. We find that parity-time symmetry can be achieved under the tunable phases in the quasi-parity-time symmetric circuit system.
Pituitary Apoplexy With Transition to Acute Hypophysitis in a Patient With Sars-CoV-2 Pneumonia
Authors: Racca Giulia , D’Agnano Salvatore , Fasano Nicoletta , Gianotti Laura
Published: November 2022

COVID-19 is a systemic disease associated with respiratory insufficiency, systemic inflammation, as well as coagulation, neurological, and endocrine disorders. Among them pituitary apoplexy (PA) as well as, more rarely, acute hypophysitis (AH) have been reported. In the present report, we described a case of PA in an 84-year-old man with SARS-CoV-2 pneumonia, with a previous unknown pituitary adenoma and a possible but not confirmed overlap with transitory AH. After reviewing the available literature, we discuss the potential clinical and pathophysiological relationship between PA and AH. Furthermore, we focus on the neuroradiological features of pituitary lesions in the presence of SARS-CoV-2 infection.
Dysglycemia With Impaired Insulin Secretion After Resection of a High-Molecular-Weight IGF-II–Producing Tumor
Authors: Shimada Yasuho , Yamashita Koh , Fukuda Izumi , Aizawa Toru
Published: November 2022

Analysis of insulin and related glucoregulatory hormone secretion following high-molecular-weight insulin-like growth factor II (HMW-IGF-II)–releasing tumor excision has never been reported. In a man with chronic hypoglycemia—plasma glucose (PG), 2.1 mmol/L with undetectable serum insulin, less than 7.2 pmol/L on admission—the cause of the hypoglycemia was HMW-IGF-II in the serum secreted by an intrathoracic benign pleural solitary fibrous tumor (size: 15 × 17 × 12 cm). Removal of the tumor nullified serum HMW-IGF-II and hypoglycemia. Postoperative glucose metabolism was evaluated day 272 by 75 g oral glucose tolerance test (OGTT) and on days 5, 202, and 990 by fasted sampling. Glycated hemoglobin A1c (HbA1c) was 37 to 41 mmol/mol, fasting PG was 5.3 to 5.4 mmol/L, and 2-hour PG at 75 g OGTT was 6.9 mmol/L, indicating that he was at the prediabetes stage. Homeostasis Model Assessment 2 of Insulin Resistance and Homeostasis Model Assessment 2 of β-Cell levels were within the normal range but the Stumvoll first phase was lowered. Insulin sensitivity and secretion were compared to age-, sex-, and body mass index–matched controls with normal glucose metabolism. Long-term HMW-IGF-II exposure of pancreatic islet β cells caused the functional impairment, that is, suppressed glucose-stimulated insulin secretion (GSIS), leading to nondiabetic hyperglycemia. This fact suggests long-term HMW-IGF-II exposure of the islet β cell specifically dampens GSIS.
MEN1 in a Patient With Nonsyndromic Familial Nonmedullary Thyroid Carcinoma
Authors: Fitzgerald Lauren A , Williamson Shelley , Shakil Jawairia , Robbins Richard J
Published: November 2022

Clinical syndromes involving multiple endocrine glands have been well recognized for over a century. Multiple reports describing hereditary multiple endocrine neoplasia (MEN) syndromes involving pituitary, parathyroid, and pancreatic neuroendocrine tumors have been published. Differentiated (nonmedullary) thyroid cancer can also present as a hereditary syndrome with or without a specific genetic predisposition. We report the case of a man with nonsyndromic familial nonmedullary thyroid carcinoma, a pituitary adenoma, hyperparathyroidism, an adrenal adenoma, and pancreatic adenocarcinoma. Genetic testing did not reveal mutations in the commonly reported genes associated with MEN syndromes. MEN1 is characterized by endocrine neoplasia in at least 2 of the following glands: pituitary, parathyroid, and the gastro-entero-pancreatic (GEP) tract. Co-occurrence of MEN1 with familial nonmedullary thyroid carcinoma, however, has not been reported in the medical literature. This unique case of MEN1 co-existing in a patient with nonsyndromic familial thyroid carcinoma was not associated with any common MEN syndrome germline mutations.
The origins of skin diversity: lessons from dermal fibroblasts
Authors: Myung Peggy , Andl Thomas , Atit Radhika
Published: November 2022

Skin is largely composed of an epidermis that overlies a supporting dermis. Recent advancements in our understanding of how diverse groups of dermal fibroblasts regulate epidermal and hair follicle growth and differentiation have been fueled by tools capable of resolving molecular heterogeneity at a single-cell level. Fibroblast heterogeneity can be traced back to their developmental origin before their segregation into spatially distinct fibroblast subtypes. The mechanisms that drive this lineage diversification during development are being unraveled, with studies showing that both large- and small-scale positional signals play important roles during dermal development. Here, we first delineate what is known about the origins of the dermis and the central role of Wnt/β-catenin signaling in its specification across anatomical locations. We then discuss how one of the first morphologically recognizable fibroblast subtypes, the hair follicle dermal condensate lineage, emerges. Leveraging the natural variation of skin and its appendages between species and between different anatomical locations, these collective studies have identified shared and divergent factors that contribute to the extraordinary diversity of skin.
Mitochondrial respiration and dynamics of in vivo neural stem cells
Authors: Petridi Stavroula , Dubal Dnyanesh , Rikhy Richa , van den Ameele Jelle
Published: November 2022

Neural stem cells (NSCs) in the developing and adult brain undergo many different transitions, tightly regulated by extrinsic and intrinsic factors. While the role of signalling pathways and transcription factors is well established, recent evidence has also highlighted mitochondria as central players in NSC behaviour and fate decisions. Many aspects of cellular metabolism and mitochondrial biology change during NSC transitions, interact with signalling pathways and affect the activity of chromatin-modifying enzymes. In this Spotlight, we explore recent in vivo findings, primarily from Drosophila and mammalian model systems, about the role that mitochondrial respiration and morphology play in NSC development and function.
Functions of neuronal Synaptobrevin in the post-Golgi transport of Rhodopsin in Drosophila photoreceptors
Authors: Yamashita Hitomi , Ochi Yuka , Yamada Yumi , Sasaki Shogo , Tago Tatsuya , Satoh Takunori , Satoh Akiko K.
Published: November 2022

Polarized transport is essential for constructing multiple plasma membrane domains in the cell. Drosophila photoreceptors are an excellent model system to study the mechanisms of polarized transport. Rab11 is the key factor regulating the post-Golgi transport of rhodopsin 1 (Rh1; also known as NinaE), a photoreceptive protein, to the rhabdomere, a photoreceptive plasma membrane. Here, we found that neuronal Synaptobrevin (nSyb) colocalizes with Rab11 on the trans-side of Golgi stacks and post-Golgi vesicles at the rhabdomere base, and nSyb deficiency impairs rhabdomeric transport and induces accumulation of Rh1 and vesicles in the cytoplasm; this is similar to the effects of Rab11 loss. These results indicate that nSyb acts as a post-Golgi SNARE toward rhabdomeres. Surprisingly, in Rab11-, Rip11- and nSyb-deficient photoreceptors, illumination enhances cytoplasmic accumulation of Rh1, which colocalizes with Rab11, Rabenosyn5, nSyb and Arrestin 1 (Arr1). Arr1 loss, but not Rab5 dominant negative (Rab5DN) protein expression, inhibits the light-enhanced cytoplasmic Rh1 accumulation. Rab5DN inhibits the generation of Rh1-containing multivesicular bodies rather than Rh1 internalization. Overall, these results indicate that exocytic Rh1 mingles with endocytosed Rh1 and is then transported together to rhabdomeres.
Unprecedented early-summer heat stress and forecast of coral bleaching on the Great Barrier Reef, 2021-2022
Authors: Spady Blake L. , Skirving William J. , Liu Gang , De La Cour Jacqueline L. , McDonald Cathy J. , Manzello Derek P.
Published: November 2022

The Great Barrier Reef (GBR) is predicted to undergo its sixth mass coral bleaching event during the Southern Hemisphere summer of 2021-2022. Coral bleaching-level heat stress over the GBR is forecast to start earlier than any previous year in the satellite record (1985-present). The National Oceanic and Atmospheric Administration (NOAA) Coral Reef Watch (CRW) near real-time satellite-based heat stress products were used to investigate early-summer sea surface temperature (SST) and heat stress conditions on the GBR during late 2021. As of 14 December 2021, values of instantaneous heat stress (Coral Bleaching HotSpots) and accumulated heat stress over a 12-week running window (Degree Heating Weeks) on the GBR were unprecedented in the satellite record. Further, 89% of GBR satellite reef pixels for this date in 2021 had a positive seven-day SST trend of greater than 0.2 degrees Celsius/week. Background temperatures (the minimum temperature over the previous 29 days) were alarmingly high, with 87% of GBR reef pixels on 14 December 2021 being greater than the maximum SST over that same 29-day period for any year from 1985-2020. The GBR is starting the 2021-2022 summer season with more accumulated heat than ever before, which could have disastrous consequences for the health, recovery, and future of this critical reef system.
A hospital-based prospective cohort study to assess the factors associated with transmission dynamics of SARS CoV-2 among healthcare workers in Delhi
Authors: Dudeja Mridu , Sharma Pragya , Islam Farzana , Shaikh Aqsa , Singh Farishta Hannah D. , Alvi Yasir , Kashyap Varun , Mariam Warisha , Das Ayan Kumar , Haque Safa Fazal , Singh Vishal Kumar , Ahmad Mohammad , Rahman Anisur
Published: November 2022

Background: Healthcare personnel providing COVID-19 care are at increased risk of acquiring infection. Understanding the factors associated with the transmission of infection among healthcare workers provides input for the development of prevention strategies. The objectives of this study were to study the adherence to Infection Prevention and Control (IPC) measures followed between different categories of healthcare workers, to estimate seroconversion rate based on the type of exposure with COVID-19 patients, and to study the association between seroconversion and IPC practices.

Methods: A prospective cohort study was conducted from December 2020 to June 2021 among the healthcare workers in two tertiary healthcare institutes selected by purposive sampling. All Healthcare workers (HCWs) participating in the clinical management or having any exposure to a laboratory-confirmed COVID-19 case were included. A total of 817 subjects were enrolled in the study. At baseline, details on IPC training and adherence along with details of the type of exposure with the COVID-19 patient were collected. The end-line visit was scheduled at 22-31 (preferably 28 days) days from the first visit for the collection of the symptom diary and end-line form. 

Results: Hand hygiene practices were found to be best among paramedics (98.0%), followed by doctors (84.5%) and nurses (90.1%). Maximum HCWs (99.5%; 99.8%; 97.1%) reported using Personal Protective Equipment (PPE) appropriately and regular availability of PPE in the hospital setting. Among the various categories of HCWs, nurses had the highest proportion (28.7%) of untrained personnel.

Conclusion: The HCWs who had contact with the surroundings of an infected patient showed higher odds of seroconversion although not statistically significant. Further, analyzing the types of PPE used, we found that the use of masks and gloves was protective in preventing infection. Strengthening IPC training through refresher training and demonstrating the correct use of PPE can enhance adherence to IPC measures.
Penta-Helix Model of E-Government in Combating Corruption in Indonesia and Malaysia: The Moderating Effect of Religiosity
Authors: Purnamasari Pupung , Amran Noor Afza , Nu'man A. Harits , Frendika Rusman , Nor Mohamad Naimi Mohamad , Ismail Mohamad Sharofi
Published: November 2022

Background: E-government is an initiative taken by governments worldwide to align the administration of their countries. Governments have utilized the internet as part of a transition into a globalized economy. This helps reduce red tape and procedures in dealing with people in government agencies. This study aims to develop an e-government model as an anti-corruption strategy by applying the Penta-helix model and religiosity as the moderating variable.

Methods: The data was gathered from government officials, representatives in business, media, academia, and NGOs, in Indonesia and Malaysia in 2021. Online questionnaires were distributed to 240 respondents from Indonesia and Malaysia. In addition, SPSS v.25 and SEM AMOS v.25 were used to analyze the data.

Results: The findings indicate that the Penta-helix elements and religiosity could help to reduce corruption in Indonesia. Meanwhile, Malaysia must increase its human resource competency and embed the religiosity element as a tool to reduce corruption.

Conclusion: Penta-helix and religious factors should be incorporated by organizations in Malaysia and Indonesia as part of their strategy in combating corruption.
Molecular survey of certain protozoan agents that cause diarrhea in children in Sudan
Authors: Adam Mosab , Shen Hongwei , Enan Khalid-A , Wang Hao , Musa Azza B. Musa , El Hussein Abdel R. , Khidir Isam M. , Ma Xuejun
Published: November 2022

Introduction

Diarrhea is a significant health problem in third world countries; identification of causative agents of diarrhea is essential to apply measures to prevent and control this disease. In addition, scant data are available regarding childhood diarrhea in Sudan. Our research aimed to determine the incidence of specific protozoan pathogens (Entameobia histolytica, Cryptosporidium spp., and Gardia lambelia) among the young (aged less than five years) in Khartoum, Sudan.

Methods

We conducted a parasitological cross-sectional survey, and stool samples from 437 patients were examined for E. histolytica, C.  parvum, and G. lambelia using a multiplex real-time PCR method.

Results

Of the 437 stool samples tested, infection with intestinal parasite was found in 155 (35.5%) cases, and co-infection was identified in 16 (3.7%) cases. G. lambelia (18.8%) and C. parvum (15.8 %) were the most frequently identified parasites, followed by E. histolytica (0.5%). The highest and lowest rates of parasitic infections were seen in the less than two years age group (32.7%), and in the 2–4-year-old group (2.7%), the male children showed higher rates of infections (23.7%) compared to females (11.7%). The incidence of protozoan infection was higher (37.7%) in the rainy season (August to December) (32.7%) in contrast with that (2.7%) in the dry season (April to June).

Discussion

Our present study demonstrated the high prevalence of G. lambelia and C. parvum in children with diarrhea in Khartoum State and the multiplex real-time technique's usefulness in disclosing pathogenic protozoal agents. Our result highlighted the necessity of developing intervention measurement and control strategies to deal with childhood parasitic diarrhea in this region.
Human vs. Automated Sales Agents: How and Why Customer Responses Shift Across Sales Stages
Authors: Adam Martin , Roethke Konstantin , Benlian Alexander
Published: November 2022

Customers in sales processes increasingly encounter automated sales agents that complement or replace human sales agents. Yet, little is known about whether, how, and why customers respond to automated agents in contrast to human agents across successive decision stages of the same sales process. Even less is known about customer responses to combinations where both agents assume distinct roles and focus on complementary tasks that are traditionally performed by only one single agent. Against this backdrop, this paper explores the influence of increasingly common sales representative types on customer decisions across sales stages. Our findings demonstrate that customer responses to automated (versus human) sales agents are not stable in sales processes and instead, shift as customers move across sales stages. What is more, the paper shows that combinations of sales agents versus single sales agents do matter, yet their differential effects depend on contextual features of the sales setting. These insights are important because vendors may assume that a certain type of sales agent is always more appreciated by customers, whereas in fact, different sales agent types bring distinct attributes to the table, and customers’ appreciation of these attributes shifts across sales stages.
The Impact of Trade Credit Provision on Retail Inventory: An Empirical Investigation Using Synthetic Controls
Authors: Chen Christopher J. , Jain Nitish , Yang S. Alex
Published: November 2022

Trade credit is an important source of short-term financing and an integrated part in supply contracts. Although a number of theories have been proposed on how trade credit could improve supply chain efficiency, causal studies on the impact of trade credit on operational decisions are scarce. In this study, we examine the impact of trade credit on inventory decisions using an empirical strategy that leverages (i) an exogenous shock imparted by the French government’s intervention to impose a ceiling on trade credit duration, (ii) a triple difference-in-differences identification strategy, and (iii) synthetic controls (SCs). By considering the 60-day ceiling coverage and SC construction requirements, we identify four French retail sectors as our main sample. Among them, in the postregulation period, the hardware retail sector firms on average exhibited a significant 16% decline in trade credit usage. Correspondingly, these firms also displayed a significant 11% decline in inventory level. In the remaining three sectors, we found mixed results in the main sample. All the four sectors, however, show consistent support for a causal link between trade credit and inventory in a subsample compiled using a stringent 90-day ceiling criterion. Collectively, our findings offer direct evidence that trade credit is an indispensable financing source for inventory procurement. Finally, in the postregulation period, the hardware retailers exhibited a 15.5% decline in revenue and 3.5% reduction in gross profit. This cautions policy makers that regulations limiting the use of trade credit may have unintended consequences on downstream firms, and may harm overall supply chain efficiency.

This paper was accepted by Vishal Gaur, operations management.

Funding: This work was supported by Indiana University Bloomington and the London Business School.

Supplemental Material: The online appendix is available at https://doi.org/10.1287/mnsc.2022.4600 .
A Theory of Irrelevant Advertising: An Agency-Induced Targeting Inefficiency
Authors: Shin Jiwoong , Shin Woochoel
Published: November 2022

Ad targeting technology has enabled a highly personalized delivery of online ads. Behind this development is the belief that better targeting will lead to more relevant ads. This paper challenges this lay belief by showing that irrelevant advertising can arise not necessarily from technological imperfection but also from the incentive problem embedded in the ad agency-advertisers relationship. We first demonstrate that the ad agency serving multiple advertisers may strategically allocate an ad impression to a lesser-matched, sometimes totally irrelevant, niche advertiser because future impressions can match better with the mainstream advertiser. We further find that, without a contractual obligation to serve both advertisers, the agency may not deliver completely irrelevant ads to consumers. However, another type of inefficiency can arise where the agency may not send any ad to potentially interested consumers who have a strictly positive match probability with advertisers. These inefficiencies arise due to contractual restrictions, either contractual obligations or budget constraints, when the agency serves multiple advertisers. As such, we endogenize the advertisers’ contractual requirement choices and show how the contractual obligation(s) can arise in equilibrium. Finally, we show that irrelevant ads will not disappear simply because more impressions are available in the market. Our analysis suggests that as the number of impressions increases, the irrelevant ads can persist, but the probability of receiving irrelevant ads decreases.

This paper was accepted by Dmitri Kuksov, marketing.

Funding: W. Shin gratefully acknowledges financial support from the Brian R. Gamache Endowed Professorship at the University of Florida.

Supplemental Material: The online appendix is available at https://doi.org/10.1287/mnsc.2022.4605 .
Conic Optimization with Spectral Functions on Euclidean Jordan Algebras
Authors: Coey Chris , Kapelevich Lea , Vielma Juan Pablo
Published: November 2022

Spectral functions on Euclidean Jordan algebras arise frequently in convex optimization models. Despite the success of primal-dual conic interior point solvers, there has been little work on enabling direct support for spectral cones, that is, proper nonsymmetric cones defined from epigraphs and perspectives of spectral functions. We propose simple logarithmically homogeneous barriers for spectral cones and we derive efficient, numerically stable procedures for evaluating barrier oracles such as inverse Hessian operators. For two useful classes of spectral cones—the root-determinant cones and the matrix monotone derivative cones—we show that the barriers are self-concordant, with nearly optimal parameters. We implement these cones and oracles in our open-source solver Hypatia, and we write simple, natural formulations for four applied problems. Our computational benchmarks demonstrate that Hypatia often solves the natural formulations more efficiently than advanced solvers such as MOSEK 9 solve equivalent extended formulations written using only the cones these solvers support.

Funding: This work was supported by Office of Naval Research [Grant N00014-18-1-2079] and the National Science Foundation [Grant OAC-1835443].
The Stability of MNL-Based Demand Under Dynamic Customer Substitution and Its Algorithmic Implications
Authors: Aouad Ali , Segev Danny
Published: November 2022

We study the dynamic assortment planning problem under the widely utilized multinomial logit choice model (MNL). In this single-period assortment optimization and inventory management problem, the retailer jointly decides on an assortment, that is, a subset of products to be offered, as well as on the inventory levels of these products, aiming to maximize the expected revenue subject to a capacity constraint on the total number of units stocked. The demand process is formed by a stochastic stream of arriving customers, who dynamically substitute between products according to the MNL model. Although this dynamic setting is extensively studied, the best known approximation algorithm guarantees an expected revenue of at least 0.139 times the optimum, assuming that the demand distribution has an increasing failure rate. In this paper, we establish novel stochastic inequalities showing that, for any given inventory level, the expected demand of each offered product is “stable” under basic algorithmic operations, such as scaling the MNL preference weights and shifting inventory across comparable products. We exploit this sensitivity analysis to devise the first approximation scheme for dynamic assortment planning under the MNL model.
Approximate Submodularity in Network Design Problems
Authors: DeValve Levi , Pekeč Saša , Wei Yehua
Published: November 2022

The paper “Approximate Submodularity in Network Design Problems” studies general network design problems where a firm strategically selects its network to better match supply and demand in the future. The paper observes that the arcs in network design problems are cover modular, i.e., approximately substitutes with each other, in the sense that local changes in the objective function can be used to bound global changes. The cover modularity is then applied to prove that a set of simple and intuitive heuristics achieve constant factor approximation guarantees in network design problems. Furthermore, the paper demonstrates cover modularity is also present in a general class of linear programming formulations.
Variations in the Corporate Social Responsibility-Performance Relationship in Emerging Market Firms
Authors: Cuervo-Cazurra Alvaro , Purkayastha Saptarshi , Ramaswamy Kannan
Published: November 2022

Corporate social responsibility (CSR) and its impact on performance have generated a debate that has evolved across several perspectives (shareholder, stakeholder, resource-based, and contingency). Building on the resource-based and contingency perspectives, we shed new light on this debate by analyzing the impact of CSR on performance in emerging market firms, advancing the idea that CSR is a mechanism that helps address market and government failures. We first argue that CSR’s three constituent dimensions (environmental, social, and governance) vary in their impact on performance because each dimension has a different mitigating effect on contextual failures that hobble emerging market firms. Specifically, we contend that social CSR has a larger effect on performance than either governance CSR or environmental CSR for emerging market firms, because the former helps build capabilities that more directly reduce the negative consequences of government failures in the provision of public goods and services that firms need to operate efficiently. We then provide additional depth to this idea by arguing that other mechanisms used for mitigating market failures in an emerging market context, namely firm-level business group affiliation and country-level government policy nudges, strengthen this differential influence of each of the three dimensions of CSR on performance. Analyses of a sample of 89 publicly traded Indian firms from 2007 to 2017 support these arguments.

Funding: A. Cuervo-Cazurra thanks the Lloyd Mullin fellowship at Northeastern University for financial support. S. Purkayastha thanks Indian Institute of Management, Calcutta for financial support.

Supplemental Material: The online appendix is available at https://doi.org/10.1287/orsc.2022.1639 .
Temperature-dependent phase-matching properties of BaGa2GeS6 in the 0.767–10.5910  µm spectral range
Authors: Kato Kiyoshi , Umemura Nobuhiro , Badikov Valeriy V. , Badikov Dmitrii V. , Petrov Valentin
Published: November 2022

We report experimental results on the temperature-dependent phase-matching properties of

B
a
G
a

2

G
e
S

6

for second-harmonic generation and sum-frequency generation in the 0.7674–10.5910 µm range. We also derive refined Sellmeier and thermo-optic dispersion formulas that provide a good reproduction of the present experimental results.